From 3935d8a2fa65140e46dc0e74bca9e5abd3b9d1f9 Mon Sep 17 00:00:00 2001 From: Inigo Date: Fri, 7 Mar 2025 09:27:56 +0000 Subject: [PATCH 01/14] First push --- .../talk2knowledgegraphs/kg_test.ipynb | 12392 ++++++++++++++++ .../subgraph_generation_sheng+inigo.ipynb | 3526 +++++ 2 files changed, 15918 insertions(+) create mode 100644 docs/notebooks/talk2knowledgegraphs/kg_test.ipynb create mode 100644 docs/notebooks/talk2knowledgegraphs/subgraph_generation_sheng+inigo.ipynb diff --git a/docs/notebooks/talk2knowledgegraphs/kg_test.ipynb b/docs/notebooks/talk2knowledgegraphs/kg_test.ipynb new file mode 100644 index 00000000..a0d7f764 --- /dev/null +++ b/docs/notebooks/talk2knowledgegraphs/kg_test.ipynb @@ -0,0 +1,12392 @@ +{ + "cells": [ + { + "cell_type": "code", + "execution_count": 1, + "id": "d351ee6b-d9da-493b-b072-1dc8380307f3", + "metadata": {}, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/oneai/miniconda3/envs/py311/lib/python3.11/site-packages/tqdm/auto.py:21: TqdmWarning: IProgress not found. Please update jupyter and ipywidgets. See https://ipywidgets.readthedocs.io/en/stable/user_install.html\n", + " from .autonotebook import tqdm as notebook_tqdm\n" + ] + } + ], + "source": [ + "# Import necessary libraries\n", + "import os\n", + "import numpy as np\n", + "import pandas as pd\n", + "import networkx as nx\n", + "import pickle\n", + "from tqdm import tqdm\n", + "from torch_geometric.utils import from_networkx\n", + "import sys\n", + "sys.path.append('../../..')\n", + "from aiagents4pharma.talk2knowledgegraphs.datasets.primekg import PrimeKG\n", + "from aiagents4pharma.talk2knowledgegraphs.datasets.starkqa_primekg import StarkQAPrimeKG\n", + "from aiagents4pharma.talk2knowledgegraphs.utils.embeddings.ollama import EmbeddingWithOllama\n", + "from aiagents4pharma.talk2knowledgegraphs.utils import kg_utils\n", + "\n", + "import matplotlib.pyplot as plt\n", + "\n", + "# # Set the logging level for httpx to WARNING to suppress INFO messages\n", + "import logging\n", + "logging.getLogger(\"httpx\").setLevel(logging.WARNING)" + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "id": "f724e7f5-1dbf-45cb-a60d-f48180b7adab", + "metadata": {}, + "outputs": [], + "source": [ + "local_dir = '../../../aiagents4pharma/talk2knowledgegraphs/tests/files/primekg_ibd_pyg_graph.pkl'" + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "id": "a6619d22-6e3e-4167-9231-acfd5a69eeaa", + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "Data(x=[3426, 768], edge_index=[2, 12752], edge_attr=[12752, 768], node_id=[3426], node_name=[3426], node_type=[3426], enriched_node=[3426], key=[12752], head_id=[12752], head_name=[12752], tail_id=[12752], tail_name=[12752], edge_type=[12752], enriched_edge=[12752])" + ] + }, + "execution_count": 3, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "with open(local_dir, 'rb') as file:\n", + " data = pickle.load(file)\n", + "\n", + "data" + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "id": "d62c7c8d-760f-44d3-9c37-ddafbd45fd3e", + "metadata": {}, + "outputs": [], + "source": [ + "G = nx.Graph()\n", + "\n", + "# Add nodes to the graph\n", + "for i in range(len(data['node_id'])):\n", + " G.add_node(\n", + " data['node_id'][i],\n", + " name=data['node_name'][i],\n", + " type=data['node_type'][i],\n", + " enriched_node=data['enriched_node'][i],\n", + " features=data['x'][i].numpy(), # You can add the node features as well\n", + " )\n", + "\n", + "# Add edges to the graph\n", + "for i in range(data['edge_index'].shape[1]): # 12752 edges\n", + " head = data['head_id'][i]\n", + " tail = data['tail_id'][i]\n", + " G.add_edge(\n", + " head,\n", + " tail,\n", + " edge_attr=data['edge_attr'][i].numpy(),\n", + " edge_type=data['edge_type'][i],\n", + " enriched_edge=data['enriched_edge'][i]\n", + " )" + ] + }, + { + "cell_type": "code", + "execution_count": 5, + "id": "53dea1e5-24b8-4705-ac23-0ef1d6f7883e", + "metadata": {}, + "outputs": [ + { + 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", + "text/plain": [ + "
" + ] + }, + "metadata": {}, + "output_type": "display_data" + } + ], + "source": [ + "first_100_nodes = list(G.nodes)[:100]\n", + "\n", + "subgraph = G.subgraph(first_100_nodes)\n", + "\n", + "plt.figure(figsize=(5, 5))\n", + "nx.draw(subgraph, with_labels=True, node_size=50, font_size=8, node_color='skyblue')\n", + "plt.title(\"Subgraph with First 100 Nodes\")\n", + "plt.show()\n" + ] + }, + { + "cell_type": "markdown", + "id": "c3cc2316-c188-45fc-ad72-80e77fcb7396", + "metadata": {}, + "source": [ + "----------" + ] + }, + { + "cell_type": "markdown", + "id": "1e3c0056-0ab0-4551-a158-b2c809d76378", + "metadata": {}, + "source": [ + "### Bert model - transforming from text to tensor" + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "id": "0273b3be-d420-4a2b-b1ca-de0a3e05e8e6", + "metadata": {}, + "outputs": [], + "source": [ + "from transformers import BertTokenizer, BertModel\n", + "from transformers import AutoTokenizer, AutoModel\n", + "import torch" + ] + }, + { + "cell_type": "code", + "execution_count": 7, + "id": "d9c7affa-2558-433d-a3b1-b5dcf31b7ccd", + "metadata": {}, + "outputs": [], + "source": [ + "tokenizer = BertTokenizer.from_pretrained('bert-base-uncased')\n", + "model = BertModel.from_pretrained('bert-base-uncased')\n", + "\n", + "def get_text_embedding(text):\n", + " inputs = tokenizer(text, return_tensors='pt', truncation=True, padding=True, max_length=256)\n", + " outputs = model(**inputs)\n", + " # Get the mean of the hidden states (contextual embeddings)\n", + " \n", + " return outputs.last_hidden_state.mean(dim=1).detach().numpy() # Shape: (1, hidden_size)\n", + "\n", + "# Example: Get embedding for a species description\n", + "text_description = \"STAT3 belongs to gene/protein category. The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2.\"\n", + "text_embedding = get_text_embedding(text_description)\n" + ] + }, + { + "cell_type": "markdown", + "id": "764bdd6c-1e62-4a42-b97d-d43644ba82d9", + "metadata": {}, + "source": [ + "### Graph behaviour" + ] + }, + { + "cell_type": "markdown", + "id": "b0e26fcb-9506-4c2e-9e9f-dfe14efa3f23", + "metadata": {}, + "source": [ + "We pass each enriched node text through the BERT model to obtain an embedding" + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "id": "e6c0fe91-e158-4fb3-aa91-d96e54ec5f88", + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "0 / 3426\n", + "1 / 3426\n", + "2 / 3426\n", + "3 / 3426\n", + "4 / 3426\n", + "5 / 3426\n", + "6 / 3426\n", + "7 / 3426\n", + "8 / 3426\n", + "9 / 3426\n", + "10 / 3426\n", + "11 / 3426\n", + "12 / 3426\n", 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"total_len = len(nodes_list)\n", + "batch_size = 100 # You can adjust this batch size for when to invoke garbage collection\n", + "\n", + "for node_idx in range(total_len):\n", + " node = nodes_list[node_idx]\n", + " print(f\"{node_idx} / {total_len}\")\n", + " \n", + " try:\n", + " if 'enriched_node' in G.nodes[node]:\n", + " text = G.nodes[node]['enriched_node']\n", + " G.nodes[node]['BERT_embedding'] = get_text_embedding(text)\n", + " else:\n", + " print(f\"Warning: 'enriched_node' not found for node {node}\")\n", + " except Exception as e:\n", + " print(f\"Error processing node {node}: {e}\")\n", + " \n", + " # Optionally, invoke garbage collection after every `batch_size` nodes processed\n", + " if node_idx % batch_size == 0 and node_idx != 0:\n", + " gc.collect() # Force garbage collection to free memory\n" + ] + }, + { + "cell_type": "markdown", + "id": "750eb21d-f40c-413e-8982-6ce0ec41d21e", + "metadata": {}, + "source": [ + "### We add neighbor embeddings" + ] + }, + { + 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neighbors N hops away (for hops 1, 2, etc.)\n", + " nodes_n_hops_away = [\n", + " neighbor for neighbor, dist in nx.single_source_shortest_path_length(G, node_name).items() \n", + " if dist == prop_idx + 1 and neighbor not in seen_nodes\n", + " ]\n", + " \n", + " # Update the seen nodes with the current level's neighbors\n", + " seen_nodes.update(nodes_n_hops_away)\n", + " \n", + " # Add the embeddings for these neighbors, weighted by proportion\n", + " for neighbor_idx in nodes_n_hops_away:\n", + " neighbor_node = G.nodes[neighbor_idx]\n", + " embedding += neighbor_node['BERT_embedding'] * proportions[prop_idx]\n", + " weight += proportions[prop_idx] # Add the weight of the current hop level\n", + "\n", + " # Normalize the final embedding by the total weight\n", + " node['FINAL_embedding'] = embedding / weight\n", + " #print(f\"Final embedding for node {node_name}: {node['FINAL_embedding']}\")\n" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "id": 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"execution_count": 10, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "na = nodes_list[1]\n", + "G.nodes[na]['BERT_embedding']" + ] + }, + { + "cell_type": "markdown", + "id": "4d2003b5-52c4-4f18-a30e-54ee4a442a99", + "metadata": {}, + "source": [ + "### Obtain most similar embedding" + ] + }, + { + "cell_type": "code", + "execution_count": 11, + "id": "143fede2-c942-4eac-a544-277f88b20479", + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "5.3094707\n", + "3.7479894\n", + "4.25238\n", + "4.854794\n", + "5.018378\n", + "5.0496874\n", + "5.6753287\n", + "4.9480615\n", + "5.195637\n", + "5.074986\n", + "5.8564906\n", + "5.570511\n", + "15.469068\n", + "7.935748\n", + "7.115003\n", + "6.4524913\n", + "22.56122\n", + "20.650793\n", + "21.559465\n", + "22.882952\n", + "11.887986\n", + "26.266844\n", + "9.679993\n", + "28.906958\n", + "9.017548\n", + "35.53873\n", + "25.933327\n", + 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= curr_emb.flatten()\n", + " text_embedding = text_embedding.flatten()\n", + " \n", + " #cosine_sim = np.dot(curr_emb, text_embedding) / (np.linalg.norm(curr_emb) * np.linalg.norm(text_embedding))\n", + " linear_sim = np.linalg.norm(curr_emb - text_embedding)\n", + " print(linear_sim)\n", + " if ((best_node is None) | (linear_sim < best_sim)):\n", + " best_node = node_name\n", + " best_sim = linear_sim" + ] + }, + { + "cell_type": "code", + "execution_count": 12, + "id": "27bee18b-e76b-43f1-9bcd-7866ffc9d394", + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "'IL10RB_(179)'" + ] + }, + "execution_count": 12, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "best_node" + ] + }, + { + "cell_type": "code", + "execution_count": 13, + "id": "542c3bb4-4a1f-4f84-850f-ca690cd1c8ad", + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "3.7479894" + ] + }, + "execution_count": 13, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "best_sim" + ] + }, + { + "cell_type": "code", + "execution_count": 14, + "id": "fecc0f76-1116-400a-a021-99f493e30ced", + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "data": { + "text/plain": [ + "{'name': 'IL10RB',\n", + " 'type': 'gene/protein',\n", + " 'enriched_node': 'IL10RB belongs to gene/protein category. The protein encoded by this gene belongs to the cytokine receptor family. It is an accessory chain essential for the active interleukin 10 receptor complex. Coexpression of this and IL10RA proteins has been shown to be required for IL10-induced signal transduction. This gene and three other interferon receptor genes, IFAR2, IFNAR1, and IFNGR2, form a class II cytokine receptor gene cluster located in a small region on chromosome 21. [provided by RefSeq, Jul 2008].',\n", + " 'features': array([ 2.47649457e-02, 2.27820016e-02, -1.69560522e-01, -3.35070789e-02,\n", + " 8.52039382e-02, -4.47765887e-02, 4.06866398e-04, 3.38708200e-02,\n", + " 8.85483692e-04, -5.48509024e-02, -2.48616599e-02, 4.08173949e-02,\n", + " 5.26165143e-02, -9.47317749e-04, 6.65599257e-02, -2.95930486e-02,\n", + " -2.54397616e-02, 1.05780065e-02, 2.82950737e-02, 3.88805866e-02,\n", + " -3.57877351e-02, -2.41180733e-02, 2.66018300e-03, 4.74014170e-02,\n", + " 1.24380529e-01, 8.75102133e-02, 2.64107957e-02, -5.74104190e-02,\n", + " -4.51339521e-02, -6.16167374e-02, 4.16413024e-02, -1.24433022e-02,\n", + " 2.79269870e-02, -5.66958301e-02, 1.06925778e-02, -2.90871635e-02,\n", + " 2.93817129e-02, -1.29560931e-02, -5.70652001e-02, 3.95376422e-02,\n", + " 3.77608836e-02, -4.29488271e-02, 3.73597853e-02, -1.16063925e-02,\n", + " 4.03282456e-02, 4.86438572e-02, 3.09612006e-02, 6.15862347e-02,\n", + " 7.20024034e-02, -1.01926383e-02, 2.76156757e-02, 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" -1.98228583e-01, -3.45591366e-01, 2.80466408e-01]], dtype=float32)}" + ] + }, + "execution_count": 14, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "G.nodes[best_node]" + ] + }, + { + "cell_type": "code", + "execution_count": 15, + "id": "1d148db1-44bc-485a-8aba-5b73f881e9f4", + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "data": { + "text/plain": [ + "{'name': 'STAT3',\n", + " 'type': 'gene/protein',\n", + " 'enriched_node': 'STAT3 belongs to gene/protein category. The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. This gene also plays a role in regulating host response to viral and bacterial infections. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. 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"language": "python", + "name": "myenv" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.11.11" + } + }, + "nbformat": 4, + "nbformat_minor": 5 +} diff --git a/docs/notebooks/talk2knowledgegraphs/subgraph_generation_sheng+inigo.ipynb b/docs/notebooks/talk2knowledgegraphs/subgraph_generation_sheng+inigo.ipynb new file mode 100644 index 00000000..95ef4710 --- /dev/null +++ b/docs/notebooks/talk2knowledgegraphs/subgraph_generation_sheng+inigo.ipynb @@ -0,0 +1,3526 @@ +{ + "cells": [ + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "# PrimeKG Subgraph Construction" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "In this tutorial, we will showcase how to construct a subraph from PrimeKG and prepare necessary graph formats for further analysis.\n", + "\n", + "In particular, we will slice a subgraph from PrimeKG related to inflammatory bowel disease (IBD).\n", + "\n", + "The subgraph will contain all nodes and edges that are connected to IBD-related disease nodes, including the following relationships:\n", + "- Disease-Protein Relationship\n", + "- Disease-Disease Relationship (skipped as of now)\n", + "- Protein-Protein Relationship (skipped as of now)\n", + "- Drug-Protein Relationship\n", + "- Pathway-Protein Relationship\n", + "- Pathway-Pathway Relationship (skipped as of now)\n", + "- Bioprocess-Protein Relationship\n", + "- Molecular Function-Protein Relationship\n", + "- Cellular Component-Protein Relationship" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "In addition, to enrich the nodes and edges, we will perform the following tasks:\n", + "- Textual enrichment (only this task is implemented as of now) \n", + "- Multi-modal enrichment (to be added)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "\n", + "First of all, we need to import necessary libraries as follows:" + ] + }, + { + "cell_type": "code", + "execution_count": 1, + "metadata": {}, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/oneai/miniconda3/envs/py311/lib/python3.11/site-packages/tqdm/auto.py:21: TqdmWarning: IProgress not found. Please update jupyter and ipywidgets. See https://ipywidgets.readthedocs.io/en/stable/user_install.html\n", + " from .autonotebook import tqdm as notebook_tqdm\n" + ] + } + ], + "source": [ + "# Import necessary libraries\n", + "import os\n", + "import numpy as np\n", + "import pandas as pd\n", + "import networkx as nx\n", + "import pickle\n", + "from tqdm import tqdm\n", + "from torch_geometric.utils import from_networkx\n", + "import sys\n", + "sys.path.append('../../..')\n", + "from aiagents4pharma.talk2knowledgegraphs.datasets.primekg import PrimeKG\n", + "from aiagents4pharma.talk2knowledgegraphs.datasets.starkqa_primekg import StarkQAPrimeKG\n", + "from aiagents4pharma.talk2knowledgegraphs.utils.embeddings.ollama import EmbeddingWithOllama\n", + "from aiagents4pharma.talk2knowledgegraphs.utils import kg_utils\n", + "\n", + "# # Set the logging level for httpx to WARNING to suppress INFO messages\n", + "import logging\n", + "logging.getLogger(\"httpx\").setLevel(logging.WARNING)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### PrimeKG" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "We utilize the `PrimeKG` class from the aiagents4pharma/talk2knowledgegraphs library.\n", + "\n", + "The `PrimeKG` needs to be initialized with the path to the PrimeKG dataset to be stored/loaded from the local directory." + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Loading nodes of PrimeKG dataset ...\n", + "Downloading node file from https://dataverse.harvard.edu/api/access/datafile/6180617\n" + ] + }, + { + "name": "stderr", + "output_type": "stream", + "text": [ + "100%|██████████| 8.89M/8.89M [00:00<00:00, 22.4MiB/s]\n" + ] + }, + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Loading edges of PrimeKG dataset ...\n", + "Downloading edge file from https://dataverse.harvard.edu/api/access/datafile/6180616\n" + ] + }, + { + "name": "stderr", + "output_type": "stream", + "text": [ + "100%|██████████| 387M/387M [00:39<00:00, 9.76MiB/s] \n" + ] + } + ], + "source": [ + "# Define primekg data by providing a local directory where the data is stored\n", + "primekg_data = PrimeKG(local_dir=\"../../../../data/primekg/\")\n", + "\n", + "# Invoke a method to load the data\n", + "primekg_data.load_data()\n", + "\n", + "# Get primekg_nodes and primekg_edges\n", + "primekg_nodes = primekg_data.get_nodes()\n", + "primekg_edges = primekg_data.get_edges()" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### IBD-related Data Filtering" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### IBD-related Disease Nodes" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "As a first step, we will perform data filtering over the primekg_nodes by querying the nodes that contains the following terms:\n", + "- inflammatory bowel disease\n", + "- crohn\n", + "- ulcerative colitis\n", + "\n", + "As of now, this basic query is used to filter the data. However, this can be replaced with a more complex query that can capture more nodes related to IBD." + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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2726927269IL21-related infantile inflammatory bowel diseaseMONDO14338disease
2815828158inflammatory bowel diseaseMONDO_grouped9960_12845_33643_11471_12831_12875_12941_13153...disease
2929329293inflammatory bowel disease, immunodeficiency, ...MONDO32601disease
3581435814Crohn ileitis and jejunitisMONDO_grouped709_21207disease
3581535815small bowel Crohn diseaseMONDO5539disease
3778437784Crohn diseaseMONDO_grouped5011_5535disease
3778537785ulcerative colitis (disease)MONDO5101disease
3901339013immune dysregulation-inflammatory bowel diseas...MONDO16542disease
3978739787immune dysregulation with inflammatory bowel d...MONDO33967disease
8377083770Crohn's colitisMONDO5532disease
9527995279Crohn jejunoileitisMONDO708disease
9528095280gastroduodenal Crohn diseaseMONDO710disease
9708897088perianal Crohn diseaseMONDO5537disease
9932599325Crohn disease of the esophagusMONDO22901disease
9968099680immune dysregulation-inflammatory bowel diseas...MONDO33968disease
9968199681inflammatory bowel disease-recurrent sinopulmo...MONDO33969disease
\n", + "
" + ], + "text/plain": [ + " node_index node_name \\\n", + "27269 27269 IL21-related infantile inflammatory bowel disease \n", + "28158 28158 inflammatory bowel disease \n", + "29293 29293 inflammatory bowel disease, immunodeficiency, ... \n", + "35814 35814 Crohn ileitis and jejunitis \n", + "35815 35815 small bowel Crohn disease \n", + "37784 37784 Crohn disease \n", + "37785 37785 ulcerative colitis (disease) \n", + "39013 39013 immune dysregulation-inflammatory bowel diseas... \n", + "39787 39787 immune dysregulation with inflammatory bowel d... \n", + "83770 83770 Crohn's colitis \n", + "95279 95279 Crohn jejunoileitis \n", + "95280 95280 gastroduodenal Crohn disease \n", + "97088 97088 perianal Crohn disease \n", + "99325 99325 Crohn disease of the esophagus \n", + "99680 99680 immune dysregulation-inflammatory bowel diseas... \n", + "99681 99681 inflammatory bowel disease-recurrent sinopulmo... \n", + "\n", + " node_source node_id \\\n", + "27269 MONDO 14338 \n", + "28158 MONDO_grouped 9960_12845_33643_11471_12831_12875_12941_13153... \n", + "29293 MONDO 32601 \n", + "35814 MONDO_grouped 709_21207 \n", + "35815 MONDO 5539 \n", + "37784 MONDO_grouped 5011_5535 \n", + "37785 MONDO 5101 \n", + "39013 MONDO 16542 \n", + "39787 MONDO 33967 \n", + "83770 MONDO 5532 \n", + "95279 MONDO 708 \n", + "95280 MONDO 710 \n", + "97088 MONDO 5537 \n", + "99325 MONDO 22901 \n", + "99680 MONDO 33968 \n", + "99681 MONDO 33969 \n", + "\n", + " node_type \n", + "27269 disease \n", + "28158 disease \n", + "29293 disease \n", + "35814 disease \n", + "35815 disease \n", + "37784 disease \n", + "37785 disease \n", + "39013 disease \n", + "39787 disease \n", + "83770 disease \n", + "95279 disease \n", + "95280 disease \n", + "97088 disease \n", + "99325 disease \n", + "99680 disease \n", + "99681 disease " + ] + }, + "execution_count": 3, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Query for nodes related to IBD\n", + "\n", + "relevant_terms = ['inflammatory bowel disease', 'crohn', 'ulcerative colitis']\n", + "query_str = \"\"\n", + "for idx in range(len(relevant_terms)): # Assuming relevant_terms is a list\n", + " if idx == 0:\n", + " query_str += f'node_name_lower.str.contains(\"{relevant_terms[idx]}\")'\n", + " else:\n", + " query_str += f'or node_name_lower.str.contains(\"{relevant_terms[idx]}\")'\n", + "\n", + "# Get the nodes related to IBD\n", + "ibd_nodes_df = primekg_nodes.copy()\n", + "ibd_nodes_df[\"node_name_lower\"] = primekg_nodes.node_name.apply(lambda x: x.lower())\n", + "ibd_nodes_df = ibd_nodes_df[ibd_nodes_df.node_type == \"disease\"].query(query_str, engine='python')\n", + "ibd_nodes_df.drop(columns=[\"node_name_lower\"], inplace=True)\n", + "ibd_nodes_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Disease-Protein Relationship\n" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Based on the nodes related to IBD, we can further capture the records containing the relationships of disease-gene/protein nodes." + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
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598878828158inflammatory bowel diseaseMONDO_grouped9960_12845_33643_11471_12831_12875_12941_13153...disease7359ADCY7NCBI113gene/proteinassociated withdisease_protein
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598879028158inflammatory bowel diseaseMONDO_grouped9960_12845_33643_11471_12831_12875_12941_13153...disease2874PRDM1NCBI639gene/proteinassociated withdisease_protein
598879137785ulcerative colitis (disease)MONDO5101disease2712CASP3NCBI836gene/proteinassociated withdisease_protein
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330447134780IRGMNCBI345611gene/protein35814Crohn ileitis and jejunitisMONDO_grouped709_21207diseaseassociated withdisease_protein
33102775022ITGAMNCBI3684gene/protein35814Crohn ileitis and jejunitisMONDO_grouped709_21207diseaseassociated withdisease_protein
33131602889TGFB1NCBI7040gene/protein29293inflammatory bowel disease, immunodeficiency, ...MONDO32601diseaseassociated withdisease_protein
33148009104INAVANCBI55765gene/protein28158inflammatory bowel diseaseMONDO_grouped9960_12845_33643_11471_12831_12875_12941_13153...diseaseassociated withdisease_protein
331494934967IL21NCBI59067gene/protein27269IL21-related infantile inflammatory bowel diseaseMONDO14338diseaseassociated withdisease_protein
\n", + "

620 rows × 12 columns

\n", + "
" + ], + "text/plain": [ + " head_index head_name head_source \\\n", + "5988787 37785 ulcerative colitis (disease) MONDO \n", + "5988788 28158 inflammatory bowel disease MONDO_grouped \n", + "5988789 37785 ulcerative colitis (disease) MONDO \n", + "5988790 28158 inflammatory bowel disease MONDO_grouped \n", + "5988791 37785 ulcerative colitis (disease) MONDO \n", + "... ... ... ... \n", + "3304471 34780 IRGM NCBI \n", + "3310277 5022 ITGAM NCBI \n", + "3313160 2889 TGFB1 NCBI \n", + "3314800 9104 INAVA NCBI \n", + "3314949 34967 IL21 NCBI \n", + "\n", + " head_id head_type \\\n", + "5988787 5101 disease \n", + "5988788 9960_12845_33643_11471_12831_12875_12941_13153... disease \n", + "5988789 5101 disease \n", + "5988790 9960_12845_33643_11471_12831_12875_12941_13153... disease \n", + "5988791 5101 disease \n", + "... ... ... \n", + "3304471 345611 gene/protein \n", + "3310277 3684 gene/protein \n", + "3313160 7040 gene/protein \n", + "3314800 55765 gene/protein \n", + "3314949 59067 gene/protein \n", + "\n", + " tail_index tail_name \\\n", + "5988787 7359 ADCY7 \n", + "5988788 7359 ADCY7 \n", + "5988789 2874 PRDM1 \n", + "5988790 2874 PRDM1 \n", + "5988791 2712 CASP3 \n", + "... ... ... \n", + "3304471 35814 Crohn ileitis and jejunitis \n", + "3310277 35814 Crohn ileitis and jejunitis \n", + "3313160 29293 inflammatory bowel disease, immunodeficiency, ... \n", + "3314800 28158 inflammatory bowel disease \n", + "3314949 27269 IL21-related infantile inflammatory bowel disease \n", + "\n", + " tail_source tail_id \\\n", + "5988787 NCBI 113 \n", + "5988788 NCBI 113 \n", + "5988789 NCBI 639 \n", + "5988790 NCBI 639 \n", + "5988791 NCBI 836 \n", + "... ... ... \n", + "3304471 MONDO_grouped 709_21207 \n", + "3310277 MONDO_grouped 709_21207 \n", + "3313160 MONDO 32601 \n", + "3314800 MONDO_grouped 9960_12845_33643_11471_12831_12875_12941_13153... \n", + "3314949 MONDO 14338 \n", + "\n", + " tail_type display_relation relation \n", + "5988787 gene/protein associated with disease_protein \n", + "5988788 gene/protein associated with disease_protein \n", + "5988789 gene/protein associated with disease_protein \n", + "5988790 gene/protein associated with disease_protein \n", + "5988791 gene/protein associated with disease_protein \n", + "... ... ... ... \n", + "3304471 disease associated with disease_protein \n", + "3310277 disease associated with disease_protein \n", + "3313160 disease associated with disease_protein \n", + "3314800 disease associated with disease_protein \n", + "3314949 disease associated with disease_protein \n", + "\n", + "[620 rows x 12 columns]" + ] + }, + "execution_count": 4, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# IBD disease_protein edges\n", + "ibd_disease_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_index.isin(ibd_nodes_df.index.values)) & \n", + " (primekg_edges.tail_type == 'gene/protein')],\n", + " primekg_edges[(primekg_edges.tail_index.isin(ibd_nodes_df.index.values)) & \n", + " (primekg_edges.head_type == 'gene/protein')]])\n", + "\n", + "# Check dataframe\n", + "ibd_disease_protein_edges_df" + ] + }, + { + "cell_type": "code", + "execution_count": 5, + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "array([ 144, 179, 192, 279, 417, 625, 657, 729, 772,\n", + " 989, 1004, 1122, 1299, 1480, 1567, 1618, 1654, 1777,\n", + " 1990, 2012, 2057, 2078, 2111, 2139, 2329, 2384, 2543,\n", + " 2643, 2712, 2749, 2874, 2889, 2978, 2983, 3064, 3088,\n", + " 3233, 3259, 3333, 3414, 3460, 3469, 3474, 3484, 3495,\n", + " 3578, 3646, 4152, 4162, 4731, 4818, 4968, 4997, 5022,\n", + " 5195, 5385, 5720, 5805, 5915, 6168, 6175, 6229, 6428,\n", + " 6661, 7059, 7083, 7359, 7384, 7899, 7958, 8030, 8564,\n", + " 9104, 9454, 9763, 10113, 10191, 10919, 11103, 11134, 11199,\n", + " 11523, 11588, 12305, 12663, 12740, 12763, 12816, 13014, 13365,\n", + " 21972, 22105, 34623, 34776, 34777, 34778, 34779, 34780, 34781,\n", + " 34814, 34887, 34967, 35156])" + ] + }, + "execution_count": 5, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Get unique protein index\n", + "ibd_protein_index = np.unique(np.concatenate([ibd_disease_protein_edges_df[ibd_disease_protein_edges_df.head_type == 'gene/protein'].head_index.unique(),\n", + " ibd_disease_protein_edges_df[ibd_disease_protein_edges_df.tail_type == 'gene/protein'].tail_index.unique()]))\n", + "ibd_protein_index" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Disease-Disease Relationship" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Here, we can get the records containing the relationships of disease-disease nodes." + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "metadata": {}, + "outputs": [], + "source": [ + "# # IBD disease_disease edges \n", + "# ibd_disease_disease_edges_df = pd.concat([primekg_edges[(primekg_edges.head_index.isin(ibd_nodes_df.index.values)) & \n", + "# (primekg_edges.tail_type == 'disease')],\n", + "# primekg_edges[(primekg_edges.tail_index.isin(ibd_nodes_df.index.values)) & \n", + "# (primekg_edges.head_type == 'disease')]])\n", + "\n", + "# # Check dataframe\n", + "# ibd_disease_disease_edges_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Protein-Protein Relationship" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "We also can get the records containing the relationships of gene/protein-gene/protein nodes." + ] + }, + { + "cell_type": "code", + "execution_count": 7, + "metadata": {}, + "outputs": [], + "source": [ + "# # IBD protein_protein edges \n", + "# ibd_protein_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_index.isin(ibd_protein_index)) & \n", + "# (primekg_edges.tail_type == 'gene/protein')],\n", + "# primekg_edges[(primekg_edges.tail_index.isin(ibd_protein_index)) & \n", + "# (primekg_edges.head_type == 'gene/protein')]])\n", + "\n", + "# # Check dataframe\n", + "# ibd_protein_protein_edges_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Drug-Protein Relationship" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Next, we will get the records containing the relationships of drug-gene/protein nodes." + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
32175914118Rose bengalDrugBankDB11182drug3233LTFNCBI4057gene/proteincarrierdrug_protein
32176314038Fluticasone furoateDrugBankDB08906drug4152ABCB1NCBI5243gene/proteincarrierdrug_protein
32176414555Technetium Tc-99m tetrofosminDrugBankDB09160drug4152ABCB1NCBI5243gene/proteincarrierdrug_protein
32176514040FluticasoneDrugBankDB13867drug4152ABCB1NCBI5243gene/proteincarrierdrug_protein
32237314060LevothyroxineDrugBankDB00451drug4152ABCB1NCBI5243gene/proteinenzymedrug_protein
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57316394152ABCB1NCBI5243gene/protein14498RisdiplamDrugBankDB15305drugtransporterdrug_protein
57316404152ABCB1NCBI5243gene/protein14908UbrogepantDrugBankDB15328drugtransporterdrug_protein
57316414152ABCB1NCBI5243gene/protein14499ElexacaftorDrugBankDB15444drugtransporterdrug_protein
57316424152ABCB1NCBI5243gene/protein14050Prednisolone acetateDrugBankDB15566drugtransporterdrug_protein
57316434152ABCB1NCBI5243gene/protein15752SelpercatinibDrugBankDB15685drugtransporterdrug_protein
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2030 rows × 12 columns

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" + ], + "text/plain": [ + " head_index head_name head_source head_id \\\n", + "321759 14118 Rose bengal DrugBank DB11182 \n", + "321763 14038 Fluticasone furoate DrugBank DB08906 \n", + "321764 14555 Technetium Tc-99m tetrofosmin DrugBank DB09160 \n", + "321765 14040 Fluticasone DrugBank DB13867 \n", + "322373 14060 Levothyroxine DrugBank DB00451 \n", + "... ... ... ... ... \n", + "5731639 4152 ABCB1 NCBI 5243 \n", + "5731640 4152 ABCB1 NCBI 5243 \n", + "5731641 4152 ABCB1 NCBI 5243 \n", + "5731642 4152 ABCB1 NCBI 5243 \n", + "5731643 4152 ABCB1 NCBI 5243 \n", + "\n", + " head_type tail_index tail_name tail_source tail_id \\\n", + "321759 drug 3233 LTF NCBI 4057 \n", + "321763 drug 4152 ABCB1 NCBI 5243 \n", + "321764 drug 4152 ABCB1 NCBI 5243 \n", + "321765 drug 4152 ABCB1 NCBI 5243 \n", + "322373 drug 4152 ABCB1 NCBI 5243 \n", + "... ... ... ... ... ... \n", + "5731639 gene/protein 14498 Risdiplam DrugBank DB15305 \n", + "5731640 gene/protein 14908 Ubrogepant DrugBank DB15328 \n", + "5731641 gene/protein 14499 Elexacaftor DrugBank DB15444 \n", + "5731642 gene/protein 14050 Prednisolone acetate DrugBank DB15566 \n", + "5731643 gene/protein 15752 Selpercatinib DrugBank DB15685 \n", + "\n", + " tail_type display_relation relation \n", + "321759 gene/protein carrier drug_protein \n", + "321763 gene/protein carrier drug_protein \n", + "321764 gene/protein carrier drug_protein \n", + "321765 gene/protein carrier drug_protein \n", + "322373 gene/protein enzyme drug_protein \n", + "... ... ... ... \n", + "5731639 drug transporter drug_protein \n", + "5731640 drug transporter drug_protein \n", + "5731641 drug transporter drug_protein \n", + "5731642 drug transporter drug_protein \n", + "5731643 drug transporter drug_protein \n", + "\n", + "[2030 rows x 12 columns]" + ] + }, + "execution_count": 8, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# IBD drug_protein edges\n", + "ibd_drug_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'drug') & \n", + " (primekg_edges.tail_type == 'gene/protein') & \n", + " (primekg_edges.tail_index.isin(ibd_protein_index))], \n", + " primekg_edges[(primekg_edges.tail_type == 'drug') & \n", + " (primekg_edges.head_type == 'gene/protein') & \n", + " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", + "\n", + "# Check dataframe\n", + "ibd_drug_protein_edges_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Pathway-Protein Relationship" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "For this case, we will get the records containing the relationships of pathway-protein nodes." + ] + }, + { + "cell_type": "code", + "execution_count": 9, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
650578462703Adherens junctions interactionsREACTOMER-HSA-418990pathway8030CDH3NCBI1001gene/proteininteracts withpathway_protein
6506102128079Regulation of actin dynamics for phagocytic cu...REACTOMER-HSA-2029482pathway2139ARPC2NCBI10109gene/proteininteracts withpathway_protein
6506103128183EPHB-mediated forward signalingREACTOMER-HSA-3928662pathway2139ARPC2NCBI10109gene/proteininteracts withpathway_protein
6506104128022RHO GTPases Activate WASPs and WAVEsREACTOMER-HSA-5663213pathway2139ARPC2NCBI10109gene/proteininteracts withpathway_protein
650610562931Clathrin-mediated endocytosisREACTOMER-HSA-8856828pathway2139ARPC2NCBI10109gene/proteininteracts withpathway_protein
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38346652543CDH1NCBI999gene/protein127731Integrin cell surface interactionsREACTOMER-HSA-216083pathwayinteracts withpathway_protein
38346662543CDH1NCBI999gene/protein127617Apoptotic cleavage of cell adhesion proteinsREACTOMER-HSA-351906pathwayinteracts withpathway_protein
38346672543CDH1NCBI999gene/protein62703Adherens junctions interactionsREACTOMER-HSA-418990pathwayinteracts withpathway_protein
38346682543CDH1NCBI999gene/protein128018RHO GTPases activate IQGAPsREACTOMER-HSA-5626467pathwayinteracts withpathway_protein
38346692543CDH1NCBI999gene/protein129039InlA-mediated entry of Listeria monocytogenes ...REACTOMER-HSA-8876493pathwayinteracts withpathway_protein
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1030 rows × 12 columns

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" + ], + "text/plain": [ + " head_index head_name \\\n", + "6505784 62703 Adherens junctions interactions \n", + "6506102 128079 Regulation of actin dynamics for phagocytic cu... \n", + "6506103 128183 EPHB-mediated forward signaling \n", + "6506104 128022 RHO GTPases Activate WASPs and WAVEs \n", + "6506105 62931 Clathrin-mediated endocytosis \n", + "... ... ... \n", + "3834665 2543 CDH1 \n", + "3834666 2543 CDH1 \n", + "3834667 2543 CDH1 \n", + "3834668 2543 CDH1 \n", + "3834669 2543 CDH1 \n", + "\n", + " head_source head_id head_type tail_index \\\n", + "6505784 REACTOME R-HSA-418990 pathway 8030 \n", + "6506102 REACTOME R-HSA-2029482 pathway 2139 \n", + "6506103 REACTOME R-HSA-3928662 pathway 2139 \n", + "6506104 REACTOME R-HSA-5663213 pathway 2139 \n", + "6506105 REACTOME R-HSA-8856828 pathway 2139 \n", + "... ... ... ... ... \n", + "3834665 NCBI 999 gene/protein 127731 \n", + "3834666 NCBI 999 gene/protein 127617 \n", + "3834667 NCBI 999 gene/protein 62703 \n", + "3834668 NCBI 999 gene/protein 128018 \n", + "3834669 NCBI 999 gene/protein 129039 \n", + "\n", + " tail_name tail_source \\\n", + "6505784 CDH3 NCBI \n", + "6506102 ARPC2 NCBI \n", + "6506103 ARPC2 NCBI \n", + "6506104 ARPC2 NCBI \n", + "6506105 ARPC2 NCBI \n", + "... ... ... \n", + "3834665 Integrin cell surface interactions REACTOME \n", + "3834666 Apoptotic cleavage of cell adhesion proteins REACTOME \n", + "3834667 Adherens junctions interactions REACTOME \n", + "3834668 RHO GTPases activate IQGAPs REACTOME \n", + "3834669 InlA-mediated entry of Listeria monocytogenes ... REACTOME \n", + "\n", + " tail_id tail_type display_relation relation \n", + "6505784 1001 gene/protein interacts with pathway_protein \n", + "6506102 10109 gene/protein interacts with pathway_protein \n", + "6506103 10109 gene/protein interacts with pathway_protein \n", + "6506104 10109 gene/protein interacts with pathway_protein \n", + "6506105 10109 gene/protein interacts with pathway_protein \n", + "... ... ... ... ... \n", + "3834665 R-HSA-216083 pathway interacts with pathway_protein \n", + "3834666 R-HSA-351906 pathway interacts with pathway_protein \n", + "3834667 R-HSA-418990 pathway interacts with pathway_protein \n", + "3834668 R-HSA-5626467 pathway interacts with pathway_protein \n", + "3834669 R-HSA-8876493 pathway interacts with pathway_protein \n", + "\n", + "[1030 rows x 12 columns]" + ] + }, + "execution_count": 9, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# IBD pathway_protein edges \n", + "ibd_pathway_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'pathway') & \n", + " (primekg_edges.tail_type == 'gene/protein') & \n", + " (primekg_edges.tail_index.isin(ibd_protein_index))],\n", + " primekg_edges[(primekg_edges.tail_type == 'pathway') & \n", + " (primekg_edges.head_type == 'gene/protein') & \n", + " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", + "\n", + "# Check dataframe\n", + "ibd_pathway_protein_edges_df" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "array([ 62341, 62347, 62348, 62373, 62376, 62394, 62400, 62401,\n", + " 62404, 62405, 62414, 62448, 62449, 62462, 62465, 62467,\n", + " 62469, 62472, 62476, 62477, 62483, 62543, 62571, 62573,\n", + " 62575, 62583, 62588, 62596, 62603, 62606, 62628, 62644,\n", + " 62651, 62655, 62657, 62672, 62675, 62691, 62692, 62697,\n", + " 62702, 62703, 62711, 62717, 62733, 62734, 62768, 62770,\n", + " 62805, 62807, 62836, 62865, 62916, 62925, 62931, 62968,\n", + " 62976, 62987, 62996, 63041, 63064, 63071, 63076, 127601,\n", + " 127615, 127616, 127617, 127619, 127620, 127624, 127628, 127629,\n", + " 127639, 127640, 127649, 127659, 127662, 127682, 127683, 127688,\n", + " 127691, 127693, 127694, 127695, 127696, 127726, 127727, 127728,\n", + " 127729, 127730, 127731, 127732, 127733, 127791, 127797, 127810,\n", + " 127814, 127815, 127833, 127835, 127856, 127858, 127866, 127867,\n", + " 127869, 127886, 127891, 127908, 127917, 127918, 127921, 127928,\n", + " 127958, 127960, 127971, 127977, 127999, 128001, 128002, 128003,\n", + " 128008, 128010, 128015, 128018, 128022, 128025, 128034, 128058,\n", + " 128065, 128071, 128072, 128073, 128074, 128078, 128079, 128080,\n", + " 128086, 128111, 128113, 128116, 128117, 128129, 128137, 128138,\n", + " 128139, 128158, 128165, 128170, 128176, 128183, 128186, 128191,\n", + " 128198, 128199, 128204, 128208, 128209, 128224, 128227, 128242,\n", + " 128243, 128244, 128253, 128254, 128270, 128271, 128272, 128273,\n", + " 128299, 128302, 128341, 128348, 128349, 128350, 128351, 128353,\n", + " 128360, 128378, 128381, 128393, 128395, 128396, 128399, 128430,\n", + " 128440, 128453, 128460, 128470, 128472, 128473, 128477, 128478,\n", + " 128479, 128480, 128481, 128482, 128483, 128484, 128486, 128487,\n", + " 128497, 128498, 128499, 128500, 128501, 128503, 128527, 128535,\n", + " 128550, 128593, 128599, 128601, 128602, 128604, 128655, 128677,\n", + " 128715, 128759, 128766, 128767, 128779, 128781, 128782, 128783,\n", + " 128784, 128789, 128792, 128801, 128804, 128814, 128815, 128827,\n", + " 128828, 128829, 128830, 128832, 128835, 128837, 128838, 128841,\n", + " 128846, 128851, 128852, 128878, 128976, 128977, 128978, 128979,\n", + " 128980, 128981, 128988, 128990, 129007, 129015, 129016, 129021,\n", + " 129023, 129035, 129039, 129040, 129042, 129044, 129047, 129048,\n", + " 129052, 129099, 129110, 129124, 129125, 129126, 129127, 129128,\n", + " 129131, 129135, 129136, 129139, 129140, 129141, 129148, 129155,\n", + " 129167, 129181, 129183, 129190, 129195, 129196, 129197, 129198,\n", + " 129215, 129217, 129238, 129257, 129258, 129259, 129264, 129266,\n", + " 129289, 129294, 129296, 129302, 129303, 129310, 129355, 129360,\n", + " 129361, 129365, 129366, 129367])" + ] + }, + "execution_count": 10, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Get unique protein index\n", + "ibd_pathway_index = np.unique(np.concatenate([ibd_pathway_protein_edges_df[ibd_pathway_protein_edges_df.head_type == 'pathway'].head_index.unique(),\n", + " ibd_pathway_protein_edges_df[ibd_pathway_protein_edges_df.tail_type == 'pathway'].tail_index.unique()]))\n", + "ibd_pathway_index" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Pathway-Pathway Relationship" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "As well as, a set of records containing the relationships of pathway-pathway nodes." + ] + }, + { + "cell_type": "code", + "execution_count": 11, + "metadata": {}, + "outputs": [], + "source": [ + "# # # IBD pathway_pathway edges \n", + "# ibd_pathway_pathway_edges_df = pd.concat([primekg_edges[(primekg_edges.head_index.isin(ibd_pathway_index)) & \n", + "# (primekg_edges.tail_type == 'pathway')],\n", + "# primekg_edges[(primekg_edges.tail_index.isin(ibd_pathway_index)) & \n", + "# (primekg_edges.head_type == 'pathway')]])\n", + "\n", + "# # Check dataframe\n", + "# ibd_pathway_pathway_edges_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Bioprocess-Protein Relationship" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Next step is to get the records containing the relationships of biological_process-gene/protein nodes." + ] + }, + { + "cell_type": "code", + "execution_count": 12, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
6351294112487neutrophil degranulationGO43312biological_process1990FCGR2ANCBI2212gene/proteininteracts withbioprocess_protein
6351300112487neutrophil degranulationGO43312biological_process3333FPR2NCBI2358gene/proteininteracts withbioprocess_protein
6351340112487neutrophil degranulationGO43312biological_process2012CXCR1NCBI3577gene/proteininteracts withbioprocess_protein
6351341112487neutrophil degranulationGO43312biological_process3064CXCR2NCBI3579gene/proteininteracts withbioprocess_protein
6351346112487neutrophil degranulationGO43312biological_process5022ITGAMNCBI3684gene/proteininteracts withbioprocess_protein
.......................................
37817072111LRRK2NCBI120892gene/protein51599negative regulation of peroxidase activityGO2000469biological_processinteracts withbioprocess_protein
37817082111LRRK2NCBI120892gene/protein52358regulation of kidney sizeGO35564biological_processinteracts withbioprocess_protein
37817102111LRRK2NCBI120892gene/protein109343negative regulation of thioredoxin peroxidase ...GO1903125biological_processinteracts withbioprocess_protein
378181122105GPBAR1NCBI151306gene/protein105254cell surface bile acid receptor signaling pathwayGO38184biological_processinteracts withbioprocess_protein
378182434779NKX2-3NCBI159296gene/protein100699post-embryonic digestive tract morphogenesisGO48621biological_processinteracts withbioprocess_protein
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6300 rows × 12 columns

\n", + "
" + ], + "text/plain": [ + " head_index head_name head_source head_id \\\n", + "6351294 112487 neutrophil degranulation GO 43312 \n", + "6351300 112487 neutrophil degranulation GO 43312 \n", + "6351340 112487 neutrophil degranulation GO 43312 \n", + "6351341 112487 neutrophil degranulation GO 43312 \n", + "6351346 112487 neutrophil degranulation GO 43312 \n", + "... ... ... ... ... \n", + "3781707 2111 LRRK2 NCBI 120892 \n", + "3781708 2111 LRRK2 NCBI 120892 \n", + "3781710 2111 LRRK2 NCBI 120892 \n", + "3781811 22105 GPBAR1 NCBI 151306 \n", + "3781824 34779 NKX2-3 NCBI 159296 \n", + "\n", + " head_type tail_index \\\n", + "6351294 biological_process 1990 \n", + "6351300 biological_process 3333 \n", + "6351340 biological_process 2012 \n", + "6351341 biological_process 3064 \n", + "6351346 biological_process 5022 \n", + "... ... ... \n", + "3781707 gene/protein 51599 \n", + "3781708 gene/protein 52358 \n", + "3781710 gene/protein 109343 \n", + "3781811 gene/protein 105254 \n", + "3781824 gene/protein 100699 \n", + "\n", + " tail_name tail_source \\\n", + "6351294 FCGR2A NCBI \n", + "6351300 FPR2 NCBI \n", + "6351340 CXCR1 NCBI \n", + "6351341 CXCR2 NCBI \n", + "6351346 ITGAM NCBI \n", + "... ... ... \n", + "3781707 negative regulation of peroxidase activity GO \n", + "3781708 regulation of kidney size GO \n", + "3781710 negative regulation of thioredoxin peroxidase ... GO \n", + "3781811 cell surface bile acid receptor signaling pathway GO \n", + "3781824 post-embryonic digestive tract morphogenesis GO \n", + "\n", + " tail_id tail_type display_relation relation \n", + "6351294 2212 gene/protein interacts with bioprocess_protein \n", + "6351300 2358 gene/protein interacts with bioprocess_protein \n", + "6351340 3577 gene/protein interacts with bioprocess_protein \n", + "6351341 3579 gene/protein interacts with bioprocess_protein \n", + "6351346 3684 gene/protein interacts with bioprocess_protein \n", + "... ... ... ... ... \n", + "3781707 2000469 biological_process interacts with bioprocess_protein \n", + "3781708 35564 biological_process interacts with bioprocess_protein \n", + "3781710 1903125 biological_process interacts with bioprocess_protein \n", + "3781811 38184 biological_process interacts with bioprocess_protein \n", + "3781824 48621 biological_process interacts with bioprocess_protein \n", + "\n", + "[6300 rows x 12 columns]" + ] + }, + "execution_count": 12, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# IBD bioprocess_protein edges \n", + "ibd_bioprocess_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'biological_process') & \n", + " (primekg_edges.tail_type == 'gene/protein') & \n", + " (primekg_edges.tail_index.isin(ibd_protein_index))],\n", + " primekg_edges[(primekg_edges.tail_type == 'biological_process') & \n", + " (primekg_edges.head_type == 'gene/protein') & \n", + " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", + "\n", + "# Check dataframe\n", + "ibd_bioprocess_protein_edges_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### MolFunc-Protein Relationship" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Here, we would like to get biological_process-gene/protein relationships." + ] + }, + { + "cell_type": "code", + "execution_count": 13, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
619826454035interleukin-1 bindingGO19966molecular_function1654IL1R2NCBI7850gene/proteininteracts withmolfunc_protein
619835954290enzyme bindingGO19899molecular_function3578ECM1NCBI1893gene/proteininteracts withmolfunc_protein
619836654290enzyme bindingGO19899molecular_function2057FN1NCBI2335gene/proteininteracts withmolfunc_protein
619844254290enzyme bindingGO19899molecular_function989PPARGNCBI5468gene/proteininteracts withmolfunc_protein
619846254290enzyme bindingGO19899molecular_function772RELANCBI5970gene/proteininteracts withmolfunc_protein
.......................................
35535336229NOD2NCBI64127gene/protein122117muramyl dipeptide bindingGO32500molecular_functioninteracts withmolfunc_protein
35537702111LRRK2NCBI120892gene/protein115199GTP-dependent protein kinase activityGO34211molecular_functioninteracts withmolfunc_protein
35537712111LRRK2NCBI120892gene/protein118105beta-catenin destruction complex bindingGO1904713molecular_functioninteracts withmolfunc_protein
35537732111LRRK2NCBI120892gene/protein119847peroxidase inhibitor activityGO36479molecular_functioninteracts withmolfunc_protein
355383222105GPBAR1NCBI151306gene/protein116806G protein-coupled bile acid receptor activityGO38182molecular_functioninteracts withmolfunc_protein
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1466 rows × 12 columns

\n", + "
" + ], + "text/plain": [ + " head_index head_name head_source head_id \\\n", + "6198264 54035 interleukin-1 binding GO 19966 \n", + "6198359 54290 enzyme binding GO 19899 \n", + "6198366 54290 enzyme binding GO 19899 \n", + "6198442 54290 enzyme binding GO 19899 \n", + "6198462 54290 enzyme binding GO 19899 \n", + "... ... ... ... ... \n", + "3553533 6229 NOD2 NCBI 64127 \n", + "3553770 2111 LRRK2 NCBI 120892 \n", + "3553771 2111 LRRK2 NCBI 120892 \n", + "3553773 2111 LRRK2 NCBI 120892 \n", + "3553832 22105 GPBAR1 NCBI 151306 \n", + "\n", + " head_type tail_index \\\n", + "6198264 molecular_function 1654 \n", + "6198359 molecular_function 3578 \n", + "6198366 molecular_function 2057 \n", + "6198442 molecular_function 989 \n", + "6198462 molecular_function 772 \n", + "... ... ... \n", + "3553533 gene/protein 122117 \n", + "3553770 gene/protein 115199 \n", + "3553771 gene/protein 118105 \n", + "3553773 gene/protein 119847 \n", + "3553832 gene/protein 116806 \n", + "\n", + " tail_name tail_source tail_id \\\n", + "6198264 IL1R2 NCBI 7850 \n", + "6198359 ECM1 NCBI 1893 \n", + "6198366 FN1 NCBI 2335 \n", + "6198442 PPARG NCBI 5468 \n", + "6198462 RELA NCBI 5970 \n", + "... ... ... ... \n", + "3553533 muramyl dipeptide binding GO 32500 \n", + "3553770 GTP-dependent protein kinase activity GO 34211 \n", + "3553771 beta-catenin destruction complex binding GO 1904713 \n", + "3553773 peroxidase inhibitor activity GO 36479 \n", + "3553832 G protein-coupled bile acid receptor activity GO 38182 \n", + "\n", + " tail_type display_relation relation \n", + "6198264 gene/protein interacts with molfunc_protein \n", + "6198359 gene/protein interacts with molfunc_protein \n", + "6198366 gene/protein interacts with molfunc_protein \n", + "6198442 gene/protein interacts with molfunc_protein \n", + "6198462 gene/protein interacts with molfunc_protein \n", + "... ... ... ... \n", + "3553533 molecular_function interacts with molfunc_protein \n", + "3553770 molecular_function interacts with molfunc_protein \n", + "3553771 molecular_function interacts with molfunc_protein \n", + "3553773 molecular_function interacts with molfunc_protein \n", + "3553832 molecular_function interacts with molfunc_protein \n", + "\n", + "[1466 rows x 12 columns]" + ] + }, + "execution_count": 13, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# IBD molfunc_protein edges \n", + "ibd_molfunc_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'molecular_function') & \n", + " (primekg_edges.tail_type == 'gene/protein') & \n", + " (primekg_edges.tail_index.isin(ibd_protein_index))],\n", + " primekg_edges[(primekg_edges.tail_type == 'molecular_function') & \n", + " (primekg_edges.head_type == 'gene/protein') & \n", + " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", + "\n", + "# Check dataframe\n", + "ibd_molfunc_protein_edges_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### CellComp-Protein Relationship" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Finally, we are getting the records containing the relationships of cellular_component-gene/protein nodes." + ] + }, + { + "cell_type": "code", + "execution_count": 14, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
6267848126078ficolin-1-rich granule lumenGO1904813cellular_component3474MMP9NCBI4318gene/proteininteracts withcellcomp_protein
6268120124245extracellular spaceGO5615cellular_component2384CRPNCBI1401gene/proteininteracts withcellcomp_protein
6268163124245extracellular spaceGO5615cellular_component5805DEFA5NCBI1670gene/proteininteracts withcellcomp_protein
6268164124245extracellular spaceGO5615cellular_component657DEFA6NCBI1671gene/proteininteracts withcellcomp_protein
6268173124245extracellular spaceGO5615cellular_component3578ECM1NCBI1893gene/proteininteracts withcellcomp_protein
.......................................
36367082139ARPC2NCBI10109gene/protein126261muscle cell projection membraneGO36195cellular_componentinteracts withcellcomp_protein
36368199763ORMDL3NCBI94103gene/protein126815SPOTS complexGO35339cellular_componentinteracts withcellcomp_protein
36372116661ATG16L1NCBI55054gene/protein126444vacuole-isolation membrane contact siteGO120095cellular_componentinteracts withcellcomp_protein
36372342111LRRK2NCBI120892gene/protein126938cytoplasmic side of mitochondrial outer membraneGO32473cellular_componentinteracts withcellcomp_protein
36373282111LRRK2NCBI120892gene/protein125942caveola neckGO99400cellular_componentinteracts withcellcomp_protein
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1348 rows × 12 columns

\n", + "
" + ], + "text/plain": [ + " head_index head_name head_source head_id \\\n", + "6267848 126078 ficolin-1-rich granule lumen GO 1904813 \n", + "6268120 124245 extracellular space GO 5615 \n", + "6268163 124245 extracellular space GO 5615 \n", + "6268164 124245 extracellular space GO 5615 \n", + "6268173 124245 extracellular space GO 5615 \n", + "... ... ... ... ... \n", + "3636708 2139 ARPC2 NCBI 10109 \n", + "3636819 9763 ORMDL3 NCBI 94103 \n", + "3637211 6661 ATG16L1 NCBI 55054 \n", + "3637234 2111 LRRK2 NCBI 120892 \n", + "3637328 2111 LRRK2 NCBI 120892 \n", + "\n", + " head_type tail_index \\\n", + "6267848 cellular_component 3474 \n", + "6268120 cellular_component 2384 \n", + "6268163 cellular_component 5805 \n", + "6268164 cellular_component 657 \n", + "6268173 cellular_component 3578 \n", + "... ... ... \n", + "3636708 gene/protein 126261 \n", + "3636819 gene/protein 126815 \n", + "3637211 gene/protein 126444 \n", + "3637234 gene/protein 126938 \n", + "3637328 gene/protein 125942 \n", + "\n", + " tail_name tail_source tail_id \\\n", + "6267848 MMP9 NCBI 4318 \n", + "6268120 CRP NCBI 1401 \n", + "6268163 DEFA5 NCBI 1670 \n", + "6268164 DEFA6 NCBI 1671 \n", + "6268173 ECM1 NCBI 1893 \n", + "... ... ... ... \n", + "3636708 muscle cell projection membrane GO 36195 \n", + "3636819 SPOTS complex GO 35339 \n", + "3637211 vacuole-isolation membrane contact site GO 120095 \n", + "3637234 cytoplasmic side of mitochondrial outer membrane GO 32473 \n", + "3637328 caveola neck GO 99400 \n", + "\n", + " tail_type display_relation relation \n", + "6267848 gene/protein interacts with cellcomp_protein \n", + "6268120 gene/protein interacts with cellcomp_protein \n", + "6268163 gene/protein interacts with cellcomp_protein \n", + "6268164 gene/protein interacts with cellcomp_protein \n", + "6268173 gene/protein interacts with cellcomp_protein \n", + "... ... ... ... \n", + "3636708 cellular_component interacts with cellcomp_protein \n", + "3636819 cellular_component interacts with cellcomp_protein \n", + "3637211 cellular_component interacts with cellcomp_protein \n", + "3637234 cellular_component interacts with cellcomp_protein \n", + "3637328 cellular_component interacts with cellcomp_protein \n", + "\n", + "[1348 rows x 12 columns]" + ] + }, + "execution_count": 14, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# IBD molfunc_protein edges \n", + "ibd_cellcomp_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'cellular_component') & \n", + " (primekg_edges.tail_type == 'gene/protein') & \n", + " (primekg_edges.tail_index.isin(ibd_protein_index))],\n", + " primekg_edges[(primekg_edges.tail_type == 'cellular_component') & \n", + " (primekg_edges.head_type == 'gene/protein') & \n", + " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", + "\n", + "# Check dataframe\n", + "ibd_cellcomp_protein_edges_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Merge all dataframes" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Once we have all of particular type of edges, we can merge them into a single dataframe representing a subgraph of IBD inferred from PrimeKG." + ] + }, + { + "cell_type": "code", + "execution_count": 15, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelationedge_type
037785ulcerative colitis (disease)MONDO5101disease7359ADCY7NCBI113gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
128158inflammatory bowel diseaseMONDO_grouped9960_12845_33643_11471_12831_12875_12941_13153...disease7359ADCY7NCBI113gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
237785ulcerative colitis (disease)MONDO5101disease2874PRDM1NCBI639gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
328158inflammatory bowel diseaseMONDO_grouped9960_12845_33643_11471_12831_12875_12941_13153...disease2874PRDM1NCBI639gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
437785ulcerative colitis (disease)MONDO5101disease2712CASP3NCBI836gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
..........................................
127472139ARPC2NCBI10109gene/protein126261muscle cell projection membraneGO36195cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
127489763ORMDL3NCBI94103gene/protein126815SPOTS complexGO35339cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
127496661ATG16L1NCBI55054gene/protein126444vacuole-isolation membrane contact siteGO120095cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
127502111LRRK2NCBI120892gene/protein126938cytoplasmic side of mitochondrial outer membraneGO32473cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
127512111LRRK2NCBI120892gene/protein125942caveola neckGO99400cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
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12752 rows × 13 columns

\n", + "
" + ], + "text/plain": [ + " head_index head_name head_source \\\n", + "0 37785 ulcerative colitis (disease) MONDO \n", + "1 28158 inflammatory bowel disease MONDO_grouped \n", + "2 37785 ulcerative colitis (disease) MONDO \n", + "3 28158 inflammatory bowel disease MONDO_grouped \n", + "4 37785 ulcerative colitis (disease) MONDO \n", + "... ... ... ... \n", + "12747 2139 ARPC2 NCBI \n", + "12748 9763 ORMDL3 NCBI \n", + "12749 6661 ATG16L1 NCBI \n", + "12750 2111 LRRK2 NCBI \n", + "12751 2111 LRRK2 NCBI \n", + "\n", + " head_id head_type \\\n", + "0 5101 disease \n", + "1 9960_12845_33643_11471_12831_12875_12941_13153... disease \n", + "2 5101 disease \n", + "3 9960_12845_33643_11471_12831_12875_12941_13153... disease \n", + "4 5101 disease \n", + "... ... ... \n", + "12747 10109 gene/protein \n", + "12748 94103 gene/protein \n", + "12749 55054 gene/protein \n", + "12750 120892 gene/protein \n", + "12751 120892 gene/protein \n", + "\n", + " tail_index tail_name \\\n", + "0 7359 ADCY7 \n", + "1 7359 ADCY7 \n", + "2 2874 PRDM1 \n", + "3 2874 PRDM1 \n", + "4 2712 CASP3 \n", + "... ... ... \n", + "12747 126261 muscle cell projection membrane \n", + "12748 126815 SPOTS complex \n", + "12749 126444 vacuole-isolation membrane contact site \n", + "12750 126938 cytoplasmic side of mitochondrial outer membrane \n", + "12751 125942 caveola neck \n", + "\n", + " tail_source tail_id tail_type display_relation \\\n", + "0 NCBI 113 gene/protein associated with \n", + "1 NCBI 113 gene/protein associated with \n", + "2 NCBI 639 gene/protein associated with \n", + "3 NCBI 639 gene/protein associated with \n", + "4 NCBI 836 gene/protein associated with \n", + "... ... ... ... ... \n", + "12747 GO 36195 cellular_component interacts with \n", + "12748 GO 35339 cellular_component interacts with \n", + "12749 GO 120095 cellular_component interacts with \n", + "12750 GO 32473 cellular_component interacts with \n", + "12751 GO 99400 cellular_component interacts with \n", + "\n", + " relation edge_type \n", + "0 disease_protein (disease, associated with, gene/protein) \n", + "1 disease_protein (disease, associated with, gene/protein) \n", + "2 disease_protein (disease, associated with, gene/protein) \n", + "3 disease_protein (disease, associated with, gene/protein) \n", + "4 disease_protein (disease, associated with, gene/protein) \n", + "... ... ... \n", + "12747 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + "12748 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + "12749 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + "12750 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + "12751 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + "\n", + "[12752 rows x 13 columns]" + ] + }, + "execution_count": 15, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# PrimeKG edges related to IBD\n", + "primekg_ibd_edges_df = pd.concat([ibd_disease_protein_edges_df,\n", + " # ibd_disease_disease_edges_df,\n", + " # ibd_protein_protein_edges_df,\n", + " ibd_drug_protein_edges_df,\n", + " ibd_pathway_protein_edges_df,\n", + " # ibd_pathway_pathway_edges_df,\n", + " ibd_bioprocess_protein_edges_df,\n", + " ibd_molfunc_protein_edges_df,\n", + " ibd_cellcomp_protein_edges_df])\n", + "primekg_ibd_edges_df[\"edge_type\"] = primekg_ibd_edges_df.apply(lambda x: (x.head_type, x.display_relation, x.tail_type), axis=1)\n", + "primekg_ibd_edges_df.drop_duplicates(subset=['head_index', 'tail_index'], inplace=True)\n", + "primekg_ibd_edges_df.reset_index(drop=True, inplace=True)\n", + "primekg_ibd_edges_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "We can get a dataframe of nodes based on the above edge dataframe as follows:" + ] + }, + { + "cell_type": "code", + "execution_count": 16, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
\n", + "\n", + "\n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + " \n", + "
node_indexnode_namenode_sourcenode_idnode_type
144144SMAD3NCBI4088gene/protein
179179IL10RBNCBI3588gene/protein
192192GNA12NCBI2768gene/protein
279279HNF4ANCBI3172gene/protein
417417VCAM1NCBI7412gene/protein
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129360129360IRAK2 mediated activation of TAK1 complex upon...REACTOMER-HSA-975163pathway
129361129361TRAF6 mediated IRF7 activation in TLR7/8 or 9 ...REACTOMER-HSA-975110pathway
129365129365Antigen processing: Ubiquitination & Proteasom...REACTOMER-HSA-983168pathway
129366129366Antigen Presentation: Folding, assembly and pe...REACTOMER-HSA-983170pathway
129367129367KinesinsREACTOMER-HSA-983189pathway
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3426 rows × 5 columns

\n", + "
" + ], + "text/plain": [ + " node_index node_name \\\n", + "144 144 SMAD3 \n", + "179 179 IL10RB \n", + "192 192 GNA12 \n", + "279 279 HNF4A \n", + "417 417 VCAM1 \n", + "... ... ... \n", + "129360 129360 IRAK2 mediated activation of TAK1 complex upon... \n", + "129361 129361 TRAF6 mediated IRF7 activation in TLR7/8 or 9 ... \n", + "129365 129365 Antigen processing: Ubiquitination & Proteasom... \n", + "129366 129366 Antigen Presentation: Folding, assembly and pe... \n", + "129367 129367 Kinesins \n", + "\n", + " node_source node_id node_type \n", + "144 NCBI 4088 gene/protein \n", + "179 NCBI 3588 gene/protein \n", + "192 NCBI 2768 gene/protein \n", + "279 NCBI 3172 gene/protein \n", + "417 NCBI 7412 gene/protein \n", + "... ... ... ... \n", + "129360 REACTOME R-HSA-975163 pathway \n", + "129361 REACTOME R-HSA-975110 pathway \n", + "129365 REACTOME R-HSA-983168 pathway \n", + "129366 REACTOME R-HSA-983170 pathway \n", + "129367 REACTOME R-HSA-983189 pathway \n", + "\n", + "[3426 rows x 5 columns]" + ] + }, + "execution_count": 16, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# PrimeKG nodes related to IBD\n", + "primekg_ibd_nodes_df = primekg_nodes[primekg_nodes.index.isin(np.unique(np.hstack([primekg_ibd_edges_df.head_index.unique(), \n", + " primekg_ibd_edges_df.tail_index.unique()])))]\n", + "primekg_ibd_nodes_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "We can store the nodes and edges related to IBD in a parquet file for future use." + ] + }, + { + "cell_type": "code", + "execution_count": 17, + "metadata": {}, + "outputs": [], + "source": [ + "# Store the IBD-related nodes and edges\n", + "local_dir = '../../../../data/primekg_ibd/'\n", + "if not os.path.exists(local_dir):\n", + " os.makedirs(local_dir)\n", + "primekg_ibd_nodes_df.to_parquet(os.path.join(local_dir, 'primekg_ibd_nodes.parquet'), compression='gzip', index=False)\n", + "primekg_ibd_edges_df.to_parquet(os.path.join(local_dir, 'primekg_ibd_edges.parquet'), compression='gzip', index=False)" + ] + }, + { + "cell_type": "code", + "execution_count": 18, + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Number of IBD-related nodes: 3426\n", + "Number of IBD-related edges: 12752\n" + ] + } + ], + "source": [ + "# Statistics over the IBD-related nodes and edges\n", + "print(f\"Number of IBD-related nodes: {primekg_ibd_nodes_df.shape[0]}\")\n", + "print(f\"Number of IBD-related edges: {primekg_ibd_edges_df.shape[0]}\")" + ] + }, + { + "cell_type": "code", + "execution_count": 19, + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "node_type\n", + "biological_process 1642\n", + "cellular_component 207\n", + "disease 7\n", + "drug 835\n", + "gene/protein 103\n", + "molecular_function 324\n", + "pathway 308\n", + "dtype: int64" + ] + }, + "execution_count": 19, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Count the number of nodes by node type\n", + "primekg_ibd_nodes_df.groupby('node_type').size()" + ] + }, + { + "cell_type": "code", + "execution_count": 20, + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "relation display_relation\n", + "bioprocess_protein interacts with 6300\n", + "cellcomp_protein interacts with 1348\n", + "disease_protein associated with 620\n", + "drug_protein carrier 8\n", + " enzyme 64\n", + " target 776\n", + " transporter 1140\n", + "molfunc_protein interacts with 1466\n", + "pathway_protein interacts with 1030\n", + "dtype: int64" + ] + }, + "execution_count": 20, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Count the number of edges by relation and display_relation\n", + "primekg_ibd_edges_df.groupby(['relation','display_relation']).size()" + ] + }, + { + "cell_type": "code", + "execution_count": 21, + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "edge_type\n", + "(biological_process, interacts with, gene/protein) 3150\n", + "(cellular_component, interacts with, gene/protein) 674\n", + "(disease, associated with, gene/protein) 310\n", + "(drug, carrier, gene/protein) 4\n", + "(drug, enzyme, gene/protein) 32\n", + "(drug, target, gene/protein) 388\n", + "(drug, transporter, gene/protein) 570\n", + "(gene/protein, associated with, disease) 310\n", + "(gene/protein, carrier, drug) 4\n", + "(gene/protein, enzyme, drug) 32\n", + "(gene/protein, interacts with, biological_process) 3150\n", + "(gene/protein, interacts with, cellular_component) 674\n", + "(gene/protein, interacts with, molecular_function) 733\n", + "(gene/protein, interacts with, pathway) 515\n", + "(gene/protein, target, drug) 388\n", + "(gene/protein, transporter, drug) 570\n", + "(molecular_function, interacts with, gene/protein) 733\n", + "(pathway, interacts with, gene/protein) 515\n", + "dtype: int64" + ] + }, + "execution_count": 21, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Count the number of edges by edge type\n", + "primekg_ibd_edges_df.groupby(['edge_type']).size()" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Enrichment (using textual as of now)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "From this point onwards, we will use the pre-processed IBD-related nodes and edges to create a set of graph formats.\n", + "\n", + "Before that, we should perform enrichment and embedding over the IBD-related nodes and edges.\n", + "\n", + "As of now, we will conduct a textual enrichment over the records.\n", + "\n", + "Since StarQA provide most of information of the nodes, we will use StarkQA to get the information of the nodes related to IBD." + ] + }, + { + "cell_type": "code", + "execution_count": 33, + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Loading StarkQAPrimeKG dataset...\n", + "../../../../data/starkqa_primekg/qa/prime/stark_qa/stark_qa.csv already exists. Loading the data from the local directory.\n", + "Loading StarkQAPrimeKG embeddings...\n" + ] + } + ], + "source": [ + "# Define starkqa primekg data by providing a local directory where the data is stored\n", + "starkqa_data = StarkQAPrimeKG(local_dir=\"../../../../data/starkqa_primekg/\")\n", + "\n", + "# Invoke a method to load the data\n", + "starkqa_data.load_data()\n", + "\n", + "# Get the StarkQAPrimeKG data, which are the QA pairs, split indices, and the node information\n", + "# starkqa_df = starkqa_data.get_starkqa()\n", + "starkqa_node_info = starkqa_data.get_starkqa_node_info()" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Note that not all nodes in the StarkQA-PrimeKG have additional information. \n", + "\n", + "For this case, we provide a basic text enrichment for the nodes by simply specifying their node name and type." + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "def do_enrichment_text(data, starkqa_node_info):\n", + " \"\"\"\n", + " Enrich the node with additional textual information from BioBridge and StarkQA.\n", + "\n", + " Args:\n", + " data (dict): The node data from PrimeKG\n", + " starkqa_node_info (dict): The node information from StarkQA-PrimeKG\n", + " \"\"\"\n", + " # Basic textual enrichment of the node\n", + " enriched_node = f\"{data['node_name']} belongs to {data['node_type']} category. \"\n", + "\n", + " # Only enrich the node if the node type is gene/protein, drug, disease, or pathway, which\n", + " # has additional information in the node_info of StarkQA-PrimeKG\n", + " added_info = ''\n", + " if data['node_type'] == 'gene/protein':\n", + " added_info = starkqa_node_info['details']['summary'] if 'summary' in starkqa_node_info['details'] else ''\n", + " elif data['node_type'] == 'drug':\n", + " added_info = ' '.join([str(starkqa_node_info['details']['description']).replace('nan', ''),\n", + " str(starkqa_node_info['details']['mechanism_of_action']).replace('nan', ''),\n", + " str(starkqa_node_info['details']['protein_binding']).replace('nan', ''),\n", + " str(starkqa_node_info['details']['pharmacodynamics']).replace('nan', ''),\n", + " str(starkqa_node_info['details']['indication']).replace('nan', '')])\n", + " elif data['node_type'] == 'disease':\n", + " added_info = ' '.join([str(starkqa_node_info['details']['mondo_definition']).replace('nan', ''),\n", + " str(starkqa_node_info['details']['mayo_symptoms']).replace('nan', ''),\n", + " str(starkqa_node_info['details']['mayo_causes']).replace('nan', '')])\n", + " elif data['node_type'] == 'pathway':\n", + " added_info += f\"This pathway found in {starkqa_node_info['details']['speciesName']}. \" + ' '.join([x['text'] for x in starkqa_node_info['details']['summation']]) if 'details' in starkqa_node_info else ''\n", + "\n", + " # Append the additional information for enrichment\n", + " enriched_node += added_info\n", + " return enriched_node" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "By using the above function, we can enrich the node information from PrimeKG with additional information from StarkQA-PrimeKG as shown below:" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Perform node enrichment for each row in primekg_nodes\n", + "text_enriched_nodes = primekg_ibd_nodes_df.apply(lambda x: do_enrichment_text(x, starkqa_node_info[x['node_index']]), axis=1).tolist()\n", + "primekg_ibd_nodes_df['enriched_node'] = text_enriched_nodes\n", + "primekg_ibd_nodes_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Subsequently, we can perform similar textual enrichment for the edges in PrimeKG.\n", + "\n", + "Since StarkQA only provides node information, we can only enrich the edges with basic information of the triples in combination with the head and tail nodes." + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Perform textual enrichment over the edges by simply concatenating the head and tail nodes with the relation followed by the enriched node information\n", + "text_enriched_edges = primekg_ibd_edges_df.apply(lambda x: f\"{x['head_name']} ({x['head_type']}) has a direct relationship of {x['relation']}:{x['display_relation']} with {x['tail_name']} ({x['tail_type']}).\", axis=1).tolist()\n", + "primekg_ibd_edges_df['enriched_edge'] = text_enriched_edges\n", + "primekg_ibd_edges_df.head()" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Embeddings (using textual embedding as of now)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "We are going to perform embedding using the enriched nodes and edges by leveraging `EmbeddingWithOllama` class.\n", + "\n", + "For this purpose, we will use `nomic-embed-text`." + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Using nomic-ai/nomic-embed-text-v1.5 model\n", + "emb_model = EmbeddingWithOllama(model_name='nomic-embed-text')" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Node Embedding" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "We will perform node embedding for the IBD-related nodes using the Ollama model by using mini-batches of 100 nodes at a time." + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Since the records of nodes has large amount of data, we will split them into mini-batches\n", + "mini_batch_size = 100\n", + "node_embeddings = []\n", + "for i in tqdm(range(0, primekg_ibd_nodes_df.shape[0], mini_batch_size)):\n", + " outputs = emb_model.embed_documents(primekg_ibd_nodes_df.enriched_node.values.tolist()[i:i+mini_batch_size])\n", + " node_embeddings.extend(outputs)\n", + "# node_embeddings" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Check the shape of the node embeddings\n", + "len(node_embeddings), len(node_embeddings[0])" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Add them as features to the dataframe\n", + "primekg_ibd_nodes_df['x'] = node_embeddings\n", + "\n", + "# Drop and rename several columns\n", + "primekg_ibd_nodes_df.drop(columns=['node_source', 'node_id'], inplace=True)\n", + "primekg_ibd_nodes_df.rename(columns={'node_index': 'node_id'}, inplace=True)\n", + "\n", + "# Check dataframe of nodes\n", + "primekg_ibd_nodes_df.head()" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Duplicate a node_name as index and use it as index\n", + "primekg_ibd_nodes_df['node'] = primekg_ibd_nodes_df['node_id']\n", + "primekg_ibd_nodes_df.set_index('node', inplace=True)\n", + "primekg_ibd_nodes_df.head()" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Save the embedded nodes dataframes to parquet file\n", + "primekg_ibd_nodes_df.to_parquet(os.path.join(local_dir, 'primekg_ibd_nodes_embedded.parquet'), compression='gzip', index=False)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "#### Edge Embedding" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Likewise, we also conduct node embedding for the IBD-related edges using the Ollama model by using mini-batches of 100 edges at a time." + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Since the records of edges has large amount of data, we will split them into mini-batches\n", + "mini_batch_size = 100\n", + "edge_embeddings = []\n", + "for i in tqdm(range(0, primekg_ibd_edges_df.shape[0], mini_batch_size)):\n", + " outputs = emb_model.embed_documents(primekg_ibd_edges_df.enriched_edge.values.tolist()[i:i+mini_batch_size])\n", + " edge_embeddings.extend(outputs)\n", + "# edge_embeddings" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Check the shape of the edge embeddings\n", + "len(edge_embeddings), len(edge_embeddings[0])" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Add them as features to the dataframe\n", + "primekg_ibd_edges_df['edge_attr'] = edge_embeddings\n", + "\n", + "# Drop and rename several columns\n", + "primekg_ibd_edges_df.drop(columns=['head_source', 'head_id', 'head_type', 'tail_source', 'tail_id', 'tail_type', 'display_relation', 'relation'], inplace=True)\n", + "primekg_ibd_edges_df.rename(columns={'head_index': 'head_id', 'tail_index': 'tail_id'}, inplace=True)\n", + "\n", + "# Check dataframe of edges\n", + "primekg_ibd_edges_df.head()" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Save the embedded nodes dataframes to parquet file\n", + "primekg_ibd_edges_df.to_parquet(os.path.join(local_dir, 'primekg_ibd_edges_embedded.parquet'), compression='gzip', index=False)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Knowledge Graph Construction" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "For this section, we would like to convert our dataframes to networkx `DiGraph` object." + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Modify the node dataframe\n", + "primekg_ibd_nodes_df[\"node\"] = primekg_ibd_nodes_df.apply(lambda x: f\"{x.node_name}_({x.node_id})\", axis=1)\n", + "primekg_ibd_nodes_df[\"node_id\"] = primekg_ibd_nodes_df.apply(lambda x: f\"{x.node_name}_({x.node_id})\", axis=1)\n", + "primekg_ibd_nodes_df.set_index('node', inplace=True)\n", + "primekg_ibd_nodes_df.head()" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Modify the edge dataframe\n", + "primekg_ibd_edges_df[\"head_id\"] = primekg_ibd_edges_df.apply(lambda x: f\"{x.head_name}_({x.head_id})\", axis=1)\n", + "primekg_ibd_edges_df[\"tail_id\"] = primekg_ibd_edges_df.apply(lambda x: f\"{x.tail_name}_({x.tail_id})\", axis=1)\n", + "primekg_ibd_edges_df.reset_index(drop=True, inplace=True)\n", + "primekg_ibd_edges_df.head()" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# # Convert dataframes to knowledge graph as networkx object\n", + "kg = nx.DiGraph()\n", + "for i, row in primekg_ibd_nodes_df.iterrows():\n", + " kg.add_node(row['node_id'], **row.to_dict())\n", + "for i, row in primekg_ibd_edges_df.iterrows():\n", + " kg.add_edge(row['head_id'], row['tail_id'], key=i, **row.to_dict())\n" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Save graph object\n", + "local_dir = '../../../aiagents4pharma/talk2knowledgegraphs/tests/files/'\n", + "with open(os.path.join(local_dir, 'primekg_ibd_nx_graph.pkl'), 'wb') as f:\n", + " pickle.dump(kg, f)\n", + "\n", + "# # Load graph object\n", + "# with open(os.path.join(local_dir, 'primekg_ibd_nx_graph.pkl'), 'rb') as f:\n", + "# kg = pickle.load(f)\n" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "print (\"#Nodes\", kg.number_of_nodes())\n", + "print (\"#Edges\", kg.number_of_edges())" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "In addition, we can convert the networkx graph to PyG `Data` object for further processing (e.g., subgraph extraction)." + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Convert networkx graph to PyG data object\n", + "pyg_graph = from_networkx(kg)\n", + "\n", + "# Save graph object\n", + "with open(os.path.join(local_dir, 'primekg_ibd_pyg_graph.pkl'), 'wb') as f:\n", + " pickle.dump(pyg_graph, f)\n", + "\n", + "# Load graph object\n", + "# with open(os.path.join(local_dir, 'primekg_ibd_pyg_graph.pkl'), 'rb') as f:\n", + "# pyg_graph = pickle.load(f)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "Lastly, we are going to prepare a textualized graph of nodes and edges for RAG application, for instance.\n" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Prepare nodes\n", + "nodes_df = pd.DataFrame({\n", + " 'node_id': list(pyg_graph.node_id),\n", + " 'node_attr': list(pyg_graph.enriched_node),\n", + "})\n", + "nodes_df" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Prepare edges\n", + "edges_df = pd.DataFrame({\n", + " 'head_id': list(pyg_graph.head_id),\n", + " 'edge_type': list(pyg_graph.edge_type),\n", + " 'tail_id': list(pyg_graph.tail_id),\n", + "})\n", + "edges_df" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "with open(os.path.join(local_dir, 'primekg_ibd_text_graph.pkl'), \"wb\") as f:\n", + " pickle.dump({\"nodes\": nodes_df, \"edges\": edges_df}, f)" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [] + } + ], + "metadata": { + "kernelspec": { + "display_name": "Python (myenv)", + "language": "python", + "name": "myenv" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.11.11" + } + }, + "nbformat": 4, + "nbformat_minor": 4 +} From 7c4c28165e41d9310e31b3f40dd515b9b2d243d5 Mon Sep 17 00:00:00 2001 From: ShengZhaoDE Date: Fri, 7 Mar 2025 10:53:52 +0100 Subject: [PATCH 02/14] create a folder for notebook --- notebook/README.md | 0 1 file changed, 0 insertions(+), 0 deletions(-) create mode 100644 notebook/README.md diff --git a/notebook/README.md b/notebook/README.md new file mode 100644 index 00000000..e69de29b From 3fd4bee7b45771f4572a4be8783c6ee7ed9d55c1 Mon Sep 17 00:00:00 2001 From: ShengZhaoDE Date: Fri, 7 Mar 2025 12:17:56 +0100 Subject: [PATCH 03/14] add funciton for RAG on PDF file and sbml model --- notebook/data/Dwivedi_Model537_annotated.xml | 6736 ++++++++++++++++++ notebook/data/Dwivedi_Model537_empty.xml | 4628 ++++++++++++ notebook/data/Dwivedi_Model537_original.xml | 5522 ++++++++++++++ notebook/data/psp201364a.pdf | Bin 0 -> 695359 bytes notebook/pdf_keywords.txt | 1 + notebook/sbml_rag_notebook.ipynb | 287 + notebook/sbml_rag_utils.py | 288 + notebook/species_backgrounds.csv | 19 + 8 files changed, 17481 insertions(+) create mode 100644 notebook/data/Dwivedi_Model537_annotated.xml create mode 100644 notebook/data/Dwivedi_Model537_empty.xml create mode 100644 notebook/data/Dwivedi_Model537_original.xml create mode 100644 notebook/data/psp201364a.pdf create mode 100644 notebook/pdf_keywords.txt create mode 100644 notebook/sbml_rag_notebook.ipynb create mode 100644 notebook/sbml_rag_utils.py create mode 100644 notebook/species_backgrounds.csv diff --git a/notebook/data/Dwivedi_Model537_annotated.xml b/notebook/data/Dwivedi_Model537_annotated.xml new file mode 100644 index 00000000..6b9fd710 --- /dev/null +++ b/notebook/data/Dwivedi_Model537_annotated.xml @@ -0,0 +1,6736 @@ + + + + + + +
Dwivedi2014 - Crohns IL6 Disease model - +Anti-IL6R Antibody
+
This model is comprised of four models: +
+ Possible avenues for Interleukin-6 (IL-6) inhibition in +treating Crohn's disease are compared here. Each model refers to +separate ligands. The system simulates differential activity of the +ligands on the signalling of IL-6. +This affects Signal Transducer and Activator of +Transcription 3 (STAT3) activity on the production of +biomarker C-Reactive Protein (CRP) expression. +
Figures referring to this Crohn's Disease model are 3a, 4d, +4e, 4f and 5b. +
+
+

This model is described in the article:

+
+ A multiscale model of + interleukin-6-mediated immune regulation in Crohn's disease and + its application in drug discovery and development. +
+
Dwivedi G, Fitz L, Hegen M, Martin + SW, Harrold J, Heatherington A, Li C.
+
CPT Pharmacometrics Syst Pharmacol + 2014; 3: e89
+

Abstract:

+
+

In this study, we have developed a multiscale systems model + of interleukin (IL)-6-mediated immune regulation in Crohn's + disease, by integrating intracellular signaling with + organ-level dynamics of pharmacological markers underlying the + disease. This model was linked to a general pharmacokinetic + model for therapeutic monoclonal antibodies and used to + comparatively study various biotherapeutic strategies targeting + IL-6-mediated signaling in Crohn's disease. Our work + illustrates techniques to develop mechanistic models of disease + biology to study drug-system interaction. Despite a sparse + training data set, predictions of the model were qualitatively + validated by clinical biomarker data from a pilot trial with + tocilizumab. Model-based analysis suggests that strategies + targeting IL-6, IL-6R?, or the IL-6/sIL-6R? complex are less + effective at suppressing pharmacological markers of Crohn's + than dual targeting the IL-6/sIL-6R? complex in addition to + IL-6 or IL-6R?. The potential value of multiscale system + pharmacology modeling in drug discovery and development is also + discussed.CPT: Pharmacometrics & Systems Pharmacology + (2014) 3, e89; doi:10.1038/psp.2013.64; advance online + publication 8 January 2014.

+
+
+
+

This model is hosted on + BioModels Database + and identified by: + BIOMD0000000537.

+

To cite BioModels Database, please use: + BioModels Database: + An enhanced, curated and annotated resource for published + quantitative kinetic models.

+
+
+

To the extent possible under law, all copyright and related or + neighbouring rights to this encoded model have been dedicated to + the public domain worldwide. Please refer to + CC0 + Public Domain Dedication for more information.

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With HepG2 cell volume of 2.8 pL/cell, this translates to 0.0685 nM/hr. Since this rate in terms of concentration is independent of cell volume, it can be used directly for cells with different volumes but similar receptor dynamics. + + + + + + + 1/hr + +Estimated from drug PK models + + + + + + + + + + + + 2014-07-18T13:02:16Z + + + + + + + + + + 18 nM/hr + + + + + + + + 2014-07-18T13:02:16Z + + + + + + + + + + + + + + + 2014-07-31T13:31:32Z + + + + + + + + + + 1/hr + + + + + + + nM + +Commonly used model of protein synthesis: +mRNA: dm/dt = Sm*TF/(C + TF) - Dm*m +Protein: dn/dt = Sn*m - Dn*n +Solving for st. st: n(ss) = (Sn/Dn)*(Sm/Dm)*TF/(C+TF) +VmProtSynth = (Sn/Dn)*(Sm/Dm) = 4875000 +KmProtSynth = C = 108 +The parameters are obtained from Moya et al. (2010), who estimate these parameters for IL6 signaling. +The actual value used may be different, as it was optimized to fit the data + + + + + + + + + + + + + + 2014-07-31T13:31:30Z + + + + + + + + + + + + + + + + + + 2014-07-31T13:31:28Z + + + + + + + + + + + + + + + 2014-07-31T13:31:31Z + + + + + + + + + + + 1/hr + +Slow receptor shedding driven by CRP. The parameter has been calculated, along with the basal sR synthesis rate, to get +sR = 1.6, when CRP = 40 (HV); and +sR = 2.8, when CRP = 2000 (CD). + + + + + + + + + + + 2014-07-31T13:32:02Z + + + + + + + + + + + + + + + 2014-07-18T11:24:13Z + + + + + + + + + + + + + + + 2014-07-18T11:08:30Z + + + + + + + + + + + + + + + + + + + + 2014-08-01T12:26:51Z + + + + + + + + + + + + + + + + 2014-07-18T13:02:16Z + + + + + + + + + + + + + + + + + + + + 2014-07-31T13:32:07Z + + + + + + + + + + + + + + + 2014-07-18T11:08:44Z + + + + + + + + + + + + + + + 2014-08-01T12:08:30Z + + + + + + + + + + + + + + + + + + + + + + + + + + + + + mw434adaf5_cef0_4a33_9ad2_a4e49e1fd825 + mw2c605ff5_50f5_45f2_a70c_53fcd866d14c + + + + + + + + mw434adaf5_cef0_4a33_9ad2_a4e49e1fd825 + mwc691d0d1_8c1b_4ce4_85c6_1315c42e97b1 + + + + + + + + mw6a5e10a9_d442_4dde_8ec3_6a26c9807374 + mw2c605ff5_50f5_45f2_a70c_53fcd866d14c + + + + + + + + mw6a5e10a9_d442_4dde_8ec3_6a26c9807374 + mwa8283449_0e21_41a1_baac_ebf697b3555a + 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mw03db56ac_8dc6_4931_ae82_fef706d2ee3d + mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + mwf626e95e_543f_41e4_aad4_c6bf60ab345b + + + + + + + + + + + + + + + + + + + + + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + Function_for_reaction_2 + kgp130Off + kgp130On + mw03db56ac_8dc6_4931_ae82_fef706d2ee3d + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + mw810ff751_fa4e_4143_bd50_169b3e325e1e + mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 + + + + + + + + + + + + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + Function_for_reaction_3 + kIL6Synth + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + + + + + + + + + + + + + + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + Function_for_reaction_4 + kIL6Decay + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + mwf626e95e_543f_41e4_aad4_c6bf60ab345b + + + + + + + + + + + + + 2014-07-31T13:31:25Z + + + + + + + + + + + + + + + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + Function_for_reaction_5 + kCRPDecay + mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + + + + + + + + + + + + + + + + + + + + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + Function_for_reaction_6 + kgp130Off + kgp130On + mw4638f126_8cb8_4021_ab41_6ae195743ba0 + mw80848184_e2dd_47ce_86d7_7a21479342bd + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a + + + + + + + + + + + + + + + + + + + + + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + Function_for_reaction_7 + kRLOff + kRLOn + mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 + mw10315fa3_6f13_4618_bda8_a8694bd3c374 + mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + + + + + 2014-08-01T12:29:08Z + + + + + + + + + + + + + + + + + + + + + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + Function_for_reaction_8 + kgp130Off + kgp130On + mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 + mw80848184_e2dd_47ce_86d7_7a21479342bd + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + 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Dwivedi2014 - Crohns IL6 Disease model - +Anti-IL6R Antibody
+
This model is comprised of four models: +
+ Possible avenues for Interleukin-6 (IL-6) inhibition in +treating Crohn's disease are compared here. Each model refers to +separate ligands. The system simulates differential activity of the +ligands on the signalling of IL-6. +This affects Signal Transducer and Activator of +Transcription 3 (STAT3) activity on the production of +biomarker C-Reactive Protein (CRP) expression. +
Figures referring to this Crohn's Disease model are 3a, 4d, +4e, 4f and 5b. +
+
+

This model is described in the article:

+
+ A multiscale model of + interleukin-6-mediated immune regulation in Crohn's disease and + its application in drug discovery and development. +
+
Dwivedi G, Fitz L, Hegen M, Martin + SW, Harrold J, Heatherington A, Li C.
+
CPT Pharmacometrics Syst Pharmacol + 2014; 3: e89
+

Abstract:

+
+

In this study, we have developed a multiscale systems model + of interleukin (IL)-6-mediated immune regulation in Crohn's + disease, by integrating intracellular signaling with + organ-level dynamics of pharmacological markers underlying the + disease. This model was linked to a general pharmacokinetic + model for therapeutic monoclonal antibodies and used to + comparatively study various biotherapeutic strategies targeting + IL-6-mediated signaling in Crohn's disease. Our work + illustrates techniques to develop mechanistic models of disease + biology to study drug-system interaction. Despite a sparse + training data set, predictions of the model were qualitatively + validated by clinical biomarker data from a pilot trial with + tocilizumab. Model-based analysis suggests that strategies + targeting IL-6, IL-6R?, or the IL-6/sIL-6R? complex are less + effective at suppressing pharmacological markers of Crohn's + than dual targeting the IL-6/sIL-6R? complex in addition to + IL-6 or IL-6R?. The potential value of multiscale system + pharmacology modeling in drug discovery and development is also + discussed.CPT: Pharmacometrics & Systems Pharmacology + (2014) 3, e89; doi:10.1038/psp.2013.64; advance online + publication 8 January 2014.

+
+
+
+

This model is hosted on + BioModels Database + and identified by: + BIOMD0000000537.

+

To cite BioModels Database, please use: + BioModels Database: + An enhanced, curated and annotated resource for published + quantitative kinetic models.

+
+
+

To the extent possible under law, all copyright and related or + neighbouring rights to this encoded model have been dedicated to + the public domain worldwide. Please refer to + CC0 + Public Domain Dedication for more information.

+
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mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + mwa09d6284_843e_404e_abbb_052fbb535197 + + + + + + + + mwa09d6284_843e_404e_abbb_052fbb535197 + mw3667a5e1_02c9_44a0_acb4_b0431faa822d + mw10315fa3_6f13_4618_bda8_a8694bd3c374 + + + + mw1c4bc9c3_52ad_4ef7_bf7f_97b0e2101ead + mw772cbf20_3fc1_4800_ae59_77884f1ae333 + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + kRsynth + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + kRsynth + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + mw6cce2109_0e32_4dd9_98ec_41173e8ef07d + + + mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 + + + mwf44f7f27_5bb1_4c7f_8964_560fa5e1743a + + + + + + mwf44f7f27_5bb1_4c7f_8964_560fa5e1743a + mw6cce2109_0e32_4dd9_98ec_41173e8ef07d + + mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 + + + + + + + + + kRLOff + + + kRLOn + + + mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 + + + mw10315fa3_6f13_4618_bda8_a8694bd3c374 + + + mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + kRLOn + mw10315fa3_6f13_4618_bda8_a8694bd3c374 + mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 + + + + kRLOff + mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + kgp130Off + + + kgp130On + + + mw4638f126_8cb8_4021_ab41_6ae195743ba0 + + + mw80848184_e2dd_47ce_86d7_7a21479342bd + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a + + + + + + + + kgp130On + mw4638f126_8cb8_4021_ab41_6ae195743ba0 + mw80848184_e2dd_47ce_86d7_7a21479342bd + + + + kgp130Off + mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + kRdeg + + + mw10315fa3_6f13_4618_bda8_a8694bd3c374 + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + kRdeg + mw10315fa3_6f13_4618_bda8_a8694bd3c374 + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + kRLOff + + + kRLOn + + + mw03db56ac_8dc6_4931_ae82_fef706d2ee3d + + + mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + + mwf626e95e_543f_41e4_aad4_c6bf60ab345b + + + + + + + + kRLOn + mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc + mwf626e95e_543f_41e4_aad4_c6bf60ab345b + + + + kRLOff + mw03db56ac_8dc6_4931_ae82_fef706d2ee3d + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + + + + + + + + mw862f1480_c60c_4863_a565_b2c1c77e238e + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + mwd5313618_89eb_4c8c_bc82_66f10f966349 + + + + + + mw862f1480_c60c_4863_a565_b2c1c77e238e + mwd5313618_89eb_4c8c_bc82_66f10f966349 + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + mw1c4bc9c3_52ad_4ef7_bf7f_97b0e2101ead + + + mw2e464cf3_a09c_4b7c_9f3c_06720016a48e + + + mw3667a5e1_02c9_44a0_acb4_b0431faa822d + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + mwa09d6284_843e_404e_abbb_052fbb535197 + + + mwf405687b_7401_44ec_a0d6_4a2b35c13e8a + + + + + + + + mwa09d6284_843e_404e_abbb_052fbb535197 + mw3667a5e1_02c9_44a0_acb4_b0431faa822d + mw2e464cf3_a09c_4b7c_9f3c_06720016a48e + + + + mw1c4bc9c3_52ad_4ef7_bf7f_97b0e2101ead + mwf405687b_7401_44ec_a0d6_4a2b35c13e8a + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + mw3667a5e1_02c9_44a0_acb4_b0431faa822d + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30 + + + + + + mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30 + mw3667a5e1_02c9_44a0_acb4_b0431faa822d + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + mw0eb6c959_d408_45a0_a450_928b8c5876bb + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + mwf44f7f27_5bb1_4c7f_8964_560fa5e1743a + + + + + + mwf44f7f27_5bb1_4c7f_8964_560fa5e1743a + mw0eb6c959_d408_45a0_a450_928b8c5876bb + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + kIL6Synth + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + + + kIL6Synth + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + + + + + + + + mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + + mw88a75379_f9a1_4acc_baeb_94c32bb736a5 + + + + + + mw88a75379_f9a1_4acc_baeb_94c32bb736a5 + mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 2014-07-31T13:31:31Z + + + + + + + + + + 1/hr +Kd = 50 pM + + + + + + + + + + + + 2014-07-31T13:31:33Z + + + + + + + + + + nM/hr + +Estimated at 115 receptor/cell/hr using the receptor model for HepG2 cells. With HepG2 cell volume of 2.8 pL/cell, this translates to 0.0685 nM/hr. Since this rate in terms of concentration is independent of cell volume, it can be used directly for cells with different volumes but similar receptor dynamics. + + + + + + + 1/hr + +Estimated from drug PK models + + + + + + + + + + + + 2014-07-18T13:02:16Z + + + + + + + + + + 18 nM/hr + + + + + + + + 2014-07-18T13:02:16Z + + + + + + + + + + + + + + + 2014-07-31T13:31:32Z + + + + + + + + + + 1/hr + + + + + + + nM + +Commonly used model of protein synthesis: +mRNA: dm/dt = Sm*TF/(C + TF) - Dm*m +Protein: dn/dt = Sn*m - Dn*n +Solving for st. st: n(ss) = (Sn/Dn)*(Sm/Dm)*TF/(C+TF) +VmProtSynth = (Sn/Dn)*(Sm/Dm) = 4875000 +KmProtSynth = C = 108 +The parameters are obtained from Moya et al. (2010), who estimate these parameters for IL6 signaling. +The actual value used may be different, as it was optimized to fit the data + + + + + + + + + + + + + + 2014-07-31T13:31:30Z + + + + + + + + + + + + + + + + + + 2014-07-31T13:31:28Z + + + + + + + + + + + + + + + 2014-07-31T13:31:31Z + + + + + + + + + + + 1/hr + +Slow receptor shedding driven by CRP. The parameter has been calculated, along with the basal sR synthesis rate, to get +sR = 1.6, when CRP = 40 (HV); and +sR = 2.8, when CRP = 2000 (CD). + + + + + + + + + + + 2014-07-31T13:32:02Z + + + + + + + + + + + + + + + 2014-07-18T11:24:13Z + + + + + + + + + + + + + + + 2014-07-18T11:08:30Z + + + + + + + + + + + + + + + + + + + + 2014-08-01T12:26:51Z + + + + + + + + + + + + + + + + 2014-07-18T13:02:16Z + + + + + + + + + + + + + + + + + + + + 2014-07-31T13:32:07Z + + + + + + + + + + + + + + + 2014-07-18T11:08:44Z + + + + + + + + + + + + + + + 2014-08-01T12:08:30Z + + + + + + + + + + + + + + + + + + + + + + + + + + + + + mw434adaf5_cef0_4a33_9ad2_a4e49e1fd825 + mw2c605ff5_50f5_45f2_a70c_53fcd866d14c + + + + + + + + mw434adaf5_cef0_4a33_9ad2_a4e49e1fd825 + mwc691d0d1_8c1b_4ce4_85c6_1315c42e97b1 + + + + + + + + mw6a5e10a9_d442_4dde_8ec3_6a26c9807374 + mw2c605ff5_50f5_45f2_a70c_53fcd866d14c + + + + + + + + mw6a5e10a9_d442_4dde_8ec3_6a26c9807374 + mwa8283449_0e21_41a1_baac_ebf697b3555a + 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mw03db56ac_8dc6_4931_ae82_fef706d2ee3d + mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + mwf626e95e_543f_41e4_aad4_c6bf60ab345b + + + + + + + + + + + + + + + + + + + + + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + Function_for_reaction_2 + kgp130Off + kgp130On + mw03db56ac_8dc6_4931_ae82_fef706d2ee3d + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + mw810ff751_fa4e_4143_bd50_169b3e325e1e + mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 + + + + + + + + + + + + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + Function_for_reaction_3 + kIL6Synth + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + + + + + + + + + + + + + + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + Function_for_reaction_4 + kIL6Decay + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + mwf626e95e_543f_41e4_aad4_c6bf60ab345b + + + + + + + + + + + + + 2014-07-31T13:31:25Z + + + + + + + + + + + + + + + + + mw53ffe9e6_beef_45c4_90a5_a79197ed506e + + Function_for_reaction_5 + kCRPDecay + 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Dwivedi2014 - Crohns IL6 Disease model - +Anti-IL6R Antibody
+
This model is comprised of four models: +
+Possible avenues for Interleukin-6 (IL-6) inhibition in +treating Crohn's disease are compared here. Each model refers to +separate ligands. The system simulates differential activity of the +ligands on the signalling of IL-6. +This affects Signal Transducer and Activator of +Transcription 3 (STAT3) activity on the production of +biomarker C-Reactive Protein (CRP) expression. +
Figures referring to this Crohn's Disease model are 3a, 4d, +4e, 4f and 5b. +
+
+

This model is described in the article:

+
+ A multiscale model of + interleukin-6-mediated immune regulation in Crohn's disease and + its application in drug discovery and development. +
+
Dwivedi G, Fitz L, Hegen M, Martin + SW, Harrold J, Heatherington A, Li C.
+
CPT Pharmacometrics Syst Pharmacol + 2014; 3: e89
+

Abstract:

+
+

In this study, we have developed a multiscale systems model + of interleukin (IL)-6-mediated immune regulation in Crohn's + disease, by integrating intracellular signaling with + organ-level dynamics of pharmacological markers underlying the + disease. This model was linked to a general pharmacokinetic + model for therapeutic monoclonal antibodies and used to + comparatively study various biotherapeutic strategies targeting + IL-6-mediated signaling in Crohn's disease. Our work + illustrates techniques to develop mechanistic models of disease + biology to study drug-system interaction. Despite a sparse + training data set, predictions of the model were qualitatively + validated by clinical biomarker data from a pilot trial with + tocilizumab. Model-based analysis suggests that strategies + targeting IL-6, IL-6R?, or the IL-6/sIL-6R? complex are less + effective at suppressing pharmacological markers of Crohn's + than dual targeting the IL-6/sIL-6R? complex in addition to + IL-6 or IL-6R?. The potential value of multiscale system + pharmacology modeling in drug discovery and development is also + discussed.CPT: Pharmacometrics & Systems Pharmacology + (2014) 3, e89; doi:10.1038/psp.2013.64; advance online + publication 8 January 2014.

+
+
+
+

This model is hosted on + BioModels Database + and identified by: + BIOMD0000000537.

+

To cite BioModels Database, please use: + BioModels Database: + An enhanced, curated and annotated resource for published + quantitative kinetic models.

+
+
+

To the extent possible under law, all copyright and related or + neighbouring rights to this encoded model have been dedicated to + the public domain worldwide. Please refer to + CC0 + Public Domain Dedication for more information.

+
+ + + + + + + + + 2014-07-18T11:04:10Z + + + + + + + + + + + + Knight-Schrijver + Vincent + + vknight@ebi.ac.uk + + EMBL-EBI + + + + + + 2014-08-06T11:45:54Z + + + 2017-01-13T16:03:17Z + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + kRint + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a + + + + + + kRint + mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + kgp130Off + + + kgp130On + + + mw147d30ec_478e_4090_b496_128a131d29eb + + + mw4638f126_8cb8_4021_ab41_6ae195743ba0 + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + mwab41493c_6349_45f1_a226_3030cfed0e06 + + + + + + + + kgp130On + mw4638f126_8cb8_4021_ab41_6ae195743ba0 + mw147d30ec_478e_4090_b496_128a131d29eb + + + + kgp130Off + mwab41493c_6349_45f1_a226_3030cfed0e06 + + + mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e + + + + + + + + + kRLOff + + + kRLOn + + + 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With HepG2 cell volume of 2.8 pL/cell, this translates to 0.0685 nM/hr. Since this rate in terms of concentration is independent of cell volume, it can be used directly for cells with different volumes but similar receptor dynamics. + + + + + + + 1/hr + +Estimated from drug PK models + + + + + + + + + + + + 2014-07-18T13:02:16Z + + + + + + + + + + 18 nM/hr + + + + + + + + 2014-07-18T13:02:16Z + + + + + + + + + + + + + + + 2014-07-31T13:31:32Z + + + + + + + + + + 1/hr + + + + + + + nM + +Commonly used model of protein synthesis: +mRNA: dm/dt = Sm*TF/(C + TF) - Dm*m +Protein: dn/dt = Sn*m - Dn*n +Solving for st. st: n(ss) = (Sn/Dn)*(Sm/Dm)*TF/(C+TF) +VmProtSynth = (Sn/Dn)*(Sm/Dm) = 4875000 +KmProtSynth = C = 108 +The parameters are obtained from Moya et al. (2010), who estimate these parameters for IL6 signaling. +The actual value used may be different, as it was optimized to fit the data + + + + + + + + + + + + + + 2014-07-31T13:31:30Z + + + + + + + + + + + + + + + + + + 2014-07-31T13:31:28Z + + + + + + + + + + + + + + + 2014-07-31T13:31:31Z + + + + + + + + + + + 1/hr + +Slow receptor shedding driven by CRP. 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zt2Y|5#&Mb=Nm@&IYVr85!L@l&mcITU)=2%bhGTDKMX7zoi)K0O`0C|kwa)X(=THCg LFHht4=THA1F8`Z! literal 0 HcmV?d00001 diff --git a/notebook/pdf_keywords.txt b/notebook/pdf_keywords.txt new file mode 100644 index 00000000..f8e68536 --- /dev/null +++ b/notebook/pdf_keywords.txt @@ -0,0 +1 @@ +Crohn's disease, Interleukin-6 (IL-6), T-cells \ No newline at end of file diff --git a/notebook/sbml_rag_notebook.ipynb b/notebook/sbml_rag_notebook.ipynb new file mode 100644 index 00000000..790ecb75 --- /dev/null +++ b/notebook/sbml_rag_notebook.ipynb @@ -0,0 +1,287 @@ +{ + "cells": [ + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "# SBML Model RAG System for Background Knowledge Extraction\n", + "\n", + "This notebook demonstrates how to extract background knowledge for species in an SBML model using a RAG (Retrieval Augmented Generation) approach with LangChain and OpenAI.\n", + "\n", + "**What this notebook does:**\n", + "1. Loads and processes a PDF containing background information\n", + "2. Extracts key concepts/keywords from the PDF\n", + "3. Parses an SBML model to identify species\n", + "4. Uses RAG to generate background knowledge for each species\n", + "5. Returns two lists: species background knowledge and PDF keywords" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## 1. Install Required Packages\n", + "\n", + "First, let's make sure we have all the required packages installed." + ] + }, + { + "cell_type": "code", + "execution_count": 1, + "metadata": {}, + "outputs": [], + "source": [ + "# Uncomment to install required packages if not already installed\n", + "# !pip install langchain langchain-openai langchain-community faiss-cpu python-libsbml pypdf" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## 2. Import the SBML RAG Utilities" + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "metadata": {}, + "outputs": [], + "source": [ + "# Import the utilities from our custom module\n", + "import sys\n", + "sys.path.append('/Users/U1013680/workplace/projects/inigoo18/AIAgents4Pharma/notebook')\n", + "from sbml_rag_utils import process_sbml_and_pdf\n", + "import os\n", + "import pandas as pd" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## 3. Setup File Paths and API Key" + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "metadata": {}, + "outputs": [], + "source": [ + "# Set your OpenAI API key\n", + "\n", + "# Get the API key from environment variables\n", + "openai_api_key = os.environ.get(\"OPENAI_API_KEY\")\n", + "\n", + "# Check if the key exists\n", + "if openai_api_key is None:\n", + " raise ValueError(\"The OPENAI_API_KEY environment variable is not set\")\n", + "\n", + "# Define file paths\n", + "sbml_file_path = \"./data/Dwivedi_Model537_empty.xml\" # Replace with your SBML file path\n", + "pdf_file_path = \"./data/psp201364a.pdf\" # Replace with your PDF file path\n", + "\n", + "# Verify files exist\n", + "assert os.path.exists(sbml_file_path), f\"SBML file not found at {sbml_file_path}\"\n", + "assert os.path.exists(pdf_file_path), f\"PDF file not found at {pdf_file_path}\"" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## 4. Process the SBML Model and PDF\n", + "\n", + "Now we'll run the main processing function to extract species background knowledge and PDF keywords." + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Analyzing SBML model species...\n", + "Found 44 species in the model\n", + "Species are distributed across 4 compartments\n", + "Loading and processing PDF...\n", + "Extracting keywords from PDF...\n", + "Parsing SBML model for species...\n", + "Extracting background information for 44 species...\n", + "Processing species 1/44: IL6\n", + "Processing species 2/44: sgp130\n", + "Processing species 3/44: sR_IL6_sgp130\n", + "Processing species 4/44: CRP\n", + "Processing species 5/44: sR\n", + "Processing species 6/44: sR_IL6\n", + "Processing species 7/44: Ab\n", + "Processing species 8/44: Ab_sR\n", + "Processing species 9/44: Ab_sR_IL6\n", + "Processing species 10/44: CRP Suppression (%)\n", + "Processing species 11/44: CRP (% of baseline)\n", + "Processing species 12/44: gp130\n", + "Processing species 13/44: R_IL6_gp130\n", + "Processing species 14/44: sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n" + ] + } + ], + "source": [ + "# Process the SBML model and PDF\n", + "species_backgrounds, keywords = process_sbml_and_pdf(\n", + " sbml_file_path=sbml_file_path,\n", + " pdf_file_path=pdf_file_path,\n", + " api_key=openai_api_key,\n", + " max_species=10 \n", + ")" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## 5. Display the Results\n", + "\n", + "### 5.1 PDF Keywords" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "print(\"PDF Keywords:\")\n", + "for i, keyword in enumerate(keywords, 1):\n", + " print(f\"{i}. {keyword}\")" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### 5.2 Species Background Knowledge" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Create a DataFrame for better visualization\n", + "species_df = pd.DataFrame(species_backgrounds)\n", + "species_df" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### 5.3 Detailed Species Information" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Display detailed information for each species\n", + "for i, species in enumerate(species_backgrounds, 1):\n", + " print(f\"\\n{'='*80}\\n{i}. {species['name']} (ID: {species['id']})\\n{'='*80}\")\n", + " print(species['background'])" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## 6. Save Results to Files (Optional)" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# Save species background information to CSV\n", + "species_df.to_csv(\"species_backgrounds.csv\", index=False)\n", + "\n", + "# Save keywords to a text file\n", + "with open(\"pdf_keywords.txt\", \"w\") as f:\n", + " f.write(\", \".join(keywords))\n", + "\n", + "print(\"Results saved to 'species_backgrounds.csv' and 'pdf_keywords.txt'\")" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## 7. Return the Required Lists\n", + "\n", + "Here are the two lists that were requested:" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# List 1: Species background knowledge\n", + "species_backgrounds" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [ + "# List 2: PDF keywords\n", + "keywords" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [] + } + ], + "metadata": { + "kernelspec": { + "display_name": "Python 3", + "language": "python", + "name": "python3" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.11.11" + } + }, + "nbformat": 4, + "nbformat_minor": 4 +} diff --git a/notebook/sbml_rag_utils.py b/notebook/sbml_rag_utils.py new file mode 100644 index 00000000..8ad68b97 --- /dev/null +++ b/notebook/sbml_rag_utils.py @@ -0,0 +1,288 @@ +import os +from langchain_openai import OpenAIEmbeddings, ChatOpenAI +from langchain_community.document_loaders import PyPDFLoader +from langchain_text_splitters import RecursiveCharacterTextSplitter +from langchain_core.prompts import PromptTemplate +from langchain_core.output_parsers import StrOutputParser +from langchain_core.runnables import RunnablePassthrough +from langchain_community.vectorstores import FAISS +import libsbml + + +def analyze_model_species(sbml_file_path): + """ + Analyzes the SBML model and returns statistics about species in the model. + + Args: + sbml_file_path (str): Path to the SBML model file + + Returns: + dict: Statistics about species in the model + """ + reader = libsbml.SBMLReader() + document = reader.readSBML(sbml_file_path) + + # Check for errors + if document.getNumErrors() > 0: + print(f"Errors in SBML document: {document.getNumErrors()}") + return {"error": f"Errors in SBML document: {document.getNumErrors()}"} + + model = document.getModel() + + # Get species count + species_count = model.getNumSpecies() + + # Get species details + species_details = [] + compartment_distribution = {} + duplicate_names = {} + + for s in range(species_count): + species_obj = model.getSpecies(s) + species_id = species_obj.getId() + species_name = species_obj.getName() or species_id + compartment = species_obj.getCompartment() + + # Track duplicated names + if species_name in duplicate_names: + duplicate_names[species_name] += 1 + else: + duplicate_names[species_name] = 1 + + # Track compartment distribution + if compartment in compartment_distribution: + compartment_distribution[compartment] += 1 + else: + compartment_distribution[compartment] = 1 + + # Track if species has initial concentration or amount + has_initial_amount = species_obj.isSetInitialAmount() + has_initial_concentration = species_obj.isSetInitialConcentration() + + species_details.append({ + 'id': species_id, + 'name': species_name, + 'compartment': compartment, + 'has_initial_amount': has_initial_amount, + 'has_initial_concentration': has_initial_concentration + }) + + # Filter duplicate names + duplicate_name_counts = {name: count for name, count in duplicate_names.items() if count > 1} + + # Get model units if available + substance_units = model.getSubstanceUnits() if model.isSetSubstanceUnits() else "Not specified" + time_units = model.getTimeUnits() if model.isSetTimeUnits() else "Not specified" + + # Generate summary statistics + statistics = { + "total_species_count": species_count, + "compartment_distribution": compartment_distribution, + "substance_units": substance_units, + "time_units": time_units, + "species_details": species_details, + "duplicate_names": duplicate_name_counts, + "duplicate_name_count": len(duplicate_name_counts), + "species_with_initial_amount": sum(1 for s in species_details if s['has_initial_amount']), + "species_with_initial_concentration": sum(1 for s in species_details if s['has_initial_concentration']) + } + + return statistics + +def load_and_process_pdf(pdf_path): + """Load PDF and create searchable vector database""" + # Load the PDF + loader = PyPDFLoader(pdf_path) + documents = loader.load() + + # Split documents into chunks + text_splitter = RecursiveCharacterTextSplitter( + chunk_size=1000, + chunk_overlap=200 + ) + splits = text_splitter.split_documents(documents) + + # Create vector store + embeddings = OpenAIEmbeddings() + vectorstore = FAISS.from_documents(splits, embeddings) + + return vectorstore, documents + +def extract_keywords_from_pdf(documents): + """Extract the top 3 biomedical entity keywords from the PDF""" + llm = ChatOpenAI(model="gpt-4o") + + # Combine all document content + full_text = "" + for doc in documents: + full_text += doc.page_content + "\n" + + # Create a prompt for keyword extraction focusing on biomedical entities + prompt = PromptTemplate.from_template( + """You are given a scientific document related to a systems biology model. + Extract exactly THREE key biomedical entities that best represent the main focus of this document. + + FOCUS ONLY ON: + - Disease names (e.g., Alzheimer's disease, cancer, diabetes) + - Gene or protein names (e.g., TNF-alpha, P53, BRCA1) + - Pathways or biological processes (e.g., apoptosis, inflammation) + - Cell types or tissues (e.g., T-cells, hepatocytes) + - Drug classes or specific drugs (e.g., statins, metformin) + + DO NOT INCLUDE general methodologies, modeling approaches, or broad fields of study. + + Format your response as a comma-separated list. + Document: + {text} + + THREE BIOMEDICAL ENTITY KEYWORDS:""" + ) + + # Create and run the chain + chain = prompt | llm | StrOutputParser() + keywords = chain.invoke({"text": full_text[:10000]}) # Use first 10000 chars if doc is very large + + # Process the result to get a clean list + keyword_list = [k.strip() for k in keywords.split(',')] + return keyword_list[:3] # Ensure we get exactly 3 keywords + +def parse_sbml_model(sbml_file_path): + """Parse SBML model and extract species only, handling duplicate names""" + reader = libsbml.SBMLReader() + document = reader.readSBML(sbml_file_path) + + # Check for errors + if document.getNumErrors() > 0: + print(f"Errors in SBML document: {document.getNumErrors()}") + return [] + + model = document.getModel() + + # Extract species (molecules, proteins, etc.) + species = [] + species_names = {} # Track name occurrence count + + for s in range(model.getNumSpecies()): + species_obj = model.getSpecies(s) + species_id = species_obj.getId() + species_name = species_obj.getName() or species_id + compartment = species_obj.getCompartment() + + # Check if this name already exists and append compartment or count if needed + if species_name in species_names: + species_names[species_name] += 1 + # Make the name unique by adding compartment and count + unique_name = f"{species_name} ({compartment}, #{species_names[species_name]})" + else: + species_names[species_name] = 1 + unique_name = species_name + + species.append({ + 'id': species_id, + 'name': unique_name, + 'original_name': species_name, + 'compartment': compartment, + 'type': 'species' + }) + + return species + +def get_species_background(species, vectorstore): + """Get background information for a specific species""" + llm = ChatOpenAI(model="gpt-4o") + + # Create a retriever for relevant information + retriever = vectorstore.as_retriever(search_kwargs={"k": 3}) + + # Use original name for searching but include ID for clarity + search_name = species.get('original_name', species['name']) + display_name = species['name'] + species_id = species['id'] + compartment = species.get('compartment', 'unknown compartment') + + # Define the RAG prompt + template = """You are a systems biology expert assistant. Based on the provided context, + extract and summarize relevant background information about the species named '{species_name}' + (ID: {species_id}, located in {compartment}). + + Focus on information about this specific biological species/molecule, including: + - Its biological function + - Its role in pathways + - Any interactions with other molecules + - Its importance in the biological system being modeled + + If there is no specific information about this species in the context, infer what it might be based on + general knowledge about similar biological components in the context described. + + Context: + {context} + + Background information about {species_name}:""" + + prompt = PromptTemplate.from_template(template) + + # The query to search for in the vectorstore - use original name for better matching + query_text = f"Information about {search_name}" + + # Create the RAG pipeline with correct input handling + rag_chain = ( + { + "context": retriever, + "species_name": lambda _: display_name, + "species_id": lambda _: species_id, + "compartment": lambda _: compartment + } + | prompt + | llm + | StrOutputParser() + ) + + # Run the chain with the correct string query instead of a dict + background = rag_chain.invoke(query_text) + + return { + "id": species_id, + "name": display_name, + "original_name": search_name, + "compartment": compartment, + "background": background + } + +def process_sbml_and_pdf(sbml_file_path, pdf_file_path, api_key=None, max_species=None): + """Main function to process SBML model and extract background information for species""" + # Set OpenAI API key if provided + if api_key: + os.environ["OPENAI_API_KEY"] = api_key + + # First, analyze the model to get species statistics + print("Analyzing SBML model species...") + species_stats = analyze_model_species(sbml_file_path) + print(f"Found {species_stats['total_species_count']} species in the model") + print(f"Species are distributed across {len(species_stats['compartment_distribution'])} compartments") + + # Load and process PDF + print("Loading and processing PDF...") + vectorstore, documents = load_and_process_pdf(pdf_file_path) + + # Extract keywords from PDF + print("Extracting keywords from PDF...") + keywords = extract_keywords_from_pdf(documents) + + # Parse SBML model to get species + print("Parsing SBML model for species...") + species_list = parse_sbml_model(sbml_file_path) + + # Limit the number of species to process if specified + if max_species and max_species < len(species_list): + print(f"Limiting processing to {max_species} species (out of {len(species_list)} total)") + species_list = species_list[:max_species] + + # Get background information for each species + print(f"Extracting background information for {len(species_list)} species...") + species_backgrounds = [] + for i, species in enumerate(species_list): + print(f"Processing species {i+1}/{len(species_list)}: {species['name']}") + background_info = get_species_background(species, vectorstore) + species_backgrounds.append(background_info) + + return species_backgrounds, keywords, species_stats \ No newline at end of file diff --git a/notebook/species_backgrounds.csv b/notebook/species_backgrounds.csv new file mode 100644 index 00000000..15e043e9 --- /dev/null +++ b/notebook/species_backgrounds.csv @@ -0,0 +1,19 @@ +id,name,original_name,compartment,background +mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Interleukin-6 (IL-6) is a cytokine that plays a significant role in the immune system and has been implicated in various inflammatory diseases, including Crohn’s disease. In the context of Crohn's disease, IL-6 is identified as an important factor contributing to enhanced T-cell survival and resistance to apoptosis in the lamina propria, which is a part of the intestinal mucosa. This activity is associated with increased chemokine secretion, which can exacerbate the inflammatory response. + +IL-6 signaling can occur via two pathways: the classical signaling pathway and the trans-signaling pathway. The classical pathway is mediated by the membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor, forming a complex that ultimately leads to the activation of Janus kinase (Jak) proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation. The trans-signaling pathway is particularly relevant in disease states because it allows IL-6 to exert effects even in cells that do not express the membrane-bound IL-6Rα. + +In therapeutic contexts, antibodies targeting IL-6 or IL-6Rα can modulate IL-6 signaling. For instance, the anti-IL-6Rα antibody tocilizumab is used in the treatment of diseases like rheumatoid arthritis. In modeling studies, differences in the pharmacokinetics and interactions of anti-IL-6 and anti-IL-6Rα antibodies have been observed, with studies showing that certain antibodies can effectively suppress IL-6 signaling and alter the dose-response curves of these interactions. + +Overall, IL-6 is an important molecule in the biological system being modeled, particularly in the context of immune regulation and inflammatory diseases. Its signaling pathways and interactions with other molecules are critical to understanding the disease mechanisms and developing therapeutic interventions." +mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130,sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context from the document, the species 'sgp130' is described as a molecule involved in the inhibition of IL-6 trans-signaling. This characterization stems from its fusion form, sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is utilized to explore therapeutic applications, such as for conditions like Crohn’s disease. Here are the key points regarding sgp130: + +1. **Biological Function**: sgp130 functions primarily as an inhibitor of IL-6 trans-signaling. This signaling pathway is significant because it mediates inflammation and is implicated in various inflammatory diseases. The role of sgp130 in natural physiology appears to involve the regulation or modulation of IL-6 signaling pathways by binding to the IL-6/sIL-6Rα complex. + +2. **Role in Pathways**: sgp130 is involved in the IL-6 signaling pathway. It functions to compete with, and hence regulate, IL-6 and its receptor (sIL-6Rα). This regulation is important because excessive IL-6 signaling is associated with inflammatory conditions. + +3. **Interactions with Other Molecules**: sgp130 interacts specifically with the IL-6/sIL-6Rα complex, indicating a competition for binding that can attenuate downstream signaling effects typically mediated by this complex. This interaction is a critical component of its inhibitory action. + +4. **Importance in the Biological System Being Modeled**: While sgp130 is present at high concentrations compared to free IL-6, the sensitivity analyses from the models suggest that small changes in sgp130 levels have minimal effects on the system dynamics due to its high baseline level. Its impact seems to be less pronounced under typical physiological conditions; however, it can be significant under therapeutic conditions when used in high doses as sgp130Fc. + +Overall, sgp130 plays a regulatory role in the IL-6 pathway, and its therapeutic potential lies in its ability to inhibit IL-6 trans-signaling, albeit requiring high and frequent dosing for effectiveness in models such as Crohn's disease." From 38f1ac156fe4d8ad9e26f3dbe7f921d8f841ad0a Mon Sep 17 00:00:00 2001 From: ShengZhaoDE Date: Fri, 7 Mar 2025 12:18:45 +0100 Subject: [PATCH 04/14] add comments --- notebook/sbml_rag_notebook.ipynb | 211 ++++++++++++++++++++++++++----- 1 file changed, 178 insertions(+), 33 deletions(-) diff --git a/notebook/sbml_rag_notebook.ipynb b/notebook/sbml_rag_notebook.ipynb index 790ecb75..56db0331 100644 --- a/notebook/sbml_rag_notebook.ipynb +++ b/notebook/sbml_rag_notebook.ipynb @@ -20,9 +20,7 @@ "cell_type": "markdown", "metadata": {}, "source": [ - "## 1. Install Required Packages\n", - "\n", - "First, let's make sure we have all the required packages installed." + "## 1. Install Required Packages" ] }, { @@ -98,7 +96,7 @@ }, { "cell_type": "code", - "execution_count": 4, + "execution_count": 5, "metadata": {}, "outputs": [ { @@ -111,31 +109,20 @@ "Loading and processing PDF...\n", "Extracting keywords from PDF...\n", "Parsing SBML model for species...\n", - "Extracting background information for 44 species...\n", - "Processing species 1/44: IL6\n", - "Processing species 2/44: sgp130\n", - "Processing species 3/44: sR_IL6_sgp130\n", - "Processing species 4/44: CRP\n", - "Processing species 5/44: sR\n", - "Processing species 6/44: sR_IL6\n", - "Processing species 7/44: Ab\n", - "Processing species 8/44: Ab_sR\n", - "Processing species 9/44: Ab_sR_IL6\n", - "Processing species 10/44: CRP Suppression (%)\n", - "Processing species 11/44: CRP (% of baseline)\n", - "Processing species 12/44: gp130\n", - "Processing species 13/44: R_IL6_gp130\n", - "Processing species 14/44: sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n" + "Limiting processing to 2 species (out of 44 total)\n", + "Extracting background information for 2 species...\n", + "Processing species 1/2: IL6\n", + "Processing species 2/2: sgp130\n" ] } ], "source": [ "# Process the SBML model and PDF\n", - "species_backgrounds, keywords = process_sbml_and_pdf(\n", + "species_backgrounds, keywords, species_stats = process_sbml_and_pdf(\n", " sbml_file_path=sbml_file_path,\n", " pdf_file_path=pdf_file_path,\n", " api_key=openai_api_key,\n", - " max_species=10 \n", + " max_species=2\n", ")" ] }, @@ -150,9 +137,20 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 6, "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "PDF Keywords:\n", + "1. Crohn's disease\n", + "2. Interleukin-6 (IL-6)\n", + "3. T-cells\n" + ] + } + ], "source": [ "print(\"PDF Keywords:\")\n", "for i, keyword in enumerate(keywords, 1):\n", @@ -168,9 +166,77 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 7, "metadata": {}, - "outputs": [], + "outputs": [ + { + "data": { + "text/html": [ + "

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1mwbbbce920_e8dd_4320_9386_fc94bfb2fc99sgp130sgp130mw53ffe9e6_beef_45c4_90a5_a79197ed506eBased on the provided context from the documen...
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" + ], + "text/plain": [ + " id name original_name \\\n", + "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 IL6 \n", + "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130 sgp130 \n", + "\n", + " compartment \\\n", + "0 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "1 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "\n", + " background \n", + "0 Interleukin-6 (IL-6) is a cytokine that plays ... \n", + "1 Based on the provided context from the documen... " + ] + }, + "execution_count": 7, + "metadata": {}, + "output_type": "execute_result" + } + ], "source": [ "# Create a DataFrame for better visualization\n", "species_df = pd.DataFrame(species_backgrounds)\n", @@ -186,9 +252,42 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 8, "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "\n", + "================================================================================\n", + "1. IL6 (ID: mwf626e95e_543f_41e4_aad4_c6bf60ab345b)\n", + "================================================================================\n", + "Interleukin-6 (IL-6) is a cytokine that plays a significant role in the immune system and has been implicated in various inflammatory diseases, including Crohn’s disease. In the context of Crohn's disease, IL-6 is identified as an important factor contributing to enhanced T-cell survival and resistance to apoptosis in the lamina propria, which is a part of the intestinal mucosa. This activity is associated with increased chemokine secretion, which can exacerbate the inflammatory response.\n", + "\n", + "IL-6 signaling can occur via two pathways: the classical signaling pathway and the trans-signaling pathway. The classical pathway is mediated by the membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor, forming a complex that ultimately leads to the activation of Janus kinase (Jak) proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation. The trans-signaling pathway is particularly relevant in disease states because it allows IL-6 to exert effects even in cells that do not express the membrane-bound IL-6Rα.\n", + "\n", + "In therapeutic contexts, antibodies targeting IL-6 or IL-6Rα can modulate IL-6 signaling. For instance, the anti-IL-6Rα antibody tocilizumab is used in the treatment of diseases like rheumatoid arthritis. In modeling studies, differences in the pharmacokinetics and interactions of anti-IL-6 and anti-IL-6Rα antibodies have been observed, with studies showing that certain antibodies can effectively suppress IL-6 signaling and alter the dose-response curves of these interactions.\n", + "\n", + "Overall, IL-6 is an important molecule in the biological system being modeled, particularly in the context of immune regulation and inflammatory diseases. Its signaling pathways and interactions with other molecules are critical to understanding the disease mechanisms and developing therapeutic interventions.\n", + "\n", + "================================================================================\n", + "2. sgp130 (ID: mwbbbce920_e8dd_4320_9386_fc94bfb2fc99)\n", + "================================================================================\n", + "Based on the provided context from the document, the species 'sgp130' is described as a molecule involved in the inhibition of IL-6 trans-signaling. This characterization stems from its fusion form, sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is utilized to explore therapeutic applications, such as for conditions like Crohn’s disease. Here are the key points regarding sgp130:\n", + "\n", + "1. **Biological Function**: sgp130 functions primarily as an inhibitor of IL-6 trans-signaling. This signaling pathway is significant because it mediates inflammation and is implicated in various inflammatory diseases. The role of sgp130 in natural physiology appears to involve the regulation or modulation of IL-6 signaling pathways by binding to the IL-6/sIL-6Rα complex.\n", + "\n", + "2. **Role in Pathways**: sgp130 is involved in the IL-6 signaling pathway. It functions to compete with, and hence regulate, IL-6 and its receptor (sIL-6Rα). This regulation is important because excessive IL-6 signaling is associated with inflammatory conditions.\n", + "\n", + "3. **Interactions with Other Molecules**: sgp130 interacts specifically with the IL-6/sIL-6Rα complex, indicating a competition for binding that can attenuate downstream signaling effects typically mediated by this complex. This interaction is a critical component of its inhibitory action.\n", + "\n", + "4. **Importance in the Biological System Being Modeled**: While sgp130 is present at high concentrations compared to free IL-6, the sensitivity analyses from the models suggest that small changes in sgp130 levels have minimal effects on the system dynamics due to its high baseline level. Its impact seems to be less pronounced under typical physiological conditions; however, it can be significant under therapeutic conditions when used in high doses as sgp130Fc.\n", + "\n", + "Overall, sgp130 plays a regulatory role in the IL-6 pathway, and its therapeutic potential lies in its ability to inhibit IL-6 trans-signaling, albeit requiring high and frequent dosing for effectiveness in models such as Crohn's disease.\n" + ] + } + ], "source": [ "# Display detailed information for each species\n", "for i, species in enumerate(species_backgrounds, 1):\n", @@ -205,9 +304,17 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 9, "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Results saved to 'species_backgrounds.csv' and 'pdf_keywords.txt'\n" + ] + } + ], "source": [ "# Save species background information to CSV\n", "species_df.to_csv(\"species_backgrounds.csv\", index=False)\n", @@ -230,9 +337,29 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 10, "metadata": {}, - "outputs": [], + "outputs": [ + { + "data": { + "text/plain": [ + "[{'id': 'mwf626e95e_543f_41e4_aad4_c6bf60ab345b',\n", + " 'name': 'IL6',\n", + " 'original_name': 'IL6',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': \"Interleukin-6 (IL-6) is a cytokine that plays a significant role in the immune system and has been implicated in various inflammatory diseases, including Crohn’s disease. In the context of Crohn's disease, IL-6 is identified as an important factor contributing to enhanced T-cell survival and resistance to apoptosis in the lamina propria, which is a part of the intestinal mucosa. This activity is associated with increased chemokine secretion, which can exacerbate the inflammatory response.\\n\\nIL-6 signaling can occur via two pathways: the classical signaling pathway and the trans-signaling pathway. The classical pathway is mediated by the membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor, forming a complex that ultimately leads to the activation of Janus kinase (Jak) proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation. The trans-signaling pathway is particularly relevant in disease states because it allows IL-6 to exert effects even in cells that do not express the membrane-bound IL-6Rα.\\n\\nIn therapeutic contexts, antibodies targeting IL-6 or IL-6Rα can modulate IL-6 signaling. For instance, the anti-IL-6Rα antibody tocilizumab is used in the treatment of diseases like rheumatoid arthritis. In modeling studies, differences in the pharmacokinetics and interactions of anti-IL-6 and anti-IL-6Rα antibodies have been observed, with studies showing that certain antibodies can effectively suppress IL-6 signaling and alter the dose-response curves of these interactions.\\n\\nOverall, IL-6 is an important molecule in the biological system being modeled, particularly in the context of immune regulation and inflammatory diseases. Its signaling pathways and interactions with other molecules are critical to understanding the disease mechanisms and developing therapeutic interventions.\"},\n", + " {'id': 'mwbbbce920_e8dd_4320_9386_fc94bfb2fc99',\n", + " 'name': 'sgp130',\n", + " 'original_name': 'sgp130',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': \"Based on the provided context from the document, the species 'sgp130' is described as a molecule involved in the inhibition of IL-6 trans-signaling. This characterization stems from its fusion form, sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is utilized to explore therapeutic applications, such as for conditions like Crohn’s disease. Here are the key points regarding sgp130:\\n\\n1. **Biological Function**: sgp130 functions primarily as an inhibitor of IL-6 trans-signaling. This signaling pathway is significant because it mediates inflammation and is implicated in various inflammatory diseases. The role of sgp130 in natural physiology appears to involve the regulation or modulation of IL-6 signaling pathways by binding to the IL-6/sIL-6Rα complex.\\n\\n2. **Role in Pathways**: sgp130 is involved in the IL-6 signaling pathway. It functions to compete with, and hence regulate, IL-6 and its receptor (sIL-6Rα). This regulation is important because excessive IL-6 signaling is associated with inflammatory conditions.\\n\\n3. **Interactions with Other Molecules**: sgp130 interacts specifically with the IL-6/sIL-6Rα complex, indicating a competition for binding that can attenuate downstream signaling effects typically mediated by this complex. This interaction is a critical component of its inhibitory action.\\n\\n4. **Importance in the Biological System Being Modeled**: While sgp130 is present at high concentrations compared to free IL-6, the sensitivity analyses from the models suggest that small changes in sgp130 levels have minimal effects on the system dynamics due to its high baseline level. Its impact seems to be less pronounced under typical physiological conditions; however, it can be significant under therapeutic conditions when used in high doses as sgp130Fc.\\n\\nOverall, sgp130 plays a regulatory role in the IL-6 pathway, and its therapeutic potential lies in its ability to inhibit IL-6 trans-signaling, albeit requiring high and frequent dosing for effectiveness in models such as Crohn's disease.\"}]" + ] + }, + "execution_count": 10, + "metadata": {}, + "output_type": "execute_result" + } + ], "source": [ "# List 1: Species background knowledge\n", "species_backgrounds" @@ -240,9 +367,20 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 11, "metadata": {}, - "outputs": [], + "outputs": [ + { + "data": { + "text/plain": [ + "[\"Crohn's disease\", 'Interleukin-6 (IL-6)', 'T-cells']" + ] + }, + "execution_count": 11, + "metadata": {}, + "output_type": "execute_result" + } + ], "source": [ "# List 2: PDF keywords\n", "keywords" @@ -255,6 +393,13 @@ "outputs": [], "source": [] }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [] + }, { "cell_type": "code", "execution_count": null, From 1e6ddddb90672164b2968c5926c4e71e02c0597c Mon Sep 17 00:00:00 2001 From: ShengZhaoDE Date: Fri, 7 Mar 2025 12:35:26 +0100 Subject: [PATCH 05/14] update function to get top 20 keyword for a pdf file --- notebook/sbml_rag_notebook.ipynb | 2 +- notebook/sbml_rag_utils.py | 2 +- 2 files changed, 2 insertions(+), 2 deletions(-) diff --git a/notebook/sbml_rag_notebook.ipynb b/notebook/sbml_rag_notebook.ipynb index 56db0331..c02df8a9 100644 --- a/notebook/sbml_rag_notebook.ipynb +++ b/notebook/sbml_rag_notebook.ipynb @@ -122,7 +122,7 @@ " sbml_file_path=sbml_file_path,\n", " pdf_file_path=pdf_file_path,\n", " api_key=openai_api_key,\n", - " max_species=2\n", + " max_species=44\n", ")" ] }, diff --git a/notebook/sbml_rag_utils.py b/notebook/sbml_rag_utils.py index 8ad68b97..3ea55b88 100644 --- a/notebook/sbml_rag_utils.py +++ b/notebook/sbml_rag_utils.py @@ -144,7 +144,7 @@ def extract_keywords_from_pdf(documents): # Process the result to get a clean list keyword_list = [k.strip() for k in keywords.split(',')] - return keyword_list[:3] # Ensure we get exactly 3 keywords + return keyword_list[:20] # Ensure we get top keywords def parse_sbml_model(sbml_file_path): """Parse SBML model and extract species only, handling duplicate names""" From b557498359c40eefd30fb1e70b193faa24052603 Mon Sep 17 00:00:00 2001 From: ShengZhaoDE Date: Fri, 7 Mar 2025 12:48:07 +0100 Subject: [PATCH 06/14] update prompt to get top 20 keyword from a PDF file --- notebook/pdf_keywords.txt | 2 +- notebook/sbml_rag_notebook.ipynb | 132 ++++++++++++++++++------------- notebook/sbml_rag_utils.py | 6 +- notebook/species_backgrounds.csv | 29 ++++--- 4 files changed, 95 insertions(+), 74 deletions(-) diff --git a/notebook/pdf_keywords.txt b/notebook/pdf_keywords.txt index f8e68536..cbcee156 100644 --- a/notebook/pdf_keywords.txt +++ b/notebook/pdf_keywords.txt @@ -1 +1 @@ -Crohn's disease, Interleukin-6 (IL-6), T-cells \ No newline at end of file +Crohn's disease, interleukin (IL)-6, IL-6 receptor (IL-6Rα), soluble IL-6 receptor (sIL-6Rα), Janus kinase (Jak), signal transducer and activator of transcription 3 (STAT3), T-cells, hepatocytes, chemokines, C-reactive protein (CRP), gp130, trans-signaling, classical signaling, apoptosis, inflammation, acute-phase proteins, sIL-6Rα complex, pSTAT3, interleukin-6 receptor, cis-signaling pathway \ No newline at end of file diff --git a/notebook/sbml_rag_notebook.ipynb b/notebook/sbml_rag_notebook.ipynb index c02df8a9..0cd74c9c 100644 --- a/notebook/sbml_rag_notebook.ipynb +++ b/notebook/sbml_rag_notebook.ipynb @@ -96,7 +96,7 @@ }, { "cell_type": "code", - "execution_count": 5, + "execution_count": 4, "metadata": {}, "outputs": [ { @@ -109,10 +109,9 @@ "Loading and processing PDF...\n", "Extracting keywords from PDF...\n", "Parsing SBML model for species...\n", - "Limiting processing to 2 species (out of 44 total)\n", - "Extracting background information for 2 species...\n", - "Processing species 1/2: IL6\n", - "Processing species 2/2: sgp130\n" + "Limiting processing to 1 species (out of 44 total)\n", + "Extracting background information for 1 species...\n", + "Processing species 1/1: IL6\n" ] } ], @@ -122,7 +121,7 @@ " sbml_file_path=sbml_file_path,\n", " pdf_file_path=pdf_file_path,\n", " api_key=openai_api_key,\n", - " max_species=44\n", + " max_species=1\n", ")" ] }, @@ -137,7 +136,7 @@ }, { "cell_type": "code", - "execution_count": 6, + "execution_count": 5, "metadata": {}, "outputs": [ { @@ -146,8 +145,25 @@ "text": [ "PDF Keywords:\n", "1. Crohn's disease\n", - "2. Interleukin-6 (IL-6)\n", - "3. T-cells\n" + "2. interleukin (IL)-6\n", + "3. IL-6 receptor (IL-6Rα)\n", + "4. soluble IL-6 receptor (sIL-6Rα)\n", + "5. Janus kinase (Jak)\n", + "6. signal transducer and activator of transcription 3 (STAT3)\n", + "7. T-cells\n", + "8. hepatocytes\n", + "9. chemokines\n", + "10. C-reactive protein (CRP)\n", + "11. gp130\n", + "12. trans-signaling\n", + "13. classical signaling\n", + "14. apoptosis\n", + "15. inflammation\n", + "16. acute-phase proteins\n", + "17. sIL-6Rα complex\n", + "18. pSTAT3\n", + "19. interleukin-6 receptor\n", + "20. cis-signaling pathway\n" ] } ], @@ -166,7 +182,7 @@ }, { "cell_type": "code", - "execution_count": 7, + "execution_count": 6, "metadata": {}, "outputs": [ { @@ -204,35 +220,24 @@ " IL6\n", " IL6\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " Interleukin-6 (IL-6) is a cytokine that plays ...\n", - " \n", - " \n", - " 1\n", - " mwbbbce920_e8dd_4320_9386_fc94bfb2fc99\n", - " sgp130\n", - " sgp130\n", - " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " Based on the provided context from the documen...\n", + " The species named 'IL6' in the provided contex...\n", " \n", " \n", "\n", "" ], "text/plain": [ - " id name original_name \\\n", - "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 IL6 \n", - "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130 sgp130 \n", + " id name original_name \\\n", + "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 IL6 \n", "\n", " compartment \\\n", "0 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", - "1 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", "\n", " background \n", - "0 Interleukin-6 (IL-6) is a cytokine that plays ... \n", - "1 Based on the provided context from the documen... " + "0 The species named 'IL6' in the provided contex... " ] }, - "execution_count": 7, + "execution_count": 6, "metadata": {}, "output_type": "execute_result" } @@ -252,7 +257,7 @@ }, { "cell_type": "code", - "execution_count": 8, + "execution_count": 7, "metadata": {}, "outputs": [ { @@ -263,28 +268,27 @@ "================================================================================\n", "1. IL6 (ID: mwf626e95e_543f_41e4_aad4_c6bf60ab345b)\n", "================================================================================\n", - "Interleukin-6 (IL-6) is a cytokine that plays a significant role in the immune system and has been implicated in various inflammatory diseases, including Crohn’s disease. In the context of Crohn's disease, IL-6 is identified as an important factor contributing to enhanced T-cell survival and resistance to apoptosis in the lamina propria, which is a part of the intestinal mucosa. This activity is associated with increased chemokine secretion, which can exacerbate the inflammatory response.\n", - "\n", - "IL-6 signaling can occur via two pathways: the classical signaling pathway and the trans-signaling pathway. The classical pathway is mediated by the membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor, forming a complex that ultimately leads to the activation of Janus kinase (Jak) proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation. The trans-signaling pathway is particularly relevant in disease states because it allows IL-6 to exert effects even in cells that do not express the membrane-bound IL-6Rα.\n", - "\n", - "In therapeutic contexts, antibodies targeting IL-6 or IL-6Rα can modulate IL-6 signaling. For instance, the anti-IL-6Rα antibody tocilizumab is used in the treatment of diseases like rheumatoid arthritis. In modeling studies, differences in the pharmacokinetics and interactions of anti-IL-6 and anti-IL-6Rα antibodies have been observed, with studies showing that certain antibodies can effectively suppress IL-6 signaling and alter the dose-response curves of these interactions.\n", - "\n", - "Overall, IL-6 is an important molecule in the biological system being modeled, particularly in the context of immune regulation and inflammatory diseases. Its signaling pathways and interactions with other molecules are critical to understanding the disease mechanisms and developing therapeutic interventions.\n", - "\n", - "================================================================================\n", - "2. sgp130 (ID: mwbbbce920_e8dd_4320_9386_fc94bfb2fc99)\n", - "================================================================================\n", - "Based on the provided context from the document, the species 'sgp130' is described as a molecule involved in the inhibition of IL-6 trans-signaling. This characterization stems from its fusion form, sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is utilized to explore therapeutic applications, such as for conditions like Crohn’s disease. Here are the key points regarding sgp130:\n", + "The species named 'IL6' in the provided context likely refers to the cytokine Interleukin-6, which plays a crucial role in the immune system.\n", "\n", - "1. **Biological Function**: sgp130 functions primarily as an inhibitor of IL-6 trans-signaling. This signaling pathway is significant because it mediates inflammation and is implicated in various inflammatory diseases. The role of sgp130 in natural physiology appears to involve the regulation or modulation of IL-6 signaling pathways by binding to the IL-6/sIL-6Rα complex.\n", + "### Biological Function:\n", + "- **Interleukin-6 (IL-6)** is a cytokine, a type of signaling molecule in the immune system, involved in inflammation and infection responses, as well as the regulation of metabolic, regenerative, and neural processes.\n", "\n", - "2. **Role in Pathways**: sgp130 is involved in the IL-6 signaling pathway. It functions to compete with, and hence regulate, IL-6 and its receptor (sIL-6Rα). This regulation is important because excessive IL-6 signaling is associated with inflammatory conditions.\n", + "### Role in Pathways:\n", + "- IL-6 is essential in **immune regulation**, particularly in inflammatory responses. \n", + "- It signals via two main pathways:\n", + " - **Classical Pathway**: Involves the membrane-bound IL-6 receptor (IL-6Rα), where IL-6 binds to the IL-6Rα, and this complex recruits the membrane-bound co-receptor gp130, forming a heterotrimer, which subsequently dimerizes into an active hexameric complex.\n", + " - **Trans-Signaling Pathway**: Involves the soluble IL-6 receptor (sIL-6Rα), where a preformed IL-6/sIL-6Rα complex in the circulation interacts with gp130 on the cell surface, allowing cells that do not express the IL-6Rα on their surface to respond to IL-6.\n", "\n", - "3. **Interactions with Other Molecules**: sgp130 interacts specifically with the IL-6/sIL-6Rα complex, indicating a competition for binding that can attenuate downstream signaling effects typically mediated by this complex. This interaction is a critical component of its inhibitory action.\n", + "### Interactions with Other Molecules:\n", + "- IL-6 interacts with **IL-6Rα** (both membrane-bound and soluble) and the co-receptor **gp130**, leading to activation of intracellular signaling cascades, primarily involving the **Janus kinase (Jak) family** proteins and subsequent phosphorylation of **signal transducer and activator of transcription 3 (STAT3)**.\n", + "- Antibodies targeting IL-6, such as in therapeutics, can affect these interactions and pathways, influencing the immune response and highlighting their use in treatments for diseases like rheumatoid arthritis and potentially Crohn's disease.\n", "\n", - "4. **Importance in the Biological System Being Modeled**: While sgp130 is present at high concentrations compared to free IL-6, the sensitivity analyses from the models suggest that small changes in sgp130 levels have minimal effects on the system dynamics due to its high baseline level. Its impact seems to be less pronounced under typical physiological conditions; however, it can be significant under therapeutic conditions when used in high doses as sgp130Fc.\n", + "### Importance in the Biological System Being Modeled:\n", + "- In the context of **Crohn's Disease**, IL-6 is a significant player in exacerbating disease symptoms by promoting T-cell survival and resistance to apoptosis, thus contributing to chronic inflammation.\n", + "- IL-6 signaling increases chemokine secretion, further amplifying inflammatory responses.\n", + "- Its pathways are critical targets for therapeutic interventions aiming to modulate immune responses and alleviate disease symptoms.\n", "\n", - "Overall, sgp130 plays a regulatory role in the IL-6 pathway, and its therapeutic potential lies in its ability to inhibit IL-6 trans-signaling, albeit requiring high and frequent dosing for effectiveness in models such as Crohn's disease.\n" + "Overall, IL-6 is a multifunctional cytokine, pivotal in immune regulation, inflammation, and cellular signaling, making it a critical focus for therapeutic targeting in various inflammatory diseases.\n" ] } ], @@ -299,12 +303,12 @@ "cell_type": "markdown", "metadata": {}, "source": [ - "## 6. Save Results to Files (Optional)" + "## 6. Save Results to Files" ] }, { "cell_type": "code", - "execution_count": 9, + "execution_count": 8, "metadata": {}, "outputs": [ { @@ -337,7 +341,7 @@ }, { "cell_type": "code", - "execution_count": 10, + "execution_count": 9, "metadata": {}, "outputs": [ { @@ -347,15 +351,10 @@ " 'name': 'IL6',\n", " 'original_name': 'IL6',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"Interleukin-6 (IL-6) is a cytokine that plays a significant role in the immune system and has been implicated in various inflammatory diseases, including Crohn’s disease. In the context of Crohn's disease, IL-6 is identified as an important factor contributing to enhanced T-cell survival and resistance to apoptosis in the lamina propria, which is a part of the intestinal mucosa. This activity is associated with increased chemokine secretion, which can exacerbate the inflammatory response.\\n\\nIL-6 signaling can occur via two pathways: the classical signaling pathway and the trans-signaling pathway. The classical pathway is mediated by the membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor, forming a complex that ultimately leads to the activation of Janus kinase (Jak) proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation. The trans-signaling pathway is particularly relevant in disease states because it allows IL-6 to exert effects even in cells that do not express the membrane-bound IL-6Rα.\\n\\nIn therapeutic contexts, antibodies targeting IL-6 or IL-6Rα can modulate IL-6 signaling. For instance, the anti-IL-6Rα antibody tocilizumab is used in the treatment of diseases like rheumatoid arthritis. In modeling studies, differences in the pharmacokinetics and interactions of anti-IL-6 and anti-IL-6Rα antibodies have been observed, with studies showing that certain antibodies can effectively suppress IL-6 signaling and alter the dose-response curves of these interactions.\\n\\nOverall, IL-6 is an important molecule in the biological system being modeled, particularly in the context of immune regulation and inflammatory diseases. Its signaling pathways and interactions with other molecules are critical to understanding the disease mechanisms and developing therapeutic interventions.\"},\n", - " {'id': 'mwbbbce920_e8dd_4320_9386_fc94bfb2fc99',\n", - " 'name': 'sgp130',\n", - " 'original_name': 'sgp130',\n", - " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"Based on the provided context from the document, the species 'sgp130' is described as a molecule involved in the inhibition of IL-6 trans-signaling. This characterization stems from its fusion form, sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is utilized to explore therapeutic applications, such as for conditions like Crohn’s disease. Here are the key points regarding sgp130:\\n\\n1. **Biological Function**: sgp130 functions primarily as an inhibitor of IL-6 trans-signaling. This signaling pathway is significant because it mediates inflammation and is implicated in various inflammatory diseases. The role of sgp130 in natural physiology appears to involve the regulation or modulation of IL-6 signaling pathways by binding to the IL-6/sIL-6Rα complex.\\n\\n2. **Role in Pathways**: sgp130 is involved in the IL-6 signaling pathway. It functions to compete with, and hence regulate, IL-6 and its receptor (sIL-6Rα). This regulation is important because excessive IL-6 signaling is associated with inflammatory conditions.\\n\\n3. **Interactions with Other Molecules**: sgp130 interacts specifically with the IL-6/sIL-6Rα complex, indicating a competition for binding that can attenuate downstream signaling effects typically mediated by this complex. This interaction is a critical component of its inhibitory action.\\n\\n4. **Importance in the Biological System Being Modeled**: While sgp130 is present at high concentrations compared to free IL-6, the sensitivity analyses from the models suggest that small changes in sgp130 levels have minimal effects on the system dynamics due to its high baseline level. Its impact seems to be less pronounced under typical physiological conditions; however, it can be significant under therapeutic conditions when used in high doses as sgp130Fc.\\n\\nOverall, sgp130 plays a regulatory role in the IL-6 pathway, and its therapeutic potential lies in its ability to inhibit IL-6 trans-signaling, albeit requiring high and frequent dosing for effectiveness in models such as Crohn's disease.\"}]" + " 'background': \"The species named 'IL6' in the provided context likely refers to the cytokine Interleukin-6, which plays a crucial role in the immune system.\\n\\n### Biological Function:\\n- **Interleukin-6 (IL-6)** is a cytokine, a type of signaling molecule in the immune system, involved in inflammation and infection responses, as well as the regulation of metabolic, regenerative, and neural processes.\\n\\n### Role in Pathways:\\n- IL-6 is essential in **immune regulation**, particularly in inflammatory responses. \\n- It signals via two main pathways:\\n - **Classical Pathway**: Involves the membrane-bound IL-6 receptor (IL-6Rα), where IL-6 binds to the IL-6Rα, and this complex recruits the membrane-bound co-receptor gp130, forming a heterotrimer, which subsequently dimerizes into an active hexameric complex.\\n - **Trans-Signaling Pathway**: Involves the soluble IL-6 receptor (sIL-6Rα), where a preformed IL-6/sIL-6Rα complex in the circulation interacts with gp130 on the cell surface, allowing cells that do not express the IL-6Rα on their surface to respond to IL-6.\\n\\n### Interactions with Other Molecules:\\n- IL-6 interacts with **IL-6Rα** (both membrane-bound and soluble) and the co-receptor **gp130**, leading to activation of intracellular signaling cascades, primarily involving the **Janus kinase (Jak) family** proteins and subsequent phosphorylation of **signal transducer and activator of transcription 3 (STAT3)**.\\n- Antibodies targeting IL-6, such as in therapeutics, can affect these interactions and pathways, influencing the immune response and highlighting their use in treatments for diseases like rheumatoid arthritis and potentially Crohn's disease.\\n\\n### Importance in the Biological System Being Modeled:\\n- In the context of **Crohn's Disease**, IL-6 is a significant player in exacerbating disease symptoms by promoting T-cell survival and resistance to apoptosis, thus contributing to chronic inflammation.\\n- IL-6 signaling increases chemokine secretion, further amplifying inflammatory responses.\\n- Its pathways are critical targets for therapeutic interventions aiming to modulate immune responses and alleviate disease symptoms.\\n\\nOverall, IL-6 is a multifunctional cytokine, pivotal in immune regulation, inflammation, and cellular signaling, making it a critical focus for therapeutic targeting in various inflammatory diseases.\"}]" ] }, - "execution_count": 10, + "execution_count": 9, "metadata": {}, "output_type": "execute_result" } @@ -367,16 +366,35 @@ }, { "cell_type": "code", - "execution_count": 11, + "execution_count": 10, "metadata": {}, "outputs": [ { "data": { "text/plain": [ - "[\"Crohn's disease\", 'Interleukin-6 (IL-6)', 'T-cells']" + "[\"Crohn's disease\",\n", + " 'interleukin (IL)-6',\n", + " 'IL-6 receptor (IL-6Rα)',\n", + " 'soluble IL-6 receptor (sIL-6Rα)',\n", + " 'Janus kinase (Jak)',\n", + " 'signal transducer and activator of transcription 3 (STAT3)',\n", + " 'T-cells',\n", + " 'hepatocytes',\n", + " 'chemokines',\n", + " 'C-reactive protein (CRP)',\n", + " 'gp130',\n", + " 'trans-signaling',\n", + " 'classical signaling',\n", + " 'apoptosis',\n", + " 'inflammation',\n", + " 'acute-phase proteins',\n", + " 'sIL-6Rα complex',\n", + " 'pSTAT3',\n", + " 'interleukin-6 receptor',\n", + " 'cis-signaling pathway']" ] }, - "execution_count": 11, + "execution_count": 10, "metadata": {}, "output_type": "execute_result" } diff --git a/notebook/sbml_rag_utils.py b/notebook/sbml_rag_utils.py index 3ea55b88..a0199c1f 100644 --- a/notebook/sbml_rag_utils.py +++ b/notebook/sbml_rag_utils.py @@ -109,7 +109,7 @@ def load_and_process_pdf(pdf_path): return vectorstore, documents def extract_keywords_from_pdf(documents): - """Extract the top 3 biomedical entity keywords from the PDF""" + """Extract the top biomedical entity keywords from the PDF""" llm = ChatOpenAI(model="gpt-4o") # Combine all document content @@ -120,7 +120,7 @@ def extract_keywords_from_pdf(documents): # Create a prompt for keyword extraction focusing on biomedical entities prompt = PromptTemplate.from_template( """You are given a scientific document related to a systems biology model. - Extract exactly THREE key biomedical entities that best represent the main focus of this document. + Extract exactly top thirty key biomedical entities that best represent the main focus of this document. FOCUS ONLY ON: - Disease names (e.g., Alzheimer's disease, cancer, diabetes) @@ -135,7 +135,7 @@ def extract_keywords_from_pdf(documents): Document: {text} - THREE BIOMEDICAL ENTITY KEYWORDS:""" + top thirty BIOMEDICAL ENTITY KEYWORDS:""" ) # Create and run the chain diff --git a/notebook/species_backgrounds.csv b/notebook/species_backgrounds.csv index 15e043e9..d6804df3 100644 --- a/notebook/species_backgrounds.csv +++ b/notebook/species_backgrounds.csv @@ -1,19 +1,22 @@ id,name,original_name,compartment,background -mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Interleukin-6 (IL-6) is a cytokine that plays a significant role in the immune system and has been implicated in various inflammatory diseases, including Crohn’s disease. In the context of Crohn's disease, IL-6 is identified as an important factor contributing to enhanced T-cell survival and resistance to apoptosis in the lamina propria, which is a part of the intestinal mucosa. This activity is associated with increased chemokine secretion, which can exacerbate the inflammatory response. +mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species named 'IL6' in the provided context likely refers to the cytokine Interleukin-6, which plays a crucial role in the immune system. -IL-6 signaling can occur via two pathways: the classical signaling pathway and the trans-signaling pathway. The classical pathway is mediated by the membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor, forming a complex that ultimately leads to the activation of Janus kinase (Jak) proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation. The trans-signaling pathway is particularly relevant in disease states because it allows IL-6 to exert effects even in cells that do not express the membrane-bound IL-6Rα. +### Biological Function: +- **Interleukin-6 (IL-6)** is a cytokine, a type of signaling molecule in the immune system, involved in inflammation and infection responses, as well as the regulation of metabolic, regenerative, and neural processes. -In therapeutic contexts, antibodies targeting IL-6 or IL-6Rα can modulate IL-6 signaling. For instance, the anti-IL-6Rα antibody tocilizumab is used in the treatment of diseases like rheumatoid arthritis. In modeling studies, differences in the pharmacokinetics and interactions of anti-IL-6 and anti-IL-6Rα antibodies have been observed, with studies showing that certain antibodies can effectively suppress IL-6 signaling and alter the dose-response curves of these interactions. +### Role in Pathways: +- IL-6 is essential in **immune regulation**, particularly in inflammatory responses. +- It signals via two main pathways: + - **Classical Pathway**: Involves the membrane-bound IL-6 receptor (IL-6Rα), where IL-6 binds to the IL-6Rα, and this complex recruits the membrane-bound co-receptor gp130, forming a heterotrimer, which subsequently dimerizes into an active hexameric complex. + - **Trans-Signaling Pathway**: Involves the soluble IL-6 receptor (sIL-6Rα), where a preformed IL-6/sIL-6Rα complex in the circulation interacts with gp130 on the cell surface, allowing cells that do not express the IL-6Rα on their surface to respond to IL-6. -Overall, IL-6 is an important molecule in the biological system being modeled, particularly in the context of immune regulation and inflammatory diseases. Its signaling pathways and interactions with other molecules are critical to understanding the disease mechanisms and developing therapeutic interventions." -mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130,sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context from the document, the species 'sgp130' is described as a molecule involved in the inhibition of IL-6 trans-signaling. This characterization stems from its fusion form, sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is utilized to explore therapeutic applications, such as for conditions like Crohn’s disease. Here are the key points regarding sgp130: +### Interactions with Other Molecules: +- IL-6 interacts with **IL-6Rα** (both membrane-bound and soluble) and the co-receptor **gp130**, leading to activation of intracellular signaling cascades, primarily involving the **Janus kinase (Jak) family** proteins and subsequent phosphorylation of **signal transducer and activator of transcription 3 (STAT3)**. +- Antibodies targeting IL-6, such as in therapeutics, can affect these interactions and pathways, influencing the immune response and highlighting their use in treatments for diseases like rheumatoid arthritis and potentially Crohn's disease. -1. **Biological Function**: sgp130 functions primarily as an inhibitor of IL-6 trans-signaling. This signaling pathway is significant because it mediates inflammation and is implicated in various inflammatory diseases. The role of sgp130 in natural physiology appears to involve the regulation or modulation of IL-6 signaling pathways by binding to the IL-6/sIL-6Rα complex. +### Importance in the Biological System Being Modeled: +- In the context of **Crohn's Disease**, IL-6 is a significant player in exacerbating disease symptoms by promoting T-cell survival and resistance to apoptosis, thus contributing to chronic inflammation. +- IL-6 signaling increases chemokine secretion, further amplifying inflammatory responses. +- Its pathways are critical targets for therapeutic interventions aiming to modulate immune responses and alleviate disease symptoms. -2. **Role in Pathways**: sgp130 is involved in the IL-6 signaling pathway. It functions to compete with, and hence regulate, IL-6 and its receptor (sIL-6Rα). This regulation is important because excessive IL-6 signaling is associated with inflammatory conditions. - -3. **Interactions with Other Molecules**: sgp130 interacts specifically with the IL-6/sIL-6Rα complex, indicating a competition for binding that can attenuate downstream signaling effects typically mediated by this complex. This interaction is a critical component of its inhibitory action. - -4. **Importance in the Biological System Being Modeled**: While sgp130 is present at high concentrations compared to free IL-6, the sensitivity analyses from the models suggest that small changes in sgp130 levels have minimal effects on the system dynamics due to its high baseline level. Its impact seems to be less pronounced under typical physiological conditions; however, it can be significant under therapeutic conditions when used in high doses as sgp130Fc. - -Overall, sgp130 plays a regulatory role in the IL-6 pathway, and its therapeutic potential lies in its ability to inhibit IL-6 trans-signaling, albeit requiring high and frequent dosing for effectiveness in models such as Crohn's disease." +Overall, IL-6 is a multifunctional cytokine, pivotal in immune regulation, inflammation, and cellular signaling, making it a critical focus for therapeutic targeting in various inflammatory diseases." From 1b51de9a73d26ba7e13438e84bf610e08c169b60 Mon Sep 17 00:00:00 2001 From: ShengZhaoDE Date: Fri, 7 Mar 2025 12:59:06 +0100 Subject: [PATCH 07/14] update keywords function --- notebook/pdf_keywords.txt | 2 +- notebook/sbml_rag_notebook.ipynb | 223 +++---------------------------- notebook/sbml_rag_utils.py | 40 +++++- notebook/species_backgrounds.csv | 22 +-- 4 files changed, 58 insertions(+), 229 deletions(-) diff --git a/notebook/pdf_keywords.txt b/notebook/pdf_keywords.txt index cbcee156..316e0ffa 100644 --- a/notebook/pdf_keywords.txt +++ b/notebook/pdf_keywords.txt @@ -1 +1 @@ -Crohn's disease, interleukin (IL)-6, IL-6 receptor (IL-6Rα), soluble IL-6 receptor (sIL-6Rα), Janus kinase (Jak), signal transducer and activator of transcription 3 (STAT3), T-cells, hepatocytes, chemokines, C-reactive protein (CRP), gp130, trans-signaling, classical signaling, apoptosis, inflammation, acute-phase proteins, sIL-6Rα complex, pSTAT3, interleukin-6 receptor, cis-signaling pathway \ No newline at end of file +Crohns disease, IL-6, T-cells, apoptosis, inflammation, IL-6Rα, sIL-6Rα, gp130, Jak, STAT3, CRP, hepatocytes, leukocytes, sgp130, tocilizumab, GI tract, liver, monoclonal antibodies, SOCS, circulation \ No newline at end of file diff --git a/notebook/sbml_rag_notebook.ipynb b/notebook/sbml_rag_notebook.ipynb index 0cd74c9c..a07aa4e0 100644 --- a/notebook/sbml_rag_notebook.ipynb +++ b/notebook/sbml_rag_notebook.ipynb @@ -25,7 +25,7 @@ }, { "cell_type": "code", - "execution_count": 1, + "execution_count": null, "metadata": {}, "outputs": [], "source": [ @@ -42,7 +42,7 @@ }, { "cell_type": "code", - "execution_count": 2, + "execution_count": null, "metadata": {}, "outputs": [], "source": [ @@ -51,7 +51,8 @@ "sys.path.append('/Users/U1013680/workplace/projects/inigoo18/AIAgents4Pharma/notebook')\n", "from sbml_rag_utils import process_sbml_and_pdf\n", "import os\n", - "import pandas as pd" + "import pandas as pd\n", + "import re" ] }, { @@ -63,7 +64,7 @@ }, { "cell_type": "code", - "execution_count": 3, + "execution_count": null, "metadata": {}, "outputs": [], "source": [ @@ -96,25 +97,9 @@ }, { "cell_type": "code", - "execution_count": 4, + "execution_count": null, "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "Analyzing SBML model species...\n", - "Found 44 species in the model\n", - "Species are distributed across 4 compartments\n", - "Loading and processing PDF...\n", - "Extracting keywords from PDF...\n", - "Parsing SBML model for species...\n", - "Limiting processing to 1 species (out of 44 total)\n", - "Extracting background information for 1 species...\n", - "Processing species 1/1: IL6\n" - ] - } - ], + "outputs": [], "source": [ "# Process the SBML model and PDF\n", "species_backgrounds, keywords, species_stats = process_sbml_and_pdf(\n", @@ -136,37 +121,9 @@ }, { "cell_type": "code", - "execution_count": 5, + "execution_count": null, "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "PDF Keywords:\n", - "1. Crohn's disease\n", - "2. interleukin (IL)-6\n", - "3. IL-6 receptor (IL-6Rα)\n", - "4. soluble IL-6 receptor (sIL-6Rα)\n", - "5. Janus kinase (Jak)\n", - "6. signal transducer and activator of transcription 3 (STAT3)\n", - "7. T-cells\n", - "8. hepatocytes\n", - "9. chemokines\n", - "10. C-reactive protein (CRP)\n", - "11. gp130\n", - "12. trans-signaling\n", - "13. classical signaling\n", - "14. apoptosis\n", - "15. inflammation\n", - "16. acute-phase proteins\n", - "17. sIL-6Rα complex\n", - "18. pSTAT3\n", - "19. interleukin-6 receptor\n", - "20. cis-signaling pathway\n" - ] - } - ], + "outputs": [], "source": [ "print(\"PDF Keywords:\")\n", "for i, keyword in enumerate(keywords, 1):\n", @@ -182,66 +139,9 @@ }, { "cell_type": "code", - "execution_count": 6, + "execution_count": null, "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
\n", - "\n", - "\n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - " \n", - "
idnameoriginal_namecompartmentbackground
0mwf626e95e_543f_41e4_aad4_c6bf60ab345bIL6IL6mw53ffe9e6_beef_45c4_90a5_a79197ed506eThe species named 'IL6' in the provided contex...
\n", - "
" - ], - "text/plain": [ - " id name original_name \\\n", - "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 IL6 \n", - "\n", - " compartment \\\n", - "0 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", - "\n", - " background \n", - "0 The species named 'IL6' in the provided contex... " - ] - }, - "execution_count": 6, - "metadata": {}, - "output_type": "execute_result" - } - ], + "outputs": [], "source": [ "# Create a DataFrame for better visualization\n", "species_df = pd.DataFrame(species_backgrounds)\n", @@ -257,41 +157,9 @@ }, { "cell_type": "code", - "execution_count": 7, + "execution_count": null, "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "\n", - "================================================================================\n", - "1. IL6 (ID: mwf626e95e_543f_41e4_aad4_c6bf60ab345b)\n", - "================================================================================\n", - "The species named 'IL6' in the provided context likely refers to the cytokine Interleukin-6, which plays a crucial role in the immune system.\n", - "\n", - "### Biological Function:\n", - "- **Interleukin-6 (IL-6)** is a cytokine, a type of signaling molecule in the immune system, involved in inflammation and infection responses, as well as the regulation of metabolic, regenerative, and neural processes.\n", - "\n", - "### Role in Pathways:\n", - "- IL-6 is essential in **immune regulation**, particularly in inflammatory responses. \n", - "- It signals via two main pathways:\n", - " - **Classical Pathway**: Involves the membrane-bound IL-6 receptor (IL-6Rα), where IL-6 binds to the IL-6Rα, and this complex recruits the membrane-bound co-receptor gp130, forming a heterotrimer, which subsequently dimerizes into an active hexameric complex.\n", - " - **Trans-Signaling Pathway**: Involves the soluble IL-6 receptor (sIL-6Rα), where a preformed IL-6/sIL-6Rα complex in the circulation interacts with gp130 on the cell surface, allowing cells that do not express the IL-6Rα on their surface to respond to IL-6.\n", - "\n", - "### Interactions with Other Molecules:\n", - "- IL-6 interacts with **IL-6Rα** (both membrane-bound and soluble) and the co-receptor **gp130**, leading to activation of intracellular signaling cascades, primarily involving the **Janus kinase (Jak) family** proteins and subsequent phosphorylation of **signal transducer and activator of transcription 3 (STAT3)**.\n", - "- Antibodies targeting IL-6, such as in therapeutics, can affect these interactions and pathways, influencing the immune response and highlighting their use in treatments for diseases like rheumatoid arthritis and potentially Crohn's disease.\n", - "\n", - "### Importance in the Biological System Being Modeled:\n", - "- In the context of **Crohn's Disease**, IL-6 is a significant player in exacerbating disease symptoms by promoting T-cell survival and resistance to apoptosis, thus contributing to chronic inflammation.\n", - "- IL-6 signaling increases chemokine secretion, further amplifying inflammatory responses.\n", - "- Its pathways are critical targets for therapeutic interventions aiming to modulate immune responses and alleviate disease symptoms.\n", - "\n", - "Overall, IL-6 is a multifunctional cytokine, pivotal in immune regulation, inflammation, and cellular signaling, making it a critical focus for therapeutic targeting in various inflammatory diseases.\n" - ] - } - ], + "outputs": [], "source": [ "# Display detailed information for each species\n", "for i, species in enumerate(species_backgrounds, 1):\n", @@ -308,17 +176,9 @@ }, { "cell_type": "code", - "execution_count": 8, + "execution_count": null, "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "Results saved to 'species_backgrounds.csv' and 'pdf_keywords.txt'\n" - ] - } - ], + "outputs": [], "source": [ "# Save species background information to CSV\n", "species_df.to_csv(\"species_backgrounds.csv\", index=False)\n", @@ -341,24 +201,9 @@ }, { "cell_type": "code", - "execution_count": 9, + "execution_count": null, "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "[{'id': 'mwf626e95e_543f_41e4_aad4_c6bf60ab345b',\n", - " 'name': 'IL6',\n", - " 'original_name': 'IL6',\n", - " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"The species named 'IL6' in the provided context likely refers to the cytokine Interleukin-6, which plays a crucial role in the immune system.\\n\\n### Biological Function:\\n- **Interleukin-6 (IL-6)** is a cytokine, a type of signaling molecule in the immune system, involved in inflammation and infection responses, as well as the regulation of metabolic, regenerative, and neural processes.\\n\\n### Role in Pathways:\\n- IL-6 is essential in **immune regulation**, particularly in inflammatory responses. \\n- It signals via two main pathways:\\n - **Classical Pathway**: Involves the membrane-bound IL-6 receptor (IL-6Rα), where IL-6 binds to the IL-6Rα, and this complex recruits the membrane-bound co-receptor gp130, forming a heterotrimer, which subsequently dimerizes into an active hexameric complex.\\n - **Trans-Signaling Pathway**: Involves the soluble IL-6 receptor (sIL-6Rα), where a preformed IL-6/sIL-6Rα complex in the circulation interacts with gp130 on the cell surface, allowing cells that do not express the IL-6Rα on their surface to respond to IL-6.\\n\\n### Interactions with Other Molecules:\\n- IL-6 interacts with **IL-6Rα** (both membrane-bound and soluble) and the co-receptor **gp130**, leading to activation of intracellular signaling cascades, primarily involving the **Janus kinase (Jak) family** proteins and subsequent phosphorylation of **signal transducer and activator of transcription 3 (STAT3)**.\\n- Antibodies targeting IL-6, such as in therapeutics, can affect these interactions and pathways, influencing the immune response and highlighting their use in treatments for diseases like rheumatoid arthritis and potentially Crohn's disease.\\n\\n### Importance in the Biological System Being Modeled:\\n- In the context of **Crohn's Disease**, IL-6 is a significant player in exacerbating disease symptoms by promoting T-cell survival and resistance to apoptosis, thus contributing to chronic inflammation.\\n- IL-6 signaling increases chemokine secretion, further amplifying inflammatory responses.\\n- Its pathways are critical targets for therapeutic interventions aiming to modulate immune responses and alleviate disease symptoms.\\n\\nOverall, IL-6 is a multifunctional cytokine, pivotal in immune regulation, inflammation, and cellular signaling, making it a critical focus for therapeutic targeting in various inflammatory diseases.\"}]" - ] - }, - "execution_count": 9, - "metadata": {}, - "output_type": "execute_result" - } - ], + "outputs": [], "source": [ "# List 1: Species background knowledge\n", "species_backgrounds" @@ -366,39 +211,9 @@ }, { "cell_type": "code", - "execution_count": 10, + "execution_count": null, "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "[\"Crohn's disease\",\n", - " 'interleukin (IL)-6',\n", - " 'IL-6 receptor (IL-6Rα)',\n", - " 'soluble IL-6 receptor (sIL-6Rα)',\n", - " 'Janus kinase (Jak)',\n", - " 'signal transducer and activator of transcription 3 (STAT3)',\n", - " 'T-cells',\n", - " 'hepatocytes',\n", - " 'chemokines',\n", - " 'C-reactive protein (CRP)',\n", - " 'gp130',\n", - " 'trans-signaling',\n", - " 'classical signaling',\n", - " 'apoptosis',\n", - " 'inflammation',\n", - " 'acute-phase proteins',\n", - " 'sIL-6Rα complex',\n", - " 'pSTAT3',\n", - " 'interleukin-6 receptor',\n", - " 'cis-signaling pathway']" - ] - }, - "execution_count": 10, - "metadata": {}, - "output_type": "execute_result" - } - ], + "outputs": [], "source": [ "# List 2: PDF keywords\n", "keywords" diff --git a/notebook/sbml_rag_utils.py b/notebook/sbml_rag_utils.py index a0199c1f..5dd03e68 100644 --- a/notebook/sbml_rag_utils.py +++ b/notebook/sbml_rag_utils.py @@ -7,6 +7,7 @@ from langchain_core.runnables import RunnablePassthrough from langchain_community.vectorstores import FAISS import libsbml +import re def analyze_model_species(sbml_file_path): @@ -108,8 +109,16 @@ def load_and_process_pdf(pdf_path): return vectorstore, documents -def extract_keywords_from_pdf(documents): - """Extract the top biomedical entity keywords from the PDF""" +def extract_keywords_from_pdf(documents, num_keywords=20): + """Extract the top N biomedical entity keywords from the PDF + + Args: + documents: List of documents to extract keywords from + num_keywords: Number of keywords to extract (default: 10) + + Returns: + List of keywords with standardized format (uses abbreviations, removes parentheses) + """ llm = ChatOpenAI(model="gpt-4o") # Combine all document content @@ -120,7 +129,7 @@ def extract_keywords_from_pdf(documents): # Create a prompt for keyword extraction focusing on biomedical entities prompt = PromptTemplate.from_template( """You are given a scientific document related to a systems biology model. - Extract exactly top thirty key biomedical entities that best represent the main focus of this document. + Extract exactly {num_keywords} key biomedical entities that best represent the main focus of this document. FOCUS ONLY ON: - Disease names (e.g., Alzheimer's disease, cancer, diabetes) @@ -131,20 +140,39 @@ def extract_keywords_from_pdf(documents): DO NOT INCLUDE general methodologies, modeling approaches, or broad fields of study. + IMPORTANT FORMATTING RULES: + 1. When an entity has both a full name and abbreviation, use ONLY the abbreviation (e.g., use "IL-6" instead of "Interleukin-6") + 2. Do not include any parentheses in your output + 3. Do not include the full name with the abbreviation (e.g., do not return "Interleukin-6 (IL-6)") + Format your response as a comma-separated list. Document: {text} - top thirty BIOMEDICAL ENTITY KEYWORDS:""" + {num_keywords} BIOMEDICAL ENTITY KEYWORDS:""" ) # Create and run the chain chain = prompt | llm | StrOutputParser() - keywords = chain.invoke({"text": full_text[:10000]}) # Use first 10000 chars if doc is very large + keywords = chain.invoke({"text": full_text[:15000], "num_keywords": num_keywords}) # Increased char limit to get more context # Process the result to get a clean list keyword_list = [k.strip() for k in keywords.split(',')] - return keyword_list[:20] # Ensure we get top keywords + + # Additional processing to standardize format + cleaned_keywords = [] + for keyword in keyword_list: + # Remove any remaining parenthetical content + cleaned = re.sub(r'\s*\([^)]*\)', '', keyword) + # Remove any special characters except hyphens and spaces + cleaned = re.sub(r'[^\w\s\-]', '', cleaned) + # Normalize whitespace + cleaned = re.sub(r'\s+', ' ', cleaned).strip() + if cleaned: # Only add non-empty strings + cleaned_keywords.append(cleaned) + + # Ensure we get exactly the requested number of keywords (if available) + return cleaned_keywords[:num_keywords] def parse_sbml_model(sbml_file_path): """Parse SBML model and extract species only, handling duplicate names""" diff --git a/notebook/species_backgrounds.csv b/notebook/species_backgrounds.csv index d6804df3..c1bf4ef6 100644 --- a/notebook/species_backgrounds.csv +++ b/notebook/species_backgrounds.csv @@ -1,22 +1,8 @@ id,name,original_name,compartment,background -mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species named 'IL6' in the provided context likely refers to the cytokine Interleukin-6, which plays a crucial role in the immune system. +mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"IL6, or Interleukin 6, is a cytokine that plays a significant role in the immune system. It is particularly important in the context of Crohn's disease, as it contributes to enhanced T-cell survival and apoptosis resistance in the lamina propria, along with increased chemokine secretion. IL-6 signaling occurs through two pathways: the classical pathway mediated by the membrane-bound IL-6 receptor (IL-6Rα) and the trans-signaling pathway mediated by the soluble IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of the gp130 coreceptor to form a receptor complex that initiates downstream signaling cascades. -### Biological Function: -- **Interleukin-6 (IL-6)** is a cytokine, a type of signaling molecule in the immune system, involved in inflammation and infection responses, as well as the regulation of metabolic, regenerative, and neural processes. +The active hexameric IL-6 receptor complex leads to the phosphorylation of gp130-bound Janus kinase (Jak) family proteins and subsequent activation of signal transducer and activator of transcription 3 (STAT3) via phosphorylation. This signaling is implicated in inflammation and autoimmunity processes, which are central to the pathology of Crohn's disease. -### Role in Pathways: -- IL-6 is essential in **immune regulation**, particularly in inflammatory responses. -- It signals via two main pathways: - - **Classical Pathway**: Involves the membrane-bound IL-6 receptor (IL-6Rα), where IL-6 binds to the IL-6Rα, and this complex recruits the membrane-bound co-receptor gp130, forming a heterotrimer, which subsequently dimerizes into an active hexameric complex. - - **Trans-Signaling Pathway**: Involves the soluble IL-6 receptor (sIL-6Rα), where a preformed IL-6/sIL-6Rα complex in the circulation interacts with gp130 on the cell surface, allowing cells that do not express the IL-6Rα on their surface to respond to IL-6. +Additionally, the model discussed in the provided context focuses on the pharmacokinetics and dynamics of anti–IL-6 and anti–IL-6Rα antibodies, such as tocilizumab, used in the treatment of autoimmune diseases like rheumatoid arthritis. These antibodies target the IL-6 pathways, particularly affecting how IL-6 signaling is modulated, and the model attempts to understand the therapeutic impact and dosing regimens of these biologics. -### Interactions with Other Molecules: -- IL-6 interacts with **IL-6Rα** (both membrane-bound and soluble) and the co-receptor **gp130**, leading to activation of intracellular signaling cascades, primarily involving the **Janus kinase (Jak) family** proteins and subsequent phosphorylation of **signal transducer and activator of transcription 3 (STAT3)**. -- Antibodies targeting IL-6, such as in therapeutics, can affect these interactions and pathways, influencing the immune response and highlighting their use in treatments for diseases like rheumatoid arthritis and potentially Crohn's disease. - -### Importance in the Biological System Being Modeled: -- In the context of **Crohn's Disease**, IL-6 is a significant player in exacerbating disease symptoms by promoting T-cell survival and resistance to apoptosis, thus contributing to chronic inflammation. -- IL-6 signaling increases chemokine secretion, further amplifying inflammatory responses. -- Its pathways are critical targets for therapeutic interventions aiming to modulate immune responses and alleviate disease symptoms. - -Overall, IL-6 is a multifunctional cytokine, pivotal in immune regulation, inflammation, and cellular signaling, making it a critical focus for therapeutic targeting in various inflammatory diseases." +Overall, IL6 is critical in immune regulation and is a key target for therapeutic intervention in diseases characterized by dysregulated immune responses." From 63125ff3f31d44e8c53492a0724e8794d4e35fc2 Mon Sep 17 00:00:00 2001 From: Inigo Date: Fri, 7 Mar 2025 12:10:11 +0000 Subject: [PATCH 08/14] More stuff on my side --- .../talk2knowledgegraphs/kg_test.ipynb | 12392 ---------------- .../species_backgrounds.csv | 655 + .../tutorial_primekg_subgraph.ipynb | 6 +- notebook/embeddings_and_evaluation.ipynb | 8407 +++++++++++ notebook/species_backgrounds.csv | 658 +- .../subgraph_generation.ipynb | 2225 +-- 6 files changed, 10946 insertions(+), 13397 deletions(-) delete mode 100644 docs/notebooks/talk2knowledgegraphs/kg_test.ipynb create mode 100644 docs/notebooks/talk2knowledgegraphs/species_backgrounds.csv create mode 100644 notebook/embeddings_and_evaluation.ipynb rename docs/notebooks/talk2knowledgegraphs/subgraph_generation_sheng+inigo.ipynb => notebook/subgraph_generation.ipynb (59%) diff --git a/docs/notebooks/talk2knowledgegraphs/kg_test.ipynb b/docs/notebooks/talk2knowledgegraphs/kg_test.ipynb deleted file mode 100644 index a0d7f764..00000000 --- a/docs/notebooks/talk2knowledgegraphs/kg_test.ipynb +++ /dev/null @@ -1,12392 +0,0 @@ -{ - "cells": [ - { - "cell_type": "code", - "execution_count": 1, - "id": "d351ee6b-d9da-493b-b072-1dc8380307f3", - "metadata": {}, - "outputs": [ - { - "name": "stderr", - "output_type": "stream", - "text": [ - "/home/oneai/miniconda3/envs/py311/lib/python3.11/site-packages/tqdm/auto.py:21: TqdmWarning: IProgress not found. Please update jupyter and ipywidgets. See https://ipywidgets.readthedocs.io/en/stable/user_install.html\n", - " from .autonotebook import tqdm as notebook_tqdm\n" - ] - } - ], - "source": [ - "# Import necessary libraries\n", - "import os\n", - "import numpy as np\n", - "import pandas as pd\n", - "import networkx as nx\n", - "import pickle\n", - "from tqdm import tqdm\n", - "from torch_geometric.utils import from_networkx\n", - "import sys\n", - "sys.path.append('../../..')\n", - "from aiagents4pharma.talk2knowledgegraphs.datasets.primekg import PrimeKG\n", - "from aiagents4pharma.talk2knowledgegraphs.datasets.starkqa_primekg import StarkQAPrimeKG\n", - "from aiagents4pharma.talk2knowledgegraphs.utils.embeddings.ollama import EmbeddingWithOllama\n", - "from aiagents4pharma.talk2knowledgegraphs.utils import kg_utils\n", - "\n", - "import matplotlib.pyplot as plt\n", - "\n", - "# # Set the logging level for httpx to WARNING to suppress INFO messages\n", - "import logging\n", - "logging.getLogger(\"httpx\").setLevel(logging.WARNING)" - ] - }, - { - "cell_type": "code", - "execution_count": 2, - "id": "f724e7f5-1dbf-45cb-a60d-f48180b7adab", - "metadata": {}, - "outputs": [], - "source": [ - "local_dir = '../../../aiagents4pharma/talk2knowledgegraphs/tests/files/primekg_ibd_pyg_graph.pkl'" - ] - }, - { - "cell_type": "code", - "execution_count": 3, - "id": "a6619d22-6e3e-4167-9231-acfd5a69eeaa", - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "Data(x=[3426, 768], edge_index=[2, 12752], edge_attr=[12752, 768], node_id=[3426], node_name=[3426], node_type=[3426], enriched_node=[3426], key=[12752], head_id=[12752], head_name=[12752], tail_id=[12752], tail_name=[12752], edge_type=[12752], enriched_edge=[12752])" - ] - }, - "execution_count": 3, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "with open(local_dir, 'rb') as file:\n", - " data = pickle.load(file)\n", - "\n", - "data" - ] - }, - { - "cell_type": "code", - "execution_count": 4, - "id": "d62c7c8d-760f-44d3-9c37-ddafbd45fd3e", - "metadata": {}, - "outputs": [], - "source": [ - "G = nx.Graph()\n", - "\n", - "# Add nodes to the graph\n", - "for i in range(len(data['node_id'])):\n", - " G.add_node(\n", - " data['node_id'][i],\n", - " name=data['node_name'][i],\n", - " type=data['node_type'][i],\n", - " enriched_node=data['enriched_node'][i],\n", - " features=data['x'][i].numpy(), # You can add the node features as well\n", - " )\n", - "\n", - "# Add edges to the graph\n", - "for i in range(data['edge_index'].shape[1]): # 12752 edges\n", - " head = data['head_id'][i]\n", - " tail = data['tail_id'][i]\n", - " G.add_edge(\n", - " head,\n", - " tail,\n", - " edge_attr=data['edge_attr'][i].numpy(),\n", - " edge_type=data['edge_type'][i],\n", - " enriched_edge=data['enriched_edge'][i]\n", - " )" - ] - }, - { - "cell_type": "code", - "execution_count": 5, - "id": "53dea1e5-24b8-4705-ac23-0ef1d6f7883e", - "metadata": {}, - "outputs": [ - { - "data": { - "image/png": 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", - "text/plain": [ - "
" - ] - }, - "metadata": {}, - "output_type": "display_data" - } - ], - "source": [ - "first_100_nodes = list(G.nodes)[:100]\n", - "\n", - "subgraph = G.subgraph(first_100_nodes)\n", - "\n", - "plt.figure(figsize=(5, 5))\n", - "nx.draw(subgraph, with_labels=True, node_size=50, font_size=8, node_color='skyblue')\n", - "plt.title(\"Subgraph with First 100 Nodes\")\n", - "plt.show()\n" - ] - }, - { - "cell_type": "markdown", - "id": "c3cc2316-c188-45fc-ad72-80e77fcb7396", - "metadata": {}, - "source": [ - "----------" - ] - }, - { - "cell_type": "markdown", - "id": "1e3c0056-0ab0-4551-a158-b2c809d76378", - "metadata": {}, - "source": [ - "### Bert model - transforming from text to tensor" - ] - }, - { - "cell_type": "code", - "execution_count": 6, - "id": "0273b3be-d420-4a2b-b1ca-de0a3e05e8e6", - "metadata": {}, - "outputs": [], - "source": [ - "from transformers import BertTokenizer, BertModel\n", - "from transformers import AutoTokenizer, AutoModel\n", - "import torch" - ] - }, - { - "cell_type": "code", - "execution_count": 7, - "id": "d9c7affa-2558-433d-a3b1-b5dcf31b7ccd", - "metadata": {}, - "outputs": [], - "source": [ - "tokenizer = BertTokenizer.from_pretrained('bert-base-uncased')\n", - "model = BertModel.from_pretrained('bert-base-uncased')\n", - "\n", - "def get_text_embedding(text):\n", - " inputs = tokenizer(text, return_tensors='pt', truncation=True, padding=True, max_length=256)\n", - " outputs = model(**inputs)\n", - " # Get the mean of the hidden states (contextual embeddings)\n", - " \n", - " return outputs.last_hidden_state.mean(dim=1).detach().numpy() # Shape: (1, hidden_size)\n", - "\n", - "# Example: Get embedding for a species description\n", - "text_description = \"STAT3 belongs to gene/protein category. The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2.\"\n", - "text_embedding = get_text_embedding(text_description)\n" - ] - }, - { - "cell_type": "markdown", - "id": "764bdd6c-1e62-4a42-b97d-d43644ba82d9", - "metadata": {}, - "source": [ - "### Graph behaviour" - ] - }, - { - "cell_type": "markdown", - "id": "b0e26fcb-9506-4c2e-9e9f-dfe14efa3f23", - "metadata": {}, - "source": [ - "We pass each enriched node text through the BERT model to obtain an embedding" - ] - }, - { - "cell_type": "code", - "execution_count": 8, - "id": "e6c0fe91-e158-4fb3-aa91-d96e54ec5f88", - "metadata": { - "scrolled": true - }, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "0 / 3426\n", - "1 / 3426\n", - "2 / 3426\n", - "3 / 3426\n", - "4 / 3426\n", - "5 / 3426\n", - "6 / 3426\n", - "7 / 3426\n", - "8 / 3426\n", - "9 / 3426\n", - "10 / 3426\n", - "11 / 3426\n", - "12 / 3426\n", - 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" # Optionally, invoke garbage collection after every `batch_size` nodes processed\n", - " if node_idx % batch_size == 0 and node_idx != 0:\n", - " gc.collect() # Force garbage collection to free memory\n" - ] - }, - { - "cell_type": "markdown", - "id": "750eb21d-f40c-413e-8982-6ce0ec41d21e", - "metadata": {}, - "source": [ - "### We add neighbor embeddings" - ] - }, - { - "cell_type": "code", - "execution_count": 9, - "id": "4c61048d-ca2e-407f-b72c-828852e7302f", - "metadata": { - "scrolled": true - }, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "0\n", - "1\n", - "2\n", - "3\n", - "4\n", - "5\n", - "6\n", - "7\n", - "8\n", - "9\n", - "10\n", - "11\n", - "12\n", - "13\n", - "14\n", - "15\n", - "16\n", - "17\n", - "18\n", - "19\n", - "20\n", - "21\n", - "22\n", - "23\n", - "24\n", - "25\n", - "26\n", - "27\n", - "28\n", - "29\n", - "30\n", - "31\n", - "32\n", - "33\n", - "34\n", - "35\n", - "36\n", - "37\n", - "38\n", - "39\n", - "40\n", - "41\n", - "42\n", - 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" # Find neighbors N hops away (for hops 1, 2, etc.)\n", - " nodes_n_hops_away = [\n", - " neighbor for neighbor, dist in nx.single_source_shortest_path_length(G, node_name).items() \n", - " if dist == prop_idx + 1 and neighbor not in seen_nodes\n", - " ]\n", - " \n", - " # Update the seen nodes with the current level's neighbors\n", - " seen_nodes.update(nodes_n_hops_away)\n", - " \n", - " # Add the embeddings for these neighbors, weighted by proportion\n", - " for neighbor_idx in nodes_n_hops_away:\n", - " neighbor_node = G.nodes[neighbor_idx]\n", - " embedding += neighbor_node['BERT_embedding'] * proportions[prop_idx]\n", - " weight += proportions[prop_idx] # Add the weight of the current hop level\n", - "\n", - " # Normalize the final embedding by the total weight\n", - " node['FINAL_embedding'] = embedding / weight\n", - " #print(f\"Final embedding for node {node_name}: {node['FINAL_embedding']}\")\n" - ] - }, - { - "cell_type": "code", - "execution_count": 10, - "id": "108662ac-0f82-44d3-9c0a-ac64072f5646", - 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" 4.10985041e+00, -3.19601965e+00, 4.29234457e+00,\n", - " -2.96037292e+00, -1.41816318e+00, -6.90810776e+00,\n", - " -1.77858877e+00, -6.97060156e+00, 2.49163747e+00,\n", - " 6.40245259e-01, 1.34561968e+00, -1.63573682e-01,\n", - " -8.01140219e-02, -8.43061328e-01, 2.00651050e+00,\n", - " -1.96246290e+00, -3.42135429e+00, 2.77661729e+00]], dtype=float32)" - ] - }, - "execution_count": 10, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "na = nodes_list[1]\n", - "G.nodes[na]['BERT_embedding']" - ] - }, - { - "cell_type": "markdown", - "id": "4d2003b5-52c4-4f18-a30e-54ee4a442a99", - "metadata": {}, - "source": [ - "### Obtain most similar embedding" - ] - }, - { - "cell_type": "code", - "execution_count": 11, - "id": "143fede2-c942-4eac-a544-277f88b20479", - "metadata": { - "scrolled": true - }, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "5.3094707\n", - "3.7479894\n", - "4.25238\n", - "4.854794\n", - "5.018378\n", - "5.0496874\n", - 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" \n", - " #cosine_sim = np.dot(curr_emb, text_embedding) / (np.linalg.norm(curr_emb) * np.linalg.norm(text_embedding))\n", - " linear_sim = np.linalg.norm(curr_emb - text_embedding)\n", - " print(linear_sim)\n", - " if ((best_node is None) | (linear_sim < best_sim)):\n", - " best_node = node_name\n", - " best_sim = linear_sim" - ] - }, - { - "cell_type": "code", - "execution_count": 12, - "id": "27bee18b-e76b-43f1-9bcd-7866ffc9d394", - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "'IL10RB_(179)'" - ] - }, - "execution_count": 12, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "best_node" - ] - }, - { - "cell_type": "code", - "execution_count": 13, - "id": "542c3bb4-4a1f-4f84-850f-ca690cd1c8ad", - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "3.7479894" - ] - }, - "execution_count": 13, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "best_sim" - ] - }, - { - "cell_type": "code", - "execution_count": 14, - "id": "fecc0f76-1116-400a-a021-99f493e30ced", - "metadata": { - "scrolled": true - }, - "outputs": [ - { - "data": { - "text/plain": [ - "{'name': 'IL10RB',\n", - " 'type': 'gene/protein',\n", - " 'enriched_node': 'IL10RB belongs to gene/protein category. The protein encoded by this gene belongs to the cytokine receptor family. It is an accessory chain essential for the active interleukin 10 receptor complex. Coexpression of this and IL10RA proteins has been shown to be required for IL10-induced signal transduction. This gene and three other interferon receptor genes, IFAR2, IFNAR1, and IFNGR2, form a class II cytokine receptor gene cluster located in a small region on chromosome 21. [provided by RefSeq, Jul 2008].',\n", - " 'features': array([ 2.47649457e-02, 2.27820016e-02, -1.69560522e-01, -3.35070789e-02,\n", - " 8.52039382e-02, -4.47765887e-02, 4.06866398e-04, 3.38708200e-02,\n", - " 8.85483692e-04, -5.48509024e-02, -2.48616599e-02, 4.08173949e-02,\n", - " 5.26165143e-02, -9.47317749e-04, 6.65599257e-02, -2.95930486e-02,\n", - " -2.54397616e-02, 1.05780065e-02, 2.82950737e-02, 3.88805866e-02,\n", - " -3.57877351e-02, -2.41180733e-02, 2.66018300e-03, 4.74014170e-02,\n", - " 1.24380529e-01, 8.75102133e-02, 2.64107957e-02, -5.74104190e-02,\n", - " -4.51339521e-02, -6.16167374e-02, 4.16413024e-02, -1.24433022e-02,\n", - " 2.79269870e-02, -5.66958301e-02, 1.06925778e-02, -2.90871635e-02,\n", - " 2.93817129e-02, -1.29560931e-02, -5.70652001e-02, 3.95376422e-02,\n", - " 3.77608836e-02, -4.29488271e-02, 3.73597853e-02, -1.16063925e-02,\n", - " 4.03282456e-02, 4.86438572e-02, 3.09612006e-02, 6.15862347e-02,\n", - " 7.20024034e-02, -1.01926383e-02, 2.76156757e-02, -6.31420538e-02,\n", - 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The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. This gene also plays a role in regulating host response to viral and bacterial infections. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. [provided by RefSeq, Aug 2020].',\n", - " 'features': array([ 0.04315694, 0.04914289, -0.16484766, -0.00853863, 0.06265302,\n", - " -0.01541665, 0.02753372, 0.03142512, 0.038947 , -0.05401486,\n", - " -0.03537597, 0.04720429, 0.08712805, -0.03483273, 0.02255078,\n", - " -0.01788178, -0.05623956, -0.0228414 , 0.00061129, 0.08702788,\n", - " -0.03903154, -0.05354989, -0.00051137, 0.02202799, 0.1298917 ,\n", - " 0.06630778, -0.02360412, -0.01152528, -0.01520275, -0.0095151 ,\n", - " 0.03934141, -0.00331436, -0.0031451 , -0.04750327, 0.02694312,\n", - " -0.05911469, 0.08366401, 0.00760372, -0.02688647, 0.00031389,\n", - " -0.0044422 , -0.0416383 , 0.01800342, -0.02480288, 0.00750974,\n", - " 0.01963029, -0.00587837, 0.010777 , 0.06374839, -0.08214433,\n", - " 0.01446381, -0.02693685, 0.01618203, -0.02410712, 0.07144384,\n", - " -0.00121614, -0.00579815, -0.04320944, 0.00903543, -0.03210413,\n", - " 0.06976824, 0.0696892 , -0.10718722, -0.0240883 , 0.08434569,\n", - " -0.04129338, 0.00040258, 0.07766017, -0.03395101, -0.02969847,\n", - 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" 3.70059848e-01, -2.38094870e-02, -1.51231825e-01,\n", - " -1.91220865e-01, -1.76654652e-01, -2.22343206e-01,\n", - " -3.19126189e-01, 4.69284058e-01, 3.71696591e-01,\n", - " -6.11030042e-01, -1.62205994e-02, 5.88009536e-01,\n", - " 4.41028446e-01, -1.04288245e-02, -2.55315900e-01,\n", - " -8.10149983e-02, 2.52229780e-01, 2.57740349e-01,\n", - " -2.83147991e-02, -5.48651367e-02, -6.95473999e-02,\n", - " -3.99503022e-01, 3.00514102e-01, -4.65655118e-01,\n", - " -2.51234304e-02, 7.41387457e-02, 4.72613245e-01,\n", - " 5.54493189e-01, -3.04996371e-01, 1.44094646e-01,\n", - " -3.31106186e-01, -1.04692966e-01, -6.80046499e-01,\n", - " -1.42271742e-01, -7.61844397e-01, 3.36764395e-01,\n", - " 5.06991409e-02, 1.67209953e-01, 4.09651883e-02,\n", - " 4.35570739e-02, -1.06503882e-01, 1.57247260e-01,\n", - " -3.07127148e-01, -3.02575976e-01, 2.61946321e-01]], dtype=float32)}" - ] - }, - "execution_count": 15, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "G.nodes['STAT3_(729)']" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "id": "4982e002-b541-4a12-b843-711f13ecfb58", - "metadata": {}, - "outputs": [], - "source": [] - } - ], - "metadata": { - "kernelspec": { - "display_name": "Python (myenv)", - "language": "python", - "name": "myenv" - }, - "language_info": { - "codemirror_mode": { - "name": "ipython", - "version": 3 - }, - "file_extension": ".py", - "mimetype": "text/x-python", - "name": "python", - "nbconvert_exporter": "python", - "pygments_lexer": "ipython3", - "version": "3.11.11" - } - }, - "nbformat": 4, - "nbformat_minor": 5 -} diff --git a/docs/notebooks/talk2knowledgegraphs/species_backgrounds.csv b/docs/notebooks/talk2knowledgegraphs/species_backgrounds.csv new file mode 100644 index 00000000..f9e0d87d --- /dev/null +++ b/docs/notebooks/talk2knowledgegraphs/species_backgrounds.csv @@ -0,0 +1,655 @@ +id,name,background +mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,"Based on the provided context, IL6 (interleukin-6) is a cytokine that plays a vital role in immune regulation, particularly in the context of inflammatory diseases like Crohn's disease. Here is a summary of its background information: + +1. **Biological Function:** + - IL6 is a critical mediator in the immune system, known for its involvement in inflammation and immune responses. + - It contributes to the survival of T-cells and resistance to apoptosis, especially in the lamina propria, a tissue region in the gut affected in Crohn’s disease. + +2. **Role in Pathways:** + - IL6 signaling occurs through two main pathways: + - The classical pathway involves a membrane-bound IL-6 receptor (IL-6Rα). + - The trans-signaling pathway involves a soluble IL-6 receptor (sIL-6Rα). + - These pathways lead to the formation of a complex that activates the phosphorylation of gp130-bound Janus kinase (Jak) family proteins, followed by the phosphorylation of STAT3 (signal transducer and activator of transcription 3). + +3. **Interactions with Other Molecules:** + - IL6 forms a dimer/complex with IL-6Rα or sIL-6Rα, which then associates with a gp130 coreceptor to form a hexameric receptor complex. + - This complex initiates downstream signaling critical for immune responses. + - There are interactions with therapeutic antibodies, such as those targeting IL-6 or IL-6Rα, which can modulate its activity, an approach used in diseases like rheumatoid arthritis. + +4. **Importance in the Biological System:** + - In diseases like Crohn’s disease, IL6-mediated signaling is significant due to its role in promoting inflammatory responses and affecting chemokine secretion, leading to prolonged inflammation. + - Targeting IL6 pathways is a therapeutic strategy used to control excessive inflammation and treat autoimmune diseases. + +In conclusion, IL6 is a highly influential cytokine in immune regulation, particularly in inflammatory and autoimmune conditions, where it plays roles in cell survival, signaling pathways, and interactions with therapeutic agents." +mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130,"Based on the provided context, the species 'sgp130' appears to be a component involved in the signaling pathways mediated by interleukin-6 (IL-6), specifically in the context of IL-6 trans-signaling. Here is a summary of relevant information about sgp130 based on the provided documents: + +1. **Biological Function:** + - sgp130 is a soluble form of gp130, which is involved in signal transduction for IL-6 and other cytokines. + - It is involved in inhibiting IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex. This indicates that sgp130 can modulate inflammatory responses mediated by IL-6. + +2. **Role in Pathways:** + - sgp130 specifically inhibits IL-6 trans-signaling, which typically occurs when the IL-6/sIL-6Rα complex interacts with membrane-bound gp130 on target cells. By binding with the complex, sgp130 prevents this interaction, potentially reducing pathological signaling associated with diseases such as Crohn’s disease. + +3. **Interactions with Other Molecules:** + - sgp130 interacts with the complex formed by IL-6 and its soluble receptor, sIL-6Rα. This interaction is a key mechanism by which sgp130 exerts its inhibitory effects on IL-6 mediated signaling. + +4. **Importance in the Biological System:** + - The context indicates that sgp130 is present in high baseline concentrations compared to IL-6, suggesting its physiological role as a moderator of IL-6 activity. + - The high baseline level of sgp130 and its excess relative to IL-6 suggest that it can effectively suppress IL-6 trans-signaling under normal conditions. + - The model described suggests that despite its high concentration, sgp130 has a minimal effect on system dynamics unless present in very high doses. This may reflect the physiological buffering role it plays to protect against excessive IL-6 activity. + - However, sgp130-based therapies may not be as effective as treatments targeting IL-6 or sIL-6Rα directly, due to its relatively lower influence on the system dynamics in terms of biomarker changes. + +In summary, sgp130 is important as a regulatory molecule in cytokine signaling pathways, particularly those involving IL-6, with potential therapeutic implications in modulating inflammatory and immune responses." +mw810ff751_fa4e_4143_bd50_169b3e325e1e,sR_IL6_sgp130,"Based on the provided context, 'sR_IL6_sgp130' is likely a component that is involved in the IL-6 signaling pathway, which is known to play a crucial role in inflammatory responses and immune regulation. The context refers to sgp130, which is described as a fusion protein that combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein, named sgp130Fc, is used to inhibit IL-6 trans-signaling. + +### Biological Function: +sR_IL6_sgp130 is not directly mentioned in the text, but based on similar components, it likely functions to modulate the IL-6 signaling pathway. In particular, sR_IL6_sgp130 might interact with the IL-6/sIL-6R complex, playing a role in inhibiting the trans-signaling process. + +### Role in Pathways: +The IL-6 signaling pathway is addressed in the context of both Classical and Trans signaling. While classical signaling involves IL-6 binding to membrane-bound IL-6 receptor (IL-6R) and gp130, trans-signaling involves IL-6 binding to soluble IL-6R (sIL-6R), allowing it to interact with gp130 on cells that do not express IL-6R. sR_IL6_sgp130 would participate in the inhibition of trans-signaling by binding to the IL-6/sIL-6R complex. + +### Interactions with Other Molecules: +In the context of the modeling study, sgp130Fc is assumed to bind the IL-6/sIL-6R complex with similar affinity to natural sgp130. This suggests that sR_IL6_sgp130 might also interact with IL-6, sIL-6R, and potentially compete or interfere with their binding to gp130, effectively inhibiting signaling pathways downstream. + +### Importance in the Biological System: +The presence of sgp130 in excess compared to free IL-6 indicates its potential role as a regulatory buffer in the signaling pathway. The study suggests that the system's sensitivity to changes in sgp130 levels is low unless there are significant deviations from baseline levels. This implies that while sgp130 (and by extrapolation, sR_IL6_sgp130) is important, its effects on the system dynamics are subtle unless present in large amounts, reaffirming its regulatory role. + +In summary, sR_IL6_sgp130 is inferred to be a critical modulator in the IL-6 signaling pathway, particularly involved in regulating the trans-signaling pathway by interacting with the IL-6/sIL-6R complex and potentially influencing inflammatory and immune responses." +mw114aa90f_5f5b_4fe8_9406_361c8489b6a1,CRP,"Based on the provided context, CRP, or C-reactive protein, is a biomarker commonly used to assess inflammation in the body. Here is a summary of relevant background information regarding CRP: + +1. **Biological Function**: CRP is a protein found in the blood, produced by the liver, and its levels increase in response to inflammation. It is part of the body's acute phase response to inflammation, infection, or injury. + +2. **Role in Pathways**: CRP is a key inflammatory marker often assessed in clinical settings to evaluate inflammation levels. It is used to monitor diseases like Crohn's disease, where inflammation is a characteristic feature. The context suggests its levels are affected by treatments targeting IL-6 signaling, which is a pathway involved in immune responses and inflammation. + +3. **Interactions with Other Molecules**: The context highlights interactions between CRP and interleukin-6 (IL-6) signaling pathways. IL-6 is a cytokine that activates the acute phase response, leading to increased CRP production. Treatments that target IL-6 or its receptor (IL-6Rα) can lead to a decrease in CRP levels by mitigating inflammation. + +4. **Importance in the Biological System Being Modeled**: CRP serves as a significant marker for inflammation in the model described. The model evaluates the effectiveness of different treatment strategies for managing inflammation, particularly in conditions like Crohn's disease, by measuring changes in CRP levels. The modulation of CRP through therapeutic interventions indicates the model's ability to simulate the inflammatory response to drug treatments. + +Overall, CRP is critical for monitoring and understanding inflammatory processes and the effectiveness of interventions in inflammatory diseases." +mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc,sR,"From the provided documents, there is no specific mention of a species named 'sR' with the ID mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc. However, there are references to molecules and components related to the IL-6 signaling pathway, such as sIL-6R (soluble IL-6 receptor) and sgp130, which are involved in IL-6 mediated signaling. + +### Inferred Background Information about 'sR': + +1. **Biological Function:** + - Based on similar naming conventions, 'sR' could potentially refer to a soluble receptor or a molecule that has a regulatory or auxiliary role in signaling pathways, possibly related to cytokine signaling like IL-6. + +2. **Role in Pathways:** + - If 'sR' is associated with processes similar to sIL-6R, it may be involved in modulating cytokine actions. Soluble receptors like sIL-6R often bind cytokines in the bloodstream, influencing their bioavailability and activity. + +3. **Interactions with Other Molecules:** + - Soluble receptors typically interact with ligands or other receptor components (e.g., cytokines such as IL-6). They may act as either inhibitors by sequestering the ligand or enhancers by stabilizing receptor complexes. + - Related interactions could involve complex formation with cytokine molecules and possibly other receptors such as gp130. + +4. **Importance in the Biological System Being Modeled:** + - In the context of the IL-6 signaling described, 'sR' may play a role in modulating inflammatory responses or other gene expression pathways through its interaction with signaling molecules. + - It might be significant in balancing the dynamics of cytokine signaling, similar to how sgp130 is described as having minimal immediate impacts unless present in vastly altered concentrations. + +Since there is no explicit information on 'sR', the above inferences are drawn from typical functions and roles of soluble receptors in cytokine signaling pathways as exemplified by the mentioned components like sIL-6R." +mw03db56ac_8dc6_4931_ae82_fef706d2ee3d,sR_IL6,"Based on the provided context and general knowledge about similar biological components, the species ""sR_IL6"" appears to refer to the soluble receptor component related to the cytokine Interleukin-6 (IL-6). Below is a summary of relevant background information: + +1. **Biological Function**: + - sR_IL6, likely reflecting ""soluble IL-6 receptor"" (sIL-6R), is a part of the IL-6 signaling pathway. This soluble receptor can bind to IL-6, allowing it to interact with gp130, a signal-transducing receptor component, and mediate downstream signaling. + +2. **Role in Pathways**: + - IL-6 can signal through classical and trans-signaling pathways. The classical pathway involves the membrane-bound IL-6 receptor, while the trans-signaling pathway involves the soluble IL-6 receptor (sIL-6R). In the latter, sR_IL6 binds to IL-6, forming a complex that can interact with membrane-bound gp130 to initiate intracellular signaling cascades. + +3. **Interactions with Other Molecules**: + - sR_IL6 forms a complex with IL-6, known as the IL-6/sIL-6R complex. This complex can be sequestered by another protein called sgp130, which negatively regulates IL-6 signaling by preventing it from interacting with cell surface gp130. + - The interaction between IL-6/sR_IL6 and gp130 leads to the activation of the Jak/STAT3 signaling pathway, which is pivotal for mediating immune and inflammatory responses. + +4. **Importance in the Biological System**: + - The soluble receptor sR_IL6 is important in expanding the range of cells that can respond to IL-6, as not all cells express the membrane-bound IL-6 receptor. Through trans-signaling, it facilitates cellular responses in a broader repertoire of cell types, including those implicated in inflammation and immune responses. + - In the context of the multiscale model outlined in the document, sR_IL6 and its interactions are crucial in understanding mechanisms underlying diseases such as Crohn's disease and in evaluating therapeutic interventions targeting IL-6 signaling pathways. + +In summary, sR_IL6 plays a significant role in mediating IL-6-related signaling pathways, influencing immune regulation and inflammation, and is a critical component in the computational modeling of related diseases." +mwf345ed7a_0622_403c_b816_c8749a2c9ded,Ab,"The context provided from the documents appears to be focused on a biological or pharmacological study, particularly related to the immune response involving interleukin pathways and potentially antibodies. However, there is no direct information or explicit mention of the species or molecule named 'Ab' with the ID provided. + +Based on the typical use of ""Ab"" in biological contexts, especially when mentioned alongside dose response and serum concentrations, it likely refers to an antibody. The context involves interactions within the IL-6 signaling pathway, common in studies involving inflammatory diseases such as Crohn’s disease (CD), and it details the effects of targeting interleukin-6 (IL-6), its receptor (IL-6Rα), and their complex. + +Given this information, 'Ab' could refer to: + +1. **Biological Function**: 'Ab' functions as an antibody, possibly designed to bind to specific antigens like IL-6 or IL-6Rα, potentially modulating immune responses by inhibiting these targets to reduce inflammation or related symptoms. + +2. **Role in Pathways**: It plays a role in the IL-6 signaling pathway, likely targeting either IL-6, IL-6Rα, or their complex, which is crucial in mediating inflammatory responses. + +3. **Interactions with Other Molecules**: 'Ab' would interact with IL-6, IL-6Rα, and possibly the IL-6/sIL-6Rα complex. This interaction aims to reduce the signaling through the IL-6 pathway, which is implicated in inflammatory processes. + +4. **Importance in the Biological System Being Modeled**: In the context of this study, 'Ab' is an important therapeutic agent intended to suppress inflammatory markers such as C-reactive protein (CRP), as suppression of CRP would indicate reduced inflammation, which is crucial in diseases like inflammatory bowel diseases. + +Overall, while explicit information on 'Ab' is not provided, it can be inferred that 'Ab' is an antibody used to intervene in inflammatory signaling pathways by targeting components of the IL-6 signaling system." +mw1da111f2_a036_4392_8512_015005bdcbb7,Ab_sR,"The context provided does not contain specific information about the species named 'Ab_sR' (ID: mw1da111f2_a036_4392_8512_015005bdcbb7). However, we can infer certain aspects based on the context and general biological knowledge related to similar components. + +In the context given, there are discussions around IL-6 (Interleukin-6), sIL-6R (soluble IL-6 receptor), and their interactions. These are critical components of the IL-6 signaling pathway, which is significant in the regulation of immune responses, inflammation, and hematopoiesis. Particularly, the IL-6/sIL-6R complex is involved in the trans-signaling pathway, affecting various biological processes, such as acute-phase protein production in the liver (e.g., CRP - C-reactive protein) and potentially impacting inflammation and immune response regulation. + +Given this context, if 'Ab_sR' is presumed to be a molecule or species related to these pathways, it might play a role in interacting with IL-6 or its receptor components, such as sIL-6R, thereby influencing the pathway's function. If 'Ab_sR' is akin to an antibody, as suggested by the prefix ""Ab,"" it might be involved in modulating the IL-6 signaling through binding to IL-6, sIL-6R, or the IL-6/sIL-6R complex, potentially affecting immune signaling and inflammation. + +If 'Ab_sR' has an inhibitory function similar to that of an antibody targeting IL-6 or sIL-6R, it could contribute to downregulating excessive inflammatory responses, thus playing a protective role in conditions characterized by inflammation, like autoimmune diseases or chronic inflammatory states. + +In summary, without explicit details, 'Ab_sR' might be theorized to interact within the IL-6 signaling pathway, potentially moderating its activity and influencing broader biological functions related to inflammation and immune response regulation." +mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac,Ab_sR_IL6,"From the context provided, there is no direct mention of a biological species or molecule named 'Ab_sR_IL6'. However, I can infer what it might be based on the context and general understanding of similar biological components. + +Given the provided context, which involves IL-6 (Interleukin-6) and sIL-6R (soluble Interleukin-6 receptor), it is likely that 'Ab_sR_IL6' refers to an antibody directed against a complex involving these molecules. Here’s a possible breakdown of what 'Ab_sR_IL6' might represent based on the context: + +1. **Biological Function:** + - If 'Ab_sR_IL6' stands for an antibody targeting the soluble IL-6 receptor (sIL-6R) or the IL-6/sIL-6R complex, its primary biological function would be to inhibit the interaction of IL-6 with its receptor. This can prevent downstream signaling pathways that are activated by IL-6 binding, which are known to play roles in inflammatory and immune responses. + +2. **Role in Pathways:** + - IL-6 is involved in the JAK/STAT signaling pathway, leading to the activation of STAT3 and transcription of specific genes, including ones involved in inflammation. The antibody would act to disrupt this signaling pathway by preventing IL-6 from binding to the sIL-6R and further associating with the membrane-bound IL-6 receptor (IL-6R) and gp130, a signal transducer molecule. + +3. **Interactions with Other Molecules:** + - The 'Ab_sR_IL6' likely interacts with sIL-6R or the IL-6/sIL-6R complex to form a binding complex that prohibits IL-6-related signaling cascades. + - This interaction would affect the circulation of IL-6 and sIL-6R, and consequently, the levels of C-reactive protein (CRP) in systems such as the liver, as indicated by the discussion around CRP suppression. + +4. **Importance in the Biological System Being Modeled:** + - In the context of immune regulation, particularly relating to conditions like Crohn’s disease or rheumatoid arthritis, inhibiting IL-6 signaling through the action of the antibody could provide therapeutic benefits by reducing inflammation. + - The model suggests that targeting both IL-6 and IL-6/sIL-6R (potentially by an antibody like 'Ab_sR_IL6') might yield enhanced therapeutic benefits compared to targeting IL-6 alone. + +This inference leverages general knowledge about the IL-6 pathway and common antibody strategies in therapeutic interventions." +CRP_Suppression___,CRP Suppression (%),"Based on the context provided, ""CRP Suppression (%)"" appears to be a measurement or output rather than a biological species or molecule. It is related to the suppression or reduction of serum C-reactive protein (CRP) levels, which can be tracked as a percentage decrease from baseline levels. Here is the inferred background information: + +1. **Biological Function**: CRP is a protein produced by the liver in response to inflammation. It is a common marker used in clinical settings to assess acute inflammation and is part of the immune response. + +2. **Role in Pathways**: CRP is part of the inflammatory response pathway. It is typically upregulated in response to pro-inflammatory cytokines such as Interleukin-6 (IL-6). The context suggests that anti-IL-6 or anti-IL-6 receptor (IL-6R) treatments are being used to modulate CRP levels by reducing inflammation. + +3. **Interactions with Other Molecules**: In the context of anti-IL-6 and anti-IL-6R treatments, CRP levels are affected by these interventions, which target the IL-6 signaling pathway. The suppression of CRP is used as an indicator of the effectiveness of these treatments, implying that IL-6 and its receptor play significant roles in the regulation of CRP levels. + +4. **Importance in the Biological System**: The reduction in serum CRP levels, reflected as ""CRP Suppression (%)"", is used as a biomarker to assess the efficacy of treatments targeting IL-6 signaling. This makes CRP suppression a crucial readout in models studying inflammation and therapeutic interventions aimed at reducing inflammation. + +Therefore, while ""CRP Suppression (%)"" is not a biological species or molecule, it serves as a quantitative measure of the effectiveness of interventions targeting inflammation, specifically through the IL-6 pathway. The context indicates its use in evaluating the impact of various anti-inflammatory strategies." +CRP____of_baseline,CRP (% of baseline),"Based on the provided context and general knowledge, here is the background information about ""CRP (% of baseline)"": + +1. **Biological Function**: + - CRP stands for C-reactive protein, which is a substance produced by the liver in response to inflammation. It is a well-known biomarker for inflammation and can indicate the presence of inflammatory diseases or other conditions. + +2. **Role in Pathways**: + - CRP is involved in the immune system's response to inflammation. It functions by binding to lysophosphatidylcholine on the surface of dead or dying cells and some types of bacteria. This binding activates the complement system via C1q, promoting phagocytosis by macrophages, which is a key component of the immune response to infection or injury. + +3. **Interactions with Other Molecules**: + - CRP interacts with other molecules within the immune system, such as complement proteins. In the context of the provided documents, CRP levels are used as an indicator of inflammation reduction in response to anti-IL-6Rα therapy. CRP levels decrease when the therapy is effective, signaling reduced inflammation. + +4. **Importance in the Biological System Being Modeled**: + - In the context of the provided documents, CRP (% of baseline) is a crucial measure used to evaluate the efficacy of a treatment involving anti–IL-6Rα (tocilizumab) antibodies. Tocilizumab is used to treat immune-mediated conditions by blocking the interleukin-6 receptor (IL-6Rα), thereby reducing inflammation. Monitoring CRP levels over time allows researchers to confirm the treatment's impact on systemic inflammation. + +The term ""CRP (% of baseline)"" refers to the proportion of CRP levels at any given time point compared to the initial baseline level before treatment commenced. This percentage allows researchers to assess changes in CRP concentration as a direct result of therapeutic interventions, providing insights into how effectively the treatment controls inflammation." +mw80848184_e2dd_47ce_86d7_7a21479342bd,gp130,"Gp130 is an important protein involved in the cytokine signaling pathway, particularly in relation to interleukin-6 (IL-6) signaling. It acts as a signal transducer for the IL-6 family of cytokines and plays a critical role in the assembly and function of cytokine receptor complexes. Specifically, gp130 serves as a common signal transducing subunit for the IL-6 receptor complex, which includes the IL-6 receptor alpha (IL-6Rα) and the IL-6 cytokine itself. + +### Biological Function: +- **Signal Transduction**: Gp130 participates in transmitting signals from the IL-6/IL-6Rα complex inside the cell, resulting in various biological responses. It forms a hexameric complex with IL-6 and its receptor, which is crucial for initiating downstream signaling pathways. +- **Regulator Role**: Soluble gp130 (sgp130) acts as a natural inhibitor of IL-6 trans-signaling. It binds to the IL-6/sIL-6Rα complex, preventing its interaction with membrane-bound gp130, thus modulating the activity of IL-6. + +### Role in Pathways: +- **IL-6 Pathway**: Gp130 is fundamental in the IL-6 signal transduction pathway. It is involved in the initiation of cascades like the JAK/STAT pathway, which is important for gene expression and immune response regulation. +- **Inflammatory Response**: Through its interaction with IL-6, gp130 is implicated in the inflammatory response and has been linked to diseases such as Crohn's disease. + +### Interactions with Other Molecules: +- **Complex Formation**: Gp130 interacts with IL-6 and soluble IL-6Rα to form a signaling complex. This interaction is necessary for the proper signal transduction and is the target for various therapeutic interventions. +- **Therapeutic Applications**: Fusion proteins like sgp130Fc are designed to inhibit IL-6 trans-signaling by binding the IL-6/sIL-6Rα complex, which is being explored for therapeutic use in inflammatory diseases like Crohn’s. + +### Importance in Biological Systems: +- **Regulatory Mechanism**: Gp130 serves as a key regulatory mechanism in cytokine signaling, influencing immune system activity and inflammation. +- **Disease Targeting**: Because of its central role in cytokine signaling, particularly in inflammatory pathways, gp130 and its soluble form are subjects of therapeutic interest, aiming to manage chronic inflammatory conditions. + +In summary, gp130 is a critical component in cytokine receptor signaling, primarily involved in IL-6-related pathways, playing a significant role in immune responses and being a potential point of interference for therapeutic strategies in inflammatory diseases." +mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a,R_IL6_gp130,"The species named 'R_IL6_gp130', provided with the ID mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a, seems to relate to components involved in the interleukin-6 (IL-6) signaling pathway, specifically centered around the gp130 protein. Although the context provided does not explicitly describe 'R_IL6_gp130', we can infer its characteristics based on similar biological components related to gp130 in IL-6 signaling. + +### Biological Function and Role in Pathways +- **gp130 (Glycoprotein 130)**: Serves as a signal-transducing receptor component shared by many cytokine receptors. It plays a central role in the IL-6 family cytokine signaling mechanisms. +- **IL-6 Signaling**: The molecule gp130 is integral to both classical and trans-signaling pathways of IL-6. The classical pathway involves the membrane-bound IL-6 receptor (IL-6R) and is primarily active in immune cells. Trans-signaling occurs via a soluble form of the IL-6 receptor (sIL-6R) and is more widely active, affecting cells that do not have the IL-6 receptor. + +### Interactions with Other Molecules +- **IL-6/JAK/STAT Pathway**: The gp130 acts as the signal transducer for IL-6-type cytokine receptors, leading to activation of the JAK/STAT signaling cascade, which is crucial for immune responses and inflammation. +- **Soluble gp130 (sgp130)**: This can act as a natural inhibitor for the IL-6/sIL-6R complex, limiting the effects of IL-6 trans-signaling. + +### Importance in Biological Systems +- **Inflammation and Immune Response**: The IL-6/gp130 pathway is significant in the regulation of inflammatory responses, relevant in various diseases such as Crohn's disease, as mentioned in the context. +- **Therapeutic Implications**: Variants or derivatives like sgp130Fc, which can inhibit IL-6 trans-signaling, are under study as therapeutic options for inflammatory diseases. + +In summary, while specific data about 'R_IL6_gp130' is not explicitly detailed in the context, by contextual association, it likely refers to a key player within the IL-6 signaling pathway, particularly involving gp130 in modulating immune and inflammatory processes through its interactions with IL-6 and its receptors." +mw4638f126_8cb8_4021_ab41_6ae195743ba0,sR_IL6,"The species referred to as 'sR_IL6' in the provided context is likely a soluble receptor related to the interleukin-6 (IL-6) signaling pathway. However, the context primarily references sIL-6R (soluble IL-6 receptor), which plays a prominent role in IL-6 signaling. + +Here is a summary of the background information and inferred roles of 'sR_IL6', based on the context and general knowledge of similar molecules: + +1. **Biological Function**: sIL-6R, which 'sR_IL6' appears to be closely related to, acts as a soluble form of the membrane-bound IL-6 receptor. It binds to IL-6 and can participate in inducing cellular responses, even in cells that do not express the membrane-bound receptor (classical signaling). + +2. **Role in Pathways**: sIL-6R is involved in IL-6 trans-signaling. In this process, the IL-6:sIL-6R complex can interact with the signaling receptor gp130 on cell surfaces, initiating signal transduction inside these cells. This pathway is crucial for modulating inflammatory responses and is distinct from classical IL-6 signaling that involves membrane-bound IL-6R. + +3. **Interactions with Other Molecules**: sIL-6R interacts with IL-6 to form the IL-6:sIL-6R complex. This complex can be sequestered by sgp130, another soluble receptor, which regulates its availability and, thus, the extent of trans-signaling. + +4. **Importance in the Biological System**: In the context of the immune system, especially in diseases like Crohn's Disease, the IL-6:sIL-6R complex is critical due to its potent regulatory effects on inflammation. Targeting this complex can alter the disease course by modulating immune responses, highlighting its importance in therapeutic strategies. + +Overall, sR_IL6 (assuming it is similar to sIL-6R) is a crucial component of the IL-6 signaling system, facilitating interactions that expand the range of cells responsive to IL-6, thereby playing a significant role in immune regulation and inflammation." +mw10315fa3_6f13_4618_bda8_a8694bd3c374,R,"Based on the provided context, the document discusses interleukin-6 receptor (IL-6R) and related biological components. Although the species 'R' with the ID 'mw10315fa3_6f13_4618_bda8_a8694bd3c374' is not explicitly mentioned, we can infer its context within the study. + +The document describes the role of soluble interleukin-6 receptor (sIL-6R) and the targeting of IL-6Rα by antibodies, suggesting that 'R' could be connected to IL-6R, possibly a subtype or variant involved in the pathway under study. The general biological functions and roles related to IL-6R could include: + +1. **Biological Function**: IL-6R is a part of the signaling pathway for interleukin-6 (IL-6), a cytokine involved in immune responses, inflammation, and hematopoiesis. + +2. **Role in Pathways**: IL-6R is essential for the classical IL-6 signaling pathway, which involves the dimerization of IL-6/IL-6R complex with gp130, activating JAK/STAT signaling that leads to gene transcription. + +3. **Interactions with Other Molecules**: IL-6R interacts with IL-6 to form a complex that associates with gp130. It can exist in a soluble form (sIL-6R), which allows IL-6 signaling in cells lacking the membrane-bound receptor, extending the cytokine's effects. + +4. **Importance in Biological Systems**: IL-6R is crucial in moderating immune responses and inflammation. It is a therapeutic target in inflammatory diseases, as seen in treatments involving anti-IL-6R antibodies (e.g., tocilizumab) to reduce inflammatory markers like C-reactive protein (CRP). + +Due to the lack of specific mention of 'R,' it might represent a molecule involved in the broader IL-6/IL-6R signaling pathway being studied, potentially playing a similar role in inflammation and immune regulation." +mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1,IL6,"IL-6 (Interleukin-6) is a cytokine, a type of signaling molecule involved in immune regulation. It plays a significant role in the body's inflammatory response and is implicated in various diseases, including Crohn’s disease and rheumatoid arthritis. In Crohn's disease, IL-6 contributes to enhanced T-cell survival and resistance to apoptosis in the lamina propria, along with elevated chemokine secretion. This suggests a critical role in promoting inflammation and immune dysregulation associated with the disease. + +IL-6 signaling can occur through two main pathways: + +1. **Classical Signaling Pathway**: This occurs via the membrane-bound IL-6 receptor (IL-6Rα). In this pathway, IL-6 binds to IL-6Rα, and the complex recruits a membrane-bound co-receptor, gp130, forming a heterotrimer that subsequently dimerizes to create an active hexameric IL-6 receptor complex. This complex initiates the phosphorylation of gp130-bound Janus kinase (Jak) family proteins and leads to the phosphorylation of signal transducer and activator of transcription 3 (STAT3). + +2. **Trans-Signaling Pathway**: This involves the soluble IL-6 receptor (sIL-6Rα) and allows IL-6 signaling to occur even in cells that do not express IL-6Rα. The IL-6/sIL-6Rα complex can bind to gp130 on various cell types, activating similar downstream signaling pathways as the classical pathway. Trans-signaling is thought to be particularly significant in disease contexts, like Crohn’s disease, where it can exacerbate inflammation. + +IL-6 interacts with other molecules such as anti-IL-6 and anti-IL-6Rα antibodies. These interactions are crucial in therapeutic contexts, such as using tocilizumab, an anti-IL-6Rα antibody, in treating rheumatoid arthritis. Tocilizumab has been observed to have nonlinear clearance, consistent with its interaction dynamics with IL-6Rα, validating certain modeling approaches. + +Overall, IL-6 is an essential player in immune responses and inflammation, making it a critical target in therapies designed to modulate immune responses in various inflammatory diseases." +mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83,R_IL6,"The context provided from the document does not directly mention a species or molecule explicitly named 'R_IL6' with the specific ID provided. However, we can infer potential information about 'R_IL6' by examining similar components within the context of IL-6 signaling and receptor interactions as mentioned in the document. + +### Biological Function: +- **R_IL6** is likely to be some variant or receptor related to interleukin-6 (IL-6). IL-6 is a cytokine involved in inflammatory and immune responses. Receptors related to IL-6, such as IL-6 receptors, mediate its signaling and subsequent biological effects. + +### Role in Pathways: +- **IL-6 signaling** involves complex pathways where IL-6 binds to its receptor (IL-6R), which can exist in both membrane-bound and soluble forms. This interaction often leads to the activation of the JAK/STAT signaling pathway, resulting in the phosphorylation of STAT3 (pSTAT3) and the transcription of genes involved in inflammation, such as SOCS and CRP (C-reactive protein). + +### Interactions with Other Molecules: +- **IL-6 interacts** with its receptor (IL-6R), either in a classical membrane-bound form or in a form that involves soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130), facilitating signal transduction. This signaling can be modulated by molecules like anti-IL-6 or anti-IL-6R antibodies, which are studied for their effects in treating conditions like rheumatoid arthritis. + +### Importance in Biological Systems: +- **The IL-6/IL-6R system** plays a significant role in immune regulation. It is involved in acute phase reactions, hematopoiesis, immune responses, and inflammation. It is particularly important in disease contexts such as Crohn's Disease and rheumatoid arthritis, where dysregulation of its signaling pathway can lead to pathological outcomes. + +Given these functions and interactions, it is reasonable to infer that 'R_IL6' is an essential component within the IL-6 signaling pathway, potentially representing a receptor or regulatory element of the pathway, playing a pivotal role in mediating immune responses and inflammation in the biological system being modeled." +mw0eb6c959_d408_45a0_a450_928b8c5876bb,Ractive,"The provided context does not specifically mention the species 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb). Therefore, based on the general content of the documents, which discuss immune regulation, particularly involving IL-6 in conditions like Crohn’s Disease and rheumatoid arthritis, I can infer some potential roles for a species hypothetically named 'Ractive' within this context. + +1. **Biological Function**: Given the context focuses on immune regulation mediated by the cytokine IL-6, 'Ractive' could be speculated to play a role as a regulatory molecule or modulator within immune signaling pathways, possibly interacting with cytokines or receptors involved in inflammatory responses. + +2. **Role in Pathways**: It might be involved in pathways related to cytokine signaling, particularly influencing the IL-6 pathway or its interaction with the soluble IL-6 receptor (sIL-6Rα), given the emphasis in the document on these components and their therapeutic targeting. + +3. **Interactions with Other Molecules**: 'Ractive' could potentially interact with IL-6, its receptor IL-6Rα, or the IL-6/sIL-6Rα complex, affecting their activity, stability, or clearance in the system, similar to how antibodies like tocilizumab are described to interact with these components in the context provided. + +4. **Importance in the Biological System**: If 'Ractive' were involved in modulating IL-6 activity, it could be crucial in maintaining or restoring immune balance, particularly in pathological conditions like Crohn’s disease where IL-6 plays a significant role in the disease mechanism. + +This speculative function aligns with the themes observed in the documents, which focus on the modulation of cytokine activity and therapeutic interventions in inflammatory diseases." +mw42054cd7_17af_46da_970c_7f99151906ad,STAT3,"STAT3, or Signal Transducer and Activator of Transcription 3, is a transcription factor that plays a crucial role in cellular signaling pathways. It is known for its involvement in mediating the effects of cytokines and growth factors, particularly the signaling of interleukin-6 (IL-6). Here's a summary of the relevant aspects of STAT3 based on the provided context and general knowledge: + +1. **Biological Function**: + - STAT3 is activated through phosphorylation, typically following the engagement of cytokine receptors such as those for IL-6. Once phosphorylated, pSTAT3 dimerizes and translocates into the nucleus, where it functions as a transcription factor to regulate gene expression. + +2. **Role in Pathways**: + - STAT3 is a core component of the JAK-STAT signaling pathway. In particular, it plays a significant role in the signaling events triggered by IL-6. This cytokine binds to its receptor, IL-6Rα, and utilizes the coreceptor gp130. The activation process results in the phosphorylation of STAT3, which then facilitates the transcription of target genes involved in various physiological processes. + +3. **Interactions with Other Molecules**: + - STAT3 interacts with other signaling molecules, including the Janus kinases (JAKs), which are responsible for its phosphorylation. Furthermore, the context mentions soluble forms of the IL-6 receptor (sIL-6Rα) and soluble gp130 (sgp130), which influence the activity of STAT3 by modulating the availability and activity of the IL-6 signaling complex. + - It also indirectly interacts with acute-phase proteins like C-reactive protein (CRP), with IL-6-induced STAT3 activity leading to increased CRP expression. + +4. **Importance in Biological Systems**: + - STAT3 plays a pivotal role in controlling inflammatory responses, promoting cellular growth and differentiation, particularly in response to IL-6 signaling, a critical regulator in immune responses and inflammation. + - In diseases such as Crohn’s disease, increased levels of pSTAT3 have been associated with disease activity, highlighting its importance in the pathology and as a potential therapeutic target. + +In summary, STAT3 is a central player in the IL-6 signaling pathway, influencing diverse biological processes and contributing to the pathology of various inflammatory diseases. Its regulation and interaction with other components make it a vital molecule in cellular signaling and a focal point in systems biology modeling." +mw39c2e431_fdc3_4964_be29_6ca856620b1b,pSTAT3,"Based on the context provided, pSTAT3 is the phosphorylated form of STAT3 (Signal Transducer and Activator of Transcription 3). Here is a summary of its relevant biological functions and roles based on the provided context and general knowledge: + +1. **Biological Function**: + pSTAT3 is a transcription factor that is activated through phosphorylation. This phosphorylation is primarily mediated by the Janus kinase (Jak) pathway, which is activated upon stimulation by cytokines such as interleukin 6 (IL-6). Once phosphorylated, pSTAT3 dimerizes and translocates to the cell nucleus, where it binds to specific DNA sequences to regulate the transcription of various genes. + +2. **Role in Pathways**: + - **IL-6 Signaling Pathway**: pSTAT3 acts as a critical intermediary in the IL-6 signaling cascade. The context suggests that IL-6 can facilitate pSTAT3 activation through both classical and trans-signaling mechanisms. Trans-signaling involves interactions with soluble IL-6 receptors (sIL-6R), while classical signaling involves membrane-bound IL-6 receptors. + - **JAK/STAT Pathway**: This is the primary signaling pathway for the activation of STAT3, where cytokines activate receptor-associated JAKs, which in turn phosphorylate STAT3, leading to the generation of pSTAT3. + +3. **Interactions with Other Molecules**: + - pSTAT3 interacts with the IL-6 receptor complex, which includes IL-6, sIL-6R, and gp130 (both membrane-bound and soluble forms like sgp130). The complex formation leads to the activation of downstream signaling, with pSTAT3 being a pivotal output molecule that drives gene transcription. + - SOCS (Suppressor of Cytokine Signaling) proteins are notable as negative regulators, limiting the activity of the JAK/STAT pathway and, consequently, pSTAT3 activity. + +4. **Importance in Biological Systems**: + The activation of pSTAT3 is associated with numerous cellular responses, including immune responses, inflammation, cell growth, and differentiation. Its presence and activity level in tissues like the gastrointestinal tract have been linked to inflammatory conditions, such as Crohn's Disease, as indicated by increased pSTAT3 in colon biopsies in such diseases. This highlights its importance in immune regulation and pathology. + +5. **Clinical Relevance**: + Due to its role in promoting inflammatory gene expression and cell proliferation, aberrant or prolonged activation of pSTAT3 is implicated in several diseases, including cancers and inflammatory bowel diseases. Therefore, it is a potential target for therapeutic interventions aimed at modulating immune responses or treating STAT3-driven pathologies. + +In summary, pSTAT3 is a crucial molecule in cytokine signaling pathways, modulating gene expression and contributing to inflammatory and proliferative processes in various tissues. Its regulation, particularly in pathological contexts like inflammatory bowel disease, makes it a significant focus for biological modeling and therapeutic targeting." +mwd5313618_89eb_4c8c_bc82_66f10f966349,CRP,"C-reactive protein (CRP) is a well-known marker in biological systems, particularly for inflammation. In the context of the provided documents, CRP serves as a biomarker to assess inflammation levels and the effectiveness of certain treatments, such as those targeting interleukin-6 (IL-6) signaling pathways in conditions like Crohn's disease. + +**Biological Function:** +CRP is an acute-phase protein produced by the liver. Its levels in the serum increase in response to inflammation caused by various factors, including infections and autoimmune diseases. CRP's primary biological function is to bind to the surface of dead or dying cells and some types of bacteria, thereby activating the complement system, which is a part of the immune response. + +**Role in Pathways:** +CRP is heavily involved in the immune response, mainly through its interaction with IL-6. IL-6 is a cytokine that plays a critical role in inflammation and immune response, and it induces the production of CRP. This connection makes CRP a useful indicator for evaluating the activity of the IL-6 pathway in various diseases. + +**Interactions with Other Molecules:** +- **IL-6 and IL-6Rα:** CRP production is stimulated by IL-6, which binds to IL-6 receptors and activates downstream signaling pathways that include the transcription of acute-phase proteins like CRP. +- **sgp130Fc:** The document mentions the use of sgp130Fc, an antagonist for IL-6 trans-signaling, suggesting interactions that potentially involve modulation of CRP levels when IL-6 signaling is inhibited. + +**Importance in the Biological System Being Modeled:** +CRP is central to the evaluation and modeling of inflammatory responses. In the simulation and modeling context in the document, CRP levels are utilized to validate models predicting the effect of IL-6 pathway inhibitors. Elevated CRP levels are commonly used as a surrogate marker for inflammation, making it a crucial component for assessing and predicting the effectiveness of treatments aimed at reducing inflammatory responses, especially in conditions like Crohn's disease. + +In summary, CRP's role as an indicator of inflammation, particularly through its interaction with the IL-6 pathway, makes it a critical focus in understanding and modeling inflammatory diseases and the effectiveness of treatments targeting these pathways." +mw2e464cf3_a09c_4b7c_9f3c_06720016a48e,sR,"The provided context primarily discusses the involvement of specific molecules and pathways related to the IL-6 signaling system, particularly focusing on the soluble interleukin-6 receptor (sIL-6R) and its interactions within the immune response system. However, it does not specifically mention a species or molecule identified solely as 'sR'. Given the context, it is possible to infer that 'sR' could refer to a soluble receptor component within this framework, possibly related to the IL-6 signaling pathway. + +### Inferred Background Information about 'sR': + +1. **Biological Function:** + - If 'sR' refers to a soluble receptor like sIL-6R, it functions by binding to a cytokine (such as IL-6) and subsequently participating in signaling pathways that alter cellular responses. Soluble receptors often regulate the activity of cytokines by either enhancing their range and stability or modifying their interaction with membrane-bound receptors. + +2. **Role in Pathways:** + - In the context of IL-6 signaling, soluble receptors like sIL-6R can form complexes with IL-6 (IL-6:sR complex), which can interact with other receptor subunits such as the signal-transducing element gp130. This initiates downstream signaling cascades like the JAK/STAT pathway, which affects the expression of various genes involved in inflammation and immune response. + +3. **Interactions with Other Molecules:** + - Potential interactions for 'sR' include binding with cytokines like IL-6 and interacting with other receptor components or proteins such as gp130. The formation of IL-6:sR:sgp130 complexes is one noted interaction, suggesting a role in modifying the cytokine's activity and downstream effects. + +4. **Importance in the Biological System:** + - The presence of soluble receptors modulates the intensity and duration of cytokine signaling. In the context described, the dynamics of 'sR' could be crucial in fine-tuning immune responses, particularly in inflammatory conditions. The precise balance and levels of such components can significantly influence physiological functions and pathological outcomes. + +Overall, while the context does not directly provide information about a species identified as 'sR', based on the descriptions of similar molecules, 'sR' may play a significant modulation role in cytokine signaling, impacting inflammation and immune system behavior." +mw36ea78c1_ed71_4def_96d3_857a442d7195,CRPExtracellular,"The context provided does not specifically mention a species or molecule named 'CRPExtracellular' with the exact ID given. However, based on the context and general biological knowledge, we can infer information about CRP, or C-reactive protein, which is mentioned multiple times. + +CRP, or C-reactive protein, is a protein found in blood plasma, whose levels rise in response to inflammation. It is considered an acute-phase protein produced by the liver in the presence of cytokines, particularly interleukin-6 (IL-6). The following points summarize the potential background information about 'CRPExtracellular' based on the context: + +1. **Biological Function**: CRP plays a critical role in the body's inflammatory response. It binds to the surface of dead or dying cells (and some types of bacteria) to activate the complement system, promoting phagocytosis by macrophages, which is part of the innate immune response. + +2. **Role in Pathways**: CRP is a significant marker in inflammation pathways. The context mentions its suppression as an indicator of the efficacy of treatments targeting IL-6 signaling. The model used in the study predicts serum CRP levels as a marker to assess the impact of drug treatments on inflammatory processes, like those seen in Crohn’s disease. + +3. **Interactions with Other Molecules**: CRP interacts with various components of the immune system, notably through its interaction with the complement system. However, the context primarily focuses on its relationship with IL-6 signaling. Antibodies targeting IL-6 or its receptor are shown to suppress CRP levels in the serum, reducing inflammation. + +4. **Importance in the Biological System Being Modeled**: In the context of the model described, CRP serves as a critical biomarker for inflammation and the efficacy of therapeutic interventions. The suppression of serum CRP levels is used as an output to evaluate the success of different treatment strategies for diseases characterized by overactive inflammation, like Crohn's disease. + +Given this information, 'CRPExtracellular' could refer to the presence of CRP in the extracellular fluid, where it exerts its effects and serves as an important marker for inflammation in the modeling system." +mw147d30ec_478e_4090_b496_128a131d29eb,sgp130,"Based on the provided context, sgp130 appears to be a biological molecule involved in the regulation of IL-6 signaling pathways. Here's a detailed summary of the relevant background information about sgp130: + +1. **Biological Function:** + - sgp130 is a fusion protein that combines the extracellular portion of the glycoprotein gp130 with the Fc region of human IgG1. This fusion protein, referred to as sgp130Fc, functions primarily as an inhibitor of IL-6 trans-signaling. IL-6 is a cytokine that plays a crucial role in immune response, inflammation, and hematopoiesis. + +2. **Role in Pathways:** + - sgp130 is part of the signaling pathways involving IL-6 and its receptor organization. It specifically targets the IL-6/sIL-6Rα complex, preventing the propagation of IL-6 trans-signaling in cells, which can have various downstream effects on immune and inflammatory responses. + +3. **Interactions with Other Molecules:** + - sgp130 interacts with the IL-6/sIL-6Rα complex, binding it with the same affinity as the natural gp130 receptor. This interaction is significant because it hinders the complex's activity in trans-signaling pathways, which are mediated by the presence of soluble IL-6 receptors and contribute to various biological processes, including inflammation. + +4. **Importance in the Biological System Being Modeled:** + - In the context of this specific model, sgp130 plays a role in modulating the IL-6-mediated signaling pathways. However, the sensitivity analysis in the model indicated that altering sgp130 levels has minimal effect on the steady-state values of output parameters due to the excess presence of sgp130 relative to IL-6. Consequently, sgp130-based therapies might be less effective if the goal is to significantly alter these pathways or conditions like Crohn’s disease, as the system shows relative insensitivity to sgp130 changes. + +In conclusion, sgp130 (as part of the sgp130Fc fusion protein) is primarily involved in the inhibition of IL-6 trans-signaling. Still, due to its high baseline level compared to IL-6, its impact on biological system dynamics may be limited without significant changes in sgp130 concentration." +mwab41493c_6349_45f1_a226_3030cfed0e06,sR_IL6_sgp130,"Based on the context provided and general knowledge of similar biological components, the species 'sR_IL6_sgp130' refers to complexes involving soluble IL-6 receptor components and the gp130 receptor protein. Here's a summary of the relevant information regarding these components: + +1. **Biological Function:** + - sR_IL6_sgp130 is likely involved in modulating the IL-6 signaling pathway. IL-6 is a cytokine that plays a critical role in immune responses, inflammation, and hematopoiesis. + +2. **Role in Pathways:** + - The document references IL-6 trans-signaling, it suggests that sR_IL6_sgp130 might be part of the mechanism to inhibit IL-6 signaling pathways. The soluble form of gp130 (sgp130) is noted as a negative regulator of IL-6 trans-signaling, which can act as a natural inhibitor by forming a complex with IL-6 and its soluble receptor sIL-6Rα, thus preventing further activation of membrane-bound gp130 receptor and subsequent signaling cascades. + +3. **Interactions with Other Molecules:** + - The context suggests that sgp130 interacts with the IL-6/sIL-6Rα complex. This interaction is essential because sgp130 cannot bind IL-6 directly unless IL-6 is associated with its soluble receptor, sIL-6Rα. + +4. **Importance in the Biological System Being Modeled:** + - In the context of inhibiting IL-6 trans-signaling, sgp130 (and likely sR_IL6_sgp130) plays a crucial role in maintaining balance by preventing excessive inflammatory responses. The simulations noted in the document suggest that therapeutically targeting sgp130 can have effects only at high doses, implicating its nuanced role in inflammation control through cytokine signaling pathways. + +5. **Modeling and Implications:** + - The system-level model mentioned discusses how sgp130 levels have little impact on steady-state parameters due to its high baseline concentration relative to free IL-6. This indicates sR_IL6_sgp130's role is more pronounced in scenarios where its concentration alters significantly, such as therapeutic applications for diseases like Crohn’s disease. + +In summary, sR_IL6_sgp130 is integral to the regulation of IL-6 signaling, primarily acting as an inhibitor in inflammatory processes, and its high natural abundance helps modulate these pathways under normal physiological conditions. +" +mwf405687b_7401_44ec_a0d6_4a2b35c13e8a,Ab_sR,"Based on the provided context, there is no direct mention or specific information about the species 'Ab_sR' with ID: mwf405687b_7401_44ec_a0d6_4a2b35c13e8a. However, we can infer potential characteristics and roles of 'Ab_sR' by examining the context, which discusses interleukin-6 (IL-6) signaling pathways and associated molecules like soluble IL-6 receptor (sIL-6R) and C-reactive protein (CRP). + +### Inferred Background Information about Ab_sR: + +1. **Biological Function:** + - If 'Ab_sR' is involved in the context of IL-6 signaling, it might be a receptor or a binding protein similar to sIL-6R. Soluble receptors often regulate cytokine activity by modulating their availability or by forming complexes that can engage in signaling. + +2. **Role in Pathways:** + - In the IL-6 signaling pathway, sIL-6R can form a complex with IL-6 that can interact with the signaling receptor gp130, initiating intracellular signaling cascades such as the JAK/STAT pathway. If 'Ab_sR' is analogous, it could play a role in modulating or facilitating such pathways. + +3. **Interactions with Other Molecules:** + - 'Ab_sR' may interact with cytokines like IL-6, potentially forming complexes that affect downstream signaling processes. Interaction with other receptors or signaling proteins such as gp130 is also a possibility if 'Ab_sR' serves a regulatory or modulating function similar to sIL-6R. + +4. **Importance in the Biological System:** + - In a biological system involving IL-6, components like sIL-6R are crucial for modulating inflammatory responses, highlighting their importance in immune regulation. Therefore, if 'Ab_sR' is part of this system, it may contribute significantly to balancing inflammatory signals and could be a target for therapeutic interventions aimed at controlling excessive inflammation. + +Given the context's focus on IL-6 and its receptors, 'Ab_sR' might represent a component analogously involved in modifying immune responses or influencing chronic inflammation states, similar to how the sIL-6R functions in IL-6 signaling pathways." +mw3667a5e1_02c9_44a0_acb4_b0431faa822d,Ab,"The species denoted as 'Ab' in the context appears to refer to an antibody. Specifically, this antibody seems to play a role in targeting and potentially neutralizing components involved in inflammatory pathways. + +### Biological Function: +- The context suggests that 'Ab' is an antibody directed against interleukin-6 (IL-6) or its receptor(s), particularly the soluble IL-6 receptor alpha (sIL-6Rα). Antibodies in this context are proteins designed to bind to specific antigens, such as IL-6 or its receptor, effectively inhibiting their activity. + +### Role in Pathways: +- The 'Ab' functions by engaging with and targeting the IL-6/sIL-6Rα complex, as part of a therapeutic mechanism aimed at reducing inflammation. This is evidenced by its usage in experiments modeling responses to treatment in conditions such as inflammatory bowel diseases (as indicated in other parts of the document). +- The targeting of this complex by the antibody is aimed at modulating immune responses, as IL-6 is a cytokine implicated in inflammatory and immune signaling pathways. + +### Interactions with Other Molecules: +- The antibody ('Ab') interacts specifically with IL-6 and sIL-6Rα. This interaction is significant because it prevents IL-6 from exerting its pro-inflammatory effects by blocking its interaction with cellular receptors or neutralizing it directly in circulation. +- The context also describes a dose-response relationship with serum C-reactive protein (CRP) suppression, which further underscores the antibody's role in inflammation modulation. CRP is an inflammatory marker, whose levels decrease with effective IL-6 pathway inhibition. + +### Importance in the Biological System Being Modeled: +- 'Ab' is essential in the system due to its therapeutic potential in inflammatory diseases. By inhibiting IL-6 and its receptor's interaction, the antibody can help reduce pathological inflammation. +- This is particularly relevant in clinical scenarios where overactive IL-6 signaling contributes to disease progression, such as in certain autoimmune or inflammatory conditions. + +Overall, 'Ab' is a critical component in the strategy for modulating inflammatory responses, highlighting its importance in both research and potential therapeutic applications." +mw772cbf20_3fc1_4800_ae59_77884f1ae333,Ab_R,"Based on the provided context from the documents, there is no specific mention or description of a biological species or molecule directly named 'Ab_R' with the ID provided. However, due to the context and typical content of systems biology research, we can infer some possibilities regarding what 'Ab_R' might represent, particularly in relation to antibodies or related biological components: + +1. **Biological Function**: Given the context involving antibodies and their interactions with IL-6 receptors, 'Ab_R' could likely denote an antibody or a component related to antibody functions. Antibodies (Ab) are crucial components of the immune system, responsible for identifying and neutralizing foreign objects such as bacteria and viruses. + +2. **Role in Pathways**: If 'Ab_R' is an antibody, it may play a role in immune signaling pathways, potentially as a therapeutic target or agent. Antibodies can either directly neutralize targets like IL-6 or IL-6Rα, or they can modulate signaling pathways by preventing these components from interacting and inducing inflammatory responses. + +3. **Interactions with Other Molecules**: The documents discuss anti–IL-6 and anti–IL-6Rα antibodies, as well as their interactions and dose responses. If 'Ab_R' is related to these antibodies, it might interact with interleukins or receptors involved in inflammatory responses, specifically IL-6 and its receptor IL-6Rα, affecting pathways such as cytokine signaling and inflammation regulation. + +4. **Importance in the Biological System Being Modeled**: In systems biology models, antibodies like 'Ab_R' can serve as model variables for predicting efficacy and outcomes of treatments targeting inflammatory pathways, such as those associated with chronic inflammatory diseases. The importance lies in their ability to modulate pivotal biochemical pathways, reduce inflammation markers such as CRP (C-reactive protein), and provide insights into therapeutic strategies. + +In conclusion, without explicit information regarding 'Ab_R', the inference is that it might be an antibody related to the systems being studied, possibly playing a role in modulating inflammation through interactions with components like IL-6 and IL-6Rα." +mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf,Ab_sR_IL6,"Based on the context provided, there is no explicit mention of a species or molecule named 'Ab_sR_IL6' with the ID mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf. However, the documents discuss the interactions of antibodies with the IL-6/sIL-6Rα complex and the effects of targeting this interaction on immune regulation, specifically mentioning IL-6 and IL-6 receptor components such as sIL-6R (soluble IL-6 receptor). + +Given this context, we can infer that 'Ab_sR_IL6' might represent an antibody related to the IL-6/sIL-6R interaction. Here is a generalized summary based on related knowledge about antibodies targeting the IL-6 pathway: + +### Background Information on Potential 'Ab_sR_IL6': + +- **Biological Function:** 'Ab_sR_IL6' is likely an antibody that targets the IL-6 signaling pathway, possibly binding to the soluble IL-6 receptor (sIL-6R) to modulate the interaction between IL-6 and its receptor. + +- **Role in Pathways:** This antibody would play a role in interrupting or modulating the IL-6 signaling pathway, which is involved in various immune and inflammatory responses. By targeting sIL-6R, the antibody may inhibit downstream signaling events, such as the activation of STAT3 and subsequent transcription of inflammatory gene products. + +- **Interactions with Other Molecules:** 'Ab_sR_IL6' may interact with sIL-6R, possibly preventing its interaction with IL-6 and the membrane-bound IL-6 receptor, thus affecting the formation of the IL-6/sIL-6R complex and its role in inflammatory signaling. + +- **Importance in the Biological System:** The antibody's potential inhibition of IL-6 signaling can be critical in controlling overactive immune responses associated with diseases like Crohn’s disease and rheumatoid arthritis. By moderating this pathway, 'Ab_sR_IL6' may contribute to the suppression of inflammatory markers such as C-reactive protein (CRP). + +This inference is made based on the context of targeting IL-6/sIL-6R pathways in therapeutic models and the general strategy of using monoclonal antibodies to modulate immune-related pathways." +mw7becb5fe_8da8_4285_a821_0d77ad811b62,sR_IL6,"Based on the context provided, specific information about the species named 'sR_IL6' (ID: mw7becb5fe_8da8_4285_a821_0d77ad811b62) is not directly mentioned. However, we can infer information based on the context regarding similar molecules like IL-6 and sIL-6R. + +### General Inference on sR_IL6: + +1. **Biological Function:** + - IL-6 is a cytokine involved in immune response regulation, often signaling through pathways that involve soluble receptors, such as sIL-6R (soluble interleukin-6 receptor). + - sIL-6R itself is instrumental in extending the range of IL-6 signaling to cells that do not naturally express the membrane-bound IL-6 receptor. + +2. **Role in Pathways:** + - IL-6 can signal through two main pathways: classical signaling, where it binds to membrane-bound IL-6R, and trans-signaling, involving sIL-6R. + - The IL-6/sIL-6R complex can be sequestered by sgp130, a soluble protein that modulates these pathways. + - These pathways are crucial in inflammation and immune regulation, often involved in diseases like Crohn's disease. + +3. **Interactions with Other Molecules:** + - IL-6 interacts with sIL-6R to form a complex that can engage with other components like gp130 (glycoprotein 130) to facilitate signaling. + - The context also suggests interactions with pharmacological agents, with antibody treatments targeting IL-6 or the IL-6/sIL-6R complex showing varying efficacy. + +4. **Importance in the Biological System:** + - In models focusing on immune regulation, especially in conditions like Crohn's disease, the IL-6/sIL-6R axis is critically evaluated for therapeutic targeting. + - Understanding its role is key for developing treatments that modulate immune responses pathological conditions. + +Overall, while 'sR_IL6' is not explicitly detailed in the documents, it can be inferred to have a function and role akin to soluble receptors facilitating cytokine signaling, with critical implications in inflammatory disease models." +mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca,gp130,"Gp130, also known as glycoprotein 130, is a crucial component of the interleukin-6 (IL-6) signaling pathway. It functions as a signal transducer in the receptor complex for IL-6, which plays a pivotal role in immune response, inflammation, and hematopoiesis. Gp130 itself does not bind IL-6 directly; instead, it forms part of the high-affinity receptor complex by associating with the IL-6/IL-6 receptor (IL-6R) complex. + +In the context of IL-6 signaling, gp130 is involved in classical signaling where it forms a hexameric structure with IL-6 and its membrane-bound IL-6R. Gp130 is also involved in trans-signaling, particularly through its interaction with soluble IL-6 receptor (sIL-6R). In this process, IL-6 can bind to sIL-6R, and the complex can then associate with gp130 on cells that do not express IL-6R, thereby expanding the range of cells responsive to IL-6 signaling. + +The document mentions a fusion protein, sgp130Fc, designed to inhibit IL-6 trans-signaling. This suggests that soluble gp130 (sgp130) acts as a natural inhibitor of the IL-6/sIL-6R complex, potentially preventing it from binding to membrane-bound gp130, thereby attenuating downstream signaling. This property of sgp130 is being explored as a therapeutic approach for conditions like Crohn's disease. + +In terms of its biological importance, gp130 is crucial for mediating normal and pathological responses through the IL-6 pathway. Its interactions with IL-6 and IL-6R complexes make it a significant player in inflammatory diseases and a potential target for therapeutic interventions aimed at modulating immune responses." +mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9,R_IL6_gp130,"Based on the context provided, it appears there is limited direct information about the species 'R_IL6_gp130' with the ID provided. However, we can synthesize and infer its role based on related information about similar biological components. + +### Inferred Background Information about R_IL6_gp130: + +- **Biological Function**: The naming 'R_IL6_gp130' suggests a complex involving Interleukin-6 (IL-6) and glycoprotein 130 (gp130). IL-6 is a cytokine involved in inflammatory and immune responses. gp130 is a signal transducing component of the IL-6 receptor complex. The complex's primary function is to mediate IL-6 signaling, which is crucial for the acute phase response and in regulating the immune and inflammatory responses. + +- **Role in Pathways**: The IL-6/gp130 complex is involved in the signaling pathways that result in the activation of intracellular cascades such as the JAK/STAT pathway. This signaling is essential for modulating gene expression in various tissues and contributes to physiological and pathophysiological processes. Specifically, the IL-6/gp130 signaling pathway plays a significant role in the inflammatory response observed in diseases like Crohn's disease, as noted in the context. + +- **Interactions with Other Molecules**: The context notes soluble forms of the receptor components, such as sgp130 and sIL-6R. These soluble factors can modulate IL-6 signaling by acting as competitive antagonists or facilitators of trans-signaling. The IL-6 can bind to its soluble receptor (sIL-6R), and the complex can then associate with both membrane-bound and soluble gp130 (sgp130) to continue the signal transduction process. + +- **Importance in the Biological System**: The IL-6/gp130 signaling complex is crucial in managing systemic inflammatory responses and its dysregulation can lead to chronic inflammatory conditions. It is an important therapeutic target, as seen in the research modeling the use of sgp130Fc to inhibit IL-6 trans-signaling for treating conditions like Crohn's disease. + +Overall, R_IL6_gp130 likely represents a functional interaction or complex in the IL-6 signaling pathway that plays a pivotal role in immune responses and inflammation. It is essential for understanding disease pathogenesis and designing therapeutic interventions targeting cytokine signaling." +mw6cce2109_0e32_4dd9_98ec_41173e8ef07d,Ractive,"The provided context does not contain direct information about the species named 'Ractive' with the specified ID. However, based on the context, which discusses a multiscale model of IL-6–mediated immune regulation in Crohn's Disease and involves components such as IL-6, IL-6Rα, and antibodies targeting these molecules, we can make some inferences. + +1. **Biological Function**: Ractive might be a signaling molecule or a biological entity involved in immune regulation, potentially analogous to IL-6 or its receptor. Its function could involve modulation of immune responses, particularly in inflammatory conditions such as Crohn's disease or rheumatoid arthritis. + +2. **Role in Pathways**: If Ractive functions similarly to IL-6 or its receptor, it may play a role in cytokine signaling pathways, which are crucial for immune system communication and regulation. These pathways often involve complex interactions and feedback mechanisms that control inflammation and immune response. + +3. **Interactions with Other Molecules**: Ractive could interact with receptors or form complexes that facilitate or inhibit signal transduction. This is akin to how IL-6 interacts with sIL-6Rα, forming a complex that can activate signaling pathways. + +4. **Importance in the Biological System**: In a model of immune regulation, Ractive could be important for understanding the dynamics of immune signaling, potentially serving as a target for therapeutic interventions in diseases characterized by dysregulated immune responses. + +Without specific information, these inferences rely on general knowledge of molecules involved in cytokine signaling and immune modulation, similar to IL-6 and its receptor pathways." +mw2b255f94_8018_4b99_bde8_918eeac45446,STAT3,"STAT3, or Signal Transducer and Activator of Transcription 3, is a transcription factor involved in various biological processes, particularly in signal transduction pathways. It is activated through phosphorylation, which is triggered by upstream cytokine signaling, such as the interleukin-6 (IL-6) signaling pathway. This phosphorylation site on STAT3 is known as pSTAT3, where 'p' denotes its phosphorylated state. + +**Biological Function:** +STAT3 serves as a key mediator in the cytokine signaling pathway that leads to the transcription of various genes. Upon activation, STAT3 translocates to the nucleus where it binds to specific DNA sequences to induce gene expression. The genes regulated by STAT3 are often involved in crucial biological processes such as immune response, cell growth, apoptosis, differentiation, and inflammation. + +**Role in Pathways:** +STAT3 is prominently involved in the IL-6 signaling cascade. Within this pathway, IL-6 binding leads to the formation of a receptor complex that includes IL-6Rα and gp130, which then activates associated Janus kinases (JAKs). The JAK kinases phosphorylate STAT3, enabling its dimerization and subsequent nuclear translocation. In the nucleus, STAT3 acts on specific response elements to modulate the expression of target genes. + +**Interactions with Other Molecules:** +STAT3 interacts with various components of the IL-6 signaling pathway, including the IL-6/sIL-6Rα complex and the gp130 receptor. Additionally, soluble gp130 (sgp130) can act as an inhibitor by sequestering the IL-6/sIL-6Rα complex, thereby modulating STAT3 activation. STAT3’s interactions are critical in modulating the inflammatory response as well as acute-phase reactions. + +**Importance in Biological Systems:** +In the context of disease, STAT3-mediated trans-signaling is significant, particularly because it is involved in the upregulation of acute-phase proteins like C-reactive protein (CRP) and in immune responses within tissues such as the gastrointestinal tract and liver. Aberrant STAT3 signaling has been implicated in various pathological conditions, including cancers and inflammatory disorders like Crohn’s disease. In these contexts, STAT3's regulatory role on gene expression can impact cellular proliferation and differentiation, making it a valuable target for therapeutic interventions." +mw48867e93_f170_44e8_ac7a_185b23e1bf3b,pSTAT3,"pSTAT3, or phosphorylated Signal Transducer and Activator of Transcription 3, is a key molecule in the realm of cellular biology, particularly in the context of its involvement in various signaling pathways. Based on the provided context, here is a summary of pSTAT3's roles and interactions: + +1. **Biological Function:** + pSTAT3 is a phosphorylated form of the STAT3 protein, which functions as a transcription factor. Once activated, it translocates to the cell nucleus where it influences the transcription of various genes. This process is crucial for mediating cellular responses to cytokines and growth factors. + +2. **Role in Pathways:** + The context mentions pSTAT3 in connection with the IL-6 signaling pathway. IL-6 binds to its receptor IL-6R, and through the co-receptor gp130, initiates signaling cascades that lead to the activation (phosphorylation) of STAT3. This activation is implicated in ""trans-signaling"" which is a form of signaling where the ligand-receptor complex activates cells that do not express the IL-6 receptor. + +3. **Interactions with Other Molecules:** + pSTAT3 is involved in a sophisticated network of interactions: + - It is downstream of the IL-6 signaling pathway, activated upon IL-6 binding to its receptor complex. + - The phosphorylated STAT3 can induce expression of various genes including those encoding the suppressor of cytokine signaling (SOCS) proteins, which are negative regulators of cytokine signaling. + - The context implies interactions with soluble forms of IL-6 receptor components, like sIL-6R and sgp130, which affect the signaling outcomes. + +4. **Importance in the Biological System:** + pSTAT3 is highlighted as an important signaling molecule in inflammatory responses, as noted in the mention of Crohn’s disease, an inflammatory bowel condition. In this context, elevated levels of pSTAT3 in colon biopsies suggest its role in mediating inflammatory processes. This underlines its importance not only in normal physiological responses but also in pathological conditions, making it a potential target for therapeutic intervention. + +Overall, pSTAT3 plays a vital role in cytokine signaling pathways, particularly those involving IL-6, and is crucial for cellular functions that relate to inflammation, differentiation, and immune responses." +mw0083d743_836f_4238_a17f_4602193d5bc0,geneProduct,"The context provided does not specifically mention the species or molecule identified by the name 'geneProduct' with the ID mw0083d743_836f_4238_a17f_4602193d5bc0. However, based on the context surrounding interactions with IL-6, sIL-6R, and sgp130, we can infer some potential roles and characteristics that a typical gene product may exhibit within this biological system, particularly related to IL-6 signaling. + +1. **Biological Function**: + - The reference to various gene products in conjunction with IL-6 pathways suggests that geneProduct might be involved in signaling pathways or could encode proteins that participate in immune responses. IL-6 is known to be a cytokine that plays a significant role in inflammation and the immune response. + +2. **Role in Pathways**: + - Gene products in the context of IL-6 are likely to be involved in mediating inflammatory responses or immune regulation. They could be participating in pathways involving Jak-STAT signaling, which is mentioned alongside IL-6 signaling processes in the text. + +3. **Interactions with Other Molecules**: + - The gene product could potentially interact with components of the IL-6 signaling pathway, such as the IL-6 receptor (IL-6R), soluble IL-6R (sIL-6R), and the signal transducer gp130. These interactions could influence downstream signaling cascades leading to diverse cellular responses. + +4. **Importance in the Biological System Being Modeled**: + - Considering the text emphasizes IL-6 signaling and its regulatory mechanisms, the gene product likely holds importance in modulating immune responses or inflammation. It might contribute to the fine-tuning of the system's response to inflammatory stimuli or be a target for therapeutic interventions to manage conditions related to excessive inflammation. + +Although specific details about the geneProduct are not mentioned in the provided context, understanding general roles of other gene products in similar pathways suggests potential functions and interactions that could be applicable." +mwd31f52cc_04e7_40e0_885f_c7b2d9e62215,sR,"Based on the provided context, the species named 'sR' appears to be associated with IL-6 signaling pathways. While the document doesn't explicitly detail the specific properties or function of 'sR', we can infer its potential role from related components mentioned, such as sIL-6R and sgp130. + +1. **Biological Function and Role in Pathways**: + - **sR** likely stands for a soluble receptor, analogous to sIL-6R (soluble Interleukin-6 Receptor), a well-known component in the IL-6 signaling pathway. + - Soluble receptors like sIL-6R can enhance the spectrum of the cytokine's action, allowing IL-6 to affect cells that do not express membrane-bound receptors. + - In the IL-6 signaling pathway, these molecules participate in the ""trans-signaling"" mechanism, where soluble receptors (e.g., sIL-6R) bind to IL-6, and this complex can then interact with membrane-bound gp130 on cells, initiating downstream signaling events. + +2. **Interactions with Other Molecules**: + - The context mentions interactions between IL-6, sIL-6R, and sgp130. It's likely that 'sR' interacts with one or more of these molecules, possibly forming a complex with IL-6 that subsequently engages with cell surface components like gp130. + - sgp130 acts as a natural inhibitor in the IL-6 signaling pathway by competitively inhibiting the binding of the IL-6/sIL-6R complex to cell surface gp130, thus regulating IL-6 trans-signaling activities. + +3. **Importance in the Biological System**: + - While the specific importance of 'sR' is not detailed, by analogy to sIL-6R, it could be critical in mediating and regulating responses to IL-6 in varied tissues, influencing gene expression changes and physiological responses. + - Alterations in its concentration, similar to sgp130, may have implications for the dynamics of the signaling pathway, with potential roles in inflammatory responses, metabolism, or immune regulation. + +In summary, although 'sR' is not specifically described, it is likely a component similar to sIL-6R, involved in facilitating IL-6 signaling through the trans-signaling pathway, with important interactions and regulatory roles in biological systems involving inflammatory responses." +mw2c9b0499_3325_4394_8af3_bbf653a944a0,IL6,"Based on the provided context, here is the background information about the molecule IL-6: + +### Biological Function +IL-6 (Interleukin 6) is a cytokine that plays a crucial role in immune regulation. It is involved in various immune responses, inflammation, and hematopoiesis (formation of blood cellular components). + +### Role in Pathways +IL-6 can signal through two main pathways: +1. **Classical Signaling Pathway:** Involves the membrane-bound IL-6 receptor (IL-6Rα). IL-6 binds to IL-6Rα, forming a dimer, which then associates with the gp130 receptor to form a hexameric complex. This complex triggers the phosphorylation of Janus kinase (Jak) family proteins and subsequently activates the STAT3 (Signal Transducer and Activator of Transcription 3) pathway. +2. **Trans-signaling Pathway:** Involves the soluble IL-6 receptor (sIL-6Rα). IL-6 binds to sIL-6Rα, and this complex interacts with gp130 on cell surfaces, similarly initiating the Jak/STAT3 signaling cascade. + +### Interactions with Other Molecules +IL-6 interacts with both its membrane-bound and soluble receptors (IL-6Rα and sIL-6Rα) to mediate its biological effects. The subsequent activation of gp130 and Jak/STAT3 signaling pathways is a key interaction. IL-6 also interacts with antibodies that target either IL-6 itself or its receptor, influencing signal suppression, which has therapeutic implications. + +### Importance in the Biological System Being Modeled +In the context of Crohn’s Disease, IL-6 is a significant contributor to the disease pathology. It enhances T-cell survival and apoptosis resistance in the intestinal lamina propria, leading to increased secretion of chemokines. This exacerbates the inflammatory response, making IL-6 a critical target for therapeutic interventions in Crohn's Disease. The suppression of IL-6 signaling through antibodies such as tocilizumab is of interest in controlling disease progression. + +This information contextualizes the role of IL-6 in immune modulation, particularly its contribution to inflammatory diseases such as Crohn's Disease, and underscores its importance as a therapeutic target." +mwd65b5b39_dc1b_4e77_a999_67277a880e5e,sgp130,"sgp130, as described in the context, refers to a biological molecule associated with the inhibition of IL-6 trans-signaling. It is a fusion protein that combines the extracellular portion of gp130 with the Fc region of human IgG1, known as sgp130Fc. This fusion protein has been experimentally shown to inhibit the IL-6/sIL-6Rα complex in cultured cells. sgp130 acts by binding to this complex, thus playing a role in modulating inflammatory pathways that are mediated by IL-6 trans-signaling. + +The molecule is particularly relevant in the context of therapeutic approaches for inflammatory diseases such as Crohn's disease. The document mentions simulations of intravenous dosing of sgp130Fc, which highlight its therapeutic potential, although its effectiveness is noted to be significant only at high and frequent doses. This suggests a potential therapeutic limitation due to the high baseline level of sgp130 in comparison to free IL-6, indicating that small changes in sgp130 levels have a minimal effect on system dynamics. + +In terms of its role in biological pathways, sgp130's primary function in this context is the regulation of the IL-6 trans-signaling pathway. It interacts specifically with the IL-6/sIL-6Rα complex, preventing the signaling cascade that would normally be activated by the interaction of IL-6 with its receptors. This interaction is crucial for reducing inflammation, especially in cases like Crohn's disease. + +In summary, sgp130 is important in systems biology as an inhibitor of the IL-6 trans-signaling pathway, possessing potential therapeutic uses in inflammatory diseases. However, its effectiveness is contingent upon achieving high concentrations due to its already high baseline levels compared to IL-6, thus making its role in modulating the pathway somewhat limited under normal physiological conditions." +mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3,sR_IL6_sgp130,"The species 'sR_IL6_sgp130' likely refers to a soluble form of the glycoprotein gp130 that interacts with the interleukin-6 (IL-6) signaling complex. From the context provided, it can be inferred that sR_IL6_sgp130 is involved in the inhibition of IL-6 trans-signaling pathways. Here is a breakdown of the potential role and importance of sR_IL6_sgp130 based on the provided text and general biological knowledge: + +1. **Biological Function**: sR_IL6_sgp130 likely functions as an inhibitor of the IL-6 trans-signaling pathway. Trans-signaling involves the interaction of IL-6 with its soluble receptor sIL-6Rα, which can then associate with membrane-bound or soluble gp130 to activate signaling. The role of sR_IL6_sgp130 would be to interrupt this process, thus modulating the cellular response to IL-6. + +2. **Role in Pathways**: In the context of IL-6 signaling, gp130 is a signal-transducing receptor component. Inhibition of the IL-6/sIL-6Rα complex formation by sR_IL6_sgp130 would prevent downstream signaling events such as the activation of the JAK/STAT pathway and its associated transcriptional activities (e.g., induction of CRP production in the liver). + +3. **Interactions with Other Molecules**: sR_IL6_sgp130 interacts directly with the IL-6/sIL-6Rα complex. By binding to this complex, it prevents the engagement and activation of membrane-bound gp130, thereby inhibiting downstream signaling. + +4. **Importance in the Biological System**: The document suggests that while sR_IL6_sgp130 (or sgp130Fc, a pharmacological derivative) can inhibit IL-6-driven signaling pathways, its effectiveness is contingent on very high concentrations due to the high baseline levels of sgp130 compared to IL-6. This implies that sR_IL6_sgp130 serves as a regulatory element within the immune signaling framework, potentially acting as a buffer or modulator to prevent excessive or aberrant IL-6 signaling, which is relevant in pathologies like inflammation or autoimmune diseases. + +In summary, sR_IL6_sgp130 plays a role as a modulator in IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, thus preventing further signal transduction through gp130-mediated pathways. While it has potential therapeutic implications, particularly in inflammatory conditions, its impact in the modeled biological system requires larger perturbations to observe significant effects due to its existing baseline levels." +mwf7796221_1fea_4274_a93e_c00adbf5778c,Ab,"Based on the provided context, there is no direct mention of the species 'Ab' with the ID 'mwf7796221_1fea_4274_a93e_c00adbf5778c'. However, the context provides information on antibody interactions, specifically related to IL-6 and IL-6 receptor α (IL-6Rα), suggesting that 'Ab' might refer to an antibody involved in such interactions. Here’s an inferred background based on the context: + +1. **Biological Function**: The abbreviation 'Ab' often refers to an antibody. Antibodies are crucial components of the immune system, responsible for identifying and neutralizing pathogens like bacteria and viruses. In this context, 'Ab' could be an antibody targeting IL-6 or its receptor IL-6Rα. + +2. **Role in Pathways**: IL-6 is a cytokine involved in various inflammatory and immune responses. The IL-6/IL-6Rα pathway is significant in inflammatory diseases. An antibody against IL-6 or IL-6Rα would play a role in modulating this pathway, potentially reducing inflammation by inhibiting the activity of IL-6. + +3. **Interactions with Other Molecules**: The 'Ab' in the context likely interacts with IL-6 and its receptor IL-6Rα. This interaction is aimed at blocking the cytokine signaling pathway, thereby reducing inflammation and associated symptoms. The context suggests that targeting both IL-6 and the IL-6/IL-6Rα complex can lead to enhanced therapeutic efficacy. + +4. **Importance in the Biological System**: In the biological model described, the antibody 'Ab' plays a critical therapeutic role. By targeting IL-6 and IL-6Rα, it helps manage conditions characterized by excessive inflammation, such as inflammatory bowel diseases, which aligns with the reference to changes in serum CRP (C-reactive protein) levels—a marker of inflammation response. + +In summary, although specific details about the species 'Ab' are not provided, it is likely an antibody functioning within an inflammatory pathway, targeting IL-6 and its receptor to mitigate inflammatory responses in diseases such as inflammatory bowel disease." +mw5d764bb8_5693_4ac8_9557_f65992cc5eb0,Ab_sR,"The provided context does not include specific information about the species named 'Ab_sR' (ID: mw5d764bb8_5693_4ac8_9557_f65992cc5eb0). However, I can infer some possibilities based on general knowledge about similar biological components within the described context. + +1. **Biological Function**: There is a mention of molecules like sIL-6R and IL-6Rα within the text. Typically, 'Ab' in 'Ab_sR' could refer to an antibody or related molecule. In biological systems, antibodies play a crucial role in the immune response by identifying and neutralizing foreign objects like bacteria and viruses. + +2. **Role in Pathways**: If 'Ab_sR' is an antibody, it may be involved in regulatory or signaling pathways. The context discusses the IL-6 signaling pathway, which is important for immune response mediation. Antibodies can modulate such pathways by targeting cytokines or their receptors to either promote or inhibit responses. + +3. **Interactions with Other Molecules**: The IL-6/sIL-6R complex is a subject of interest in the provided context, often interacting with other proteins like sgp130. Antibodies typically interact with antigens (specific target molecules), possibly modulating interactions between cytokines and their receptors or further downstream signaling molecules such as STAT3. + +4. **Importance in the Biological System Being Modeled**: In the given context, antibodies targeting components of the IL-6 pathway are evaluated for their potential in therapy (like CRP suppression), indicating the importance of these molecules in modulating inflammatory responses. Antibodies can be crucial in therapeutically managing conditions involving dysregulated cytokine signaling. + +Without specific information about 'Ab_sR', it is not possible to ascertain its precise function or interactions. However, based on the context involving IL-6 signaling and the mention of antibodies (likely abbreviation 'Ab'), 'Ab_sR' might be involved in similar biological processes." +mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2,Ab_sR_IL6,"The species ""Ab_sR_IL6"" appears to be involved in interactions with the soluble form of the interleukin-6 receptor (sIL-6Rα). Based on the context provided, and given the naming convention (Ab typically denotes an antibody), ""Ab_sR_IL6"" likely represents an antibody that targets the sIL-6Rα molecule. Although there is no explicit mention of ""Ab_sR_IL6"" in the documents, we can infer its role based on known biological interactions and the surrounding text. + +### Inferred Background Information about Ab_sR_IL6: + +1. **Biological Function**: + - ""Ab_sR_IL6"" is likely an antibody designed to interact with the soluble form of the interleukin-6 receptor, sIL-6Rα. Antibodies targeting cytokine receptors are typically used to modulate signal transduction pathways and manage inflammatory responses. + +2. **Role in Pathways**: + - The potential pathway involvement of ""Ab_sR_IL6"" is connected to the IL-6 signaling pathway. By targeting sIL-6Rα, this antibody may influence the downstream signaling of IL-6, a cytokine involved in immune regulation and inflammatory processes. + +3. **Interactions with Other Molecules**: + - It is likely that ""Ab_sR_IL6"" interacts specifically with sIL-6Rα, preventing its interaction with IL-6. This action could block or reduce the IL-6/sIL-6Rα complex formation, thereby affecting the downstream activation of signal transducer and activator of transcription 3 (STAT3) and other related genes and proteins. + +4. **Importance in the Biological System Being Modeled**: + - The targeting of the IL-6/sIL-6Rα complex is significant in the context of diseases characterized by exaggerated IL-6 signaling, such as Crohn's disease and rheumatoid arthritis. Antibodies like ""Ab_sR_IL6"" play a crucial role in diminishing the inflammatory response, potentially leading to decreased C-reactive protein (CRP) levels and amelioration of disease symptoms. + +In summary, while ""Ab_sR_IL6"" is not explicitly detailed in the provided documents, its inferred role as an antibody against sIL-6Rα suggests its importance as a therapeutic agent in managing IL-6 mediated pathways and inflammatory conditions." +mwbc2f5464_81e5_43fd_8b39_f5a2756af72f,Ab,"The provided documents include information that suggests 'Ab' refers to an antibody involved in targeting the interleukin-6 receptor (IL-6Rα) and its soluble form (sIL-6Rα). Here's a summary based on the context: + +### Biological Function +- **Ab** appears to be an antibody that specifically targets the IL-6 receptor (both membrane-bound and soluble forms, IL-6Rα/sIL-6Rα). +- It plays a role in modulating the immune response by interfering with the IL-6 signaling pathway. + +### Role in Pathways +- IL-6 is a cytokine involved in inflammatory and immune responses. The IL-6 receptor, which 'Ab' targets, is part of this pathway. +- Targeting both IL-6 and IL-6Rα/sIL-6Rα can enhance the suppression of CRP (C-reactive protein), a marker of inflammation, indicating that 'Ab' is involved in controlling inflammatory responses. + +### Interactions with Other Molecules +- The context suggests that 'Ab' interacts with IL-6, IL-6Rα, and sIL-6Rα. By binding these molecules, the antibody can alter their function, essentially blocking the downstream signaling of the IL-6 pathway. + +### Importance in the Biological System +- The use of this antibody ('Ab') represents a therapeutic strategy to dampen inflammatory responses, which could be important in treating inflammatory conditions or diseases such as inflammatory bowel diseases, as suggested by the context. +- The document discusses the antibody's dose-response effect on CRP suppression, highlighting its therapeutic potential in modifying disease progression or symptoms. + +In summary, 'Ab' is an antibody participating in anti-inflammatory processes by targeting and inhibiting key components of the IL-6 signaling pathway. This interaction plays a significant role in reducing inflammation and is relevant in pharmacological interventions for diseases characterized by elevated IL-6 activity." diff --git a/docs/notebooks/talk2knowledgegraphs/tutorial_primekg_subgraph.ipynb b/docs/notebooks/talk2knowledgegraphs/tutorial_primekg_subgraph.ipynb index 4c97f708..3ef5b682 100644 --- a/docs/notebooks/talk2knowledgegraphs/tutorial_primekg_subgraph.ipynb +++ b/docs/notebooks/talk2knowledgegraphs/tutorial_primekg_subgraph.ipynb @@ -4764,7 +4764,7 @@ ], "metadata": { "kernelspec": { - "display_name": "venv", + "display_name": "Python 3 (ipykernel)", "language": "python", "name": "python3" }, @@ -4778,9 +4778,9 @@ "name": "python", "nbconvert_exporter": "python", "pygments_lexer": "ipython3", - "version": "3.12.9" + "version": "3.10.14" } }, "nbformat": 4, - "nbformat_minor": 2 + "nbformat_minor": 4 } diff --git a/notebook/embeddings_and_evaluation.ipynb b/notebook/embeddings_and_evaluation.ipynb new file mode 100644 index 00000000..eef48a46 --- /dev/null +++ b/notebook/embeddings_and_evaluation.ipynb @@ -0,0 +1,8407 @@ +{ + "cells": [ + { + "cell_type": "code", + "execution_count": 20, + "id": "d351ee6b-d9da-493b-b072-1dc8380307f3", + "metadata": {}, + "outputs": [], + "source": [ + "# Import necessary libraries\n", + "import os\n", + "import numpy as np\n", + "import pandas as pd\n", + "import networkx as nx\n", + "import pickle\n", + "from tqdm import tqdm\n", + "from torch_geometric.utils import from_networkx\n", + "import sys\n", + "sys.path.append('..')\n", + "from aiagents4pharma.talk2knowledgegraphs.datasets.primekg import PrimeKG\n", + "from aiagents4pharma.talk2knowledgegraphs.datasets.starkqa_primekg import StarkQAPrimeKG\n", + "from aiagents4pharma.talk2knowledgegraphs.utils.embeddings.ollama import EmbeddingWithOllama\n", + "from aiagents4pharma.talk2knowledgegraphs.utils import kg_utils\n", + "\n", + "import matplotlib.pyplot as plt\n", + "\n", + "# # Set the logging level for httpx to WARNING to suppress INFO messages\n", + "import logging\n", + "logging.getLogger(\"httpx\").setLevel(logging.WARNING)" + ] + }, + { + "cell_type": "code", + "execution_count": 21, + "id": "f724e7f5-1dbf-45cb-a60d-f48180b7adab", + "metadata": {}, + "outputs": [], + "source": [ + "local_dir = '../aiagents4pharma/talk2knowledgegraphs/tests/files/primekg_ibd_pyg_graph.pkl'" + ] + }, + { + "cell_type": "code", + "execution_count": 22, + "id": "a6619d22-6e3e-4167-9231-acfd5a69eeaa", + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "Data(x=[3426, 768], edge_index=[2, 12752], edge_attr=[12752, 768], node_id=[3426], node_name=[3426], node_type=[3426], enriched_node=[3426], key=[12752], head_id=[12752], head_name=[12752], tail_id=[12752], tail_name=[12752], edge_type=[12752], enriched_edge=[12752])" + ] + }, + "execution_count": 22, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "with open(local_dir, 'rb') as file:\n", + " data = pickle.load(file)\n", + "\n", + "data" + ] + }, + { + "cell_type": "code", + "execution_count": 23, + "id": "d62c7c8d-760f-44d3-9c37-ddafbd45fd3e", + "metadata": {}, + "outputs": [], + "source": [ + "G = nx.Graph()\n", + "\n", + "# Add nodes to the graph\n", + "for i in range(len(data['node_id'])):\n", + " G.add_node(\n", + " data['node_id'][i],\n", + " name=data['node_name'][i],\n", + " type=data['node_type'][i],\n", + " enriched_node=data['enriched_node'][i],\n", + " features=data['x'][i].numpy(), # You can add the node features as well\n", + " )\n", + "\n", + "# Add edges to the graph\n", + "for i in range(data['edge_index'].shape[1]): # 12752 edges\n", + " head = data['head_id'][i]\n", + " tail = data['tail_id'][i]\n", + " G.add_edge(\n", + " head,\n", + " tail,\n", + " edge_attr=data['edge_attr'][i].numpy(),\n", + " edge_type=data['edge_type'][i],\n", + " enriched_edge=data['enriched_edge'][i]\n", + " )" + ] + }, + { + "cell_type": "code", + "execution_count": 24, + "id": "53dea1e5-24b8-4705-ac23-0ef1d6f7883e", + "metadata": {}, + "outputs": [ + { + "data": { + "image/png": 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" + ] + }, + "metadata": {}, + "output_type": "display_data" + } + ], + "source": [ + "first_100_nodes = list(G.nodes)[:100]\n", + "\n", + "subgraph = G.subgraph(first_100_nodes)\n", + "\n", + "plt.figure(figsize=(5, 5))\n", + "nx.draw(subgraph, with_labels=True, node_size=50, font_size=8, node_color='skyblue')\n", + "plt.title(\"Subgraph with First 100 Nodes\")\n", + "plt.show()\n" + ] + }, + { + "cell_type": "markdown", + "id": "c3cc2316-c188-45fc-ad72-80e77fcb7396", + "metadata": {}, + "source": [ + "----------" + ] + }, + { + "cell_type": "markdown", + "id": "1e3c0056-0ab0-4551-a158-b2c809d76378", + "metadata": {}, + "source": [ + "### Bert model - transforming from text to tensor" + ] + }, + { + "cell_type": "code", + "execution_count": 25, + "id": "0273b3be-d420-4a2b-b1ca-de0a3e05e8e6", + "metadata": {}, + "outputs": [], + "source": [ + "from transformers import BertTokenizer, BertModel\n", + "from transformers import AutoTokenizer, AutoModel\n", + "import torch" + ] + }, + { + "cell_type": "code", + "execution_count": 26, + "id": "d9c7affa-2558-433d-a3b1-b5dcf31b7ccd", + "metadata": {}, + "outputs": [], + "source": [ + "tokenizer = BertTokenizer.from_pretrained('bert-base-uncased')\n", + "model = BertModel.from_pretrained('bert-base-uncased')\n", + "\n", + "def get_text_embedding(text):\n", + " inputs = tokenizer(text, return_tensors='pt', truncation=True, padding=True, max_length=512)\n", + " outputs = model(**inputs)\n", + " \n", + " return outputs.last_hidden_state.mean(dim=1).detach().numpy() # Shape: (1, hidden_size)\n", + "\n", + "# Example: Get embedding for a species description\n", + "text_description = \"\"\"\n", + " IL1B belongs to gene/protein category. The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. Similarly, IL-1B has been implicated in human osteoarthritis pathogenesis. Patients with severe Coronavirus Disease 2019 (COVID-19) present elevated levels of pro-inflammatory cytokines such as IL-1B in bronchial alveolar lavage fluid samples. The lung damage induced by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to a large extent, a result of the inflammatory response promoted by cytokines such as IL-1B. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2\"\"\"\n", + "text_embedding = get_text_embedding(text_description)\n" + ] + }, + { + "cell_type": "markdown", + "id": "ebbacf39-8e98-49e5-a139-da2493792750", + "metadata": {}, + "source": [ + "### Transform species into vectors" + ] + }, + { + "cell_type": "code", + "execution_count": 29, + "id": "82220b36-281a-4724-88dc-6c4d6fdbf4dd", + "metadata": {}, + "outputs": [], + "source": [ + "species_descriptions = pd.read_csv('species_backgrounds.csv')\n", + "res = []\n", + "for idx, row in species_descriptions.iterrows():\n", + " res += [get_text_embedding(row['background'])]\n", + "species_descriptions['BERT_embedding'] = res" + ] + }, + { + "cell_type": "code", + "execution_count": 30, + "id": "b2084229-ae6e-40a0-a966-919d77cb5ef4", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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idnamebackgroundBERT_embedding
0mwf626e95e_543f_41e4_aad4_c6bf60ab345bIL6Based on the provided context, IL6 (interleuki...[[-0.38310152, 0.14221658, 0.30036777, -0.1971...
1mwbbbce920_e8dd_4320_9386_fc94bfb2fc99sgp130Based on the provided context, the species 'sg...[[-0.39776802, 0.102813065, 0.276282, -0.17234...
2mw810ff751_fa4e_4143_bd50_169b3e325e1esR_IL6_sgp130Based on the provided context, 'sR_IL6_sgp130'...[[-0.41926485, 0.05604683, 0.31495243, -0.0975...
3mw114aa90f_5f5b_4fe8_9406_361c8489b6a1CRPBased on the provided context, CRP, or C-react...[[-0.44731545, 0.21171626, 0.22573717, -0.1713...
4mw30ae63db_6cd3_4b6f_93ad_3350cd360bccsRFrom the provided documents, there is no speci...[[-0.24422143, 0.22741008, 0.3196285, -0.20558...
5mw03db56ac_8dc6_4931_ae82_fef706d2ee3dsR_IL6Based on the provided context and general know...[[-0.38647282, 0.14947572, 0.37386724, -0.2257...
6mwf345ed7a_0622_403c_b816_c8749a2c9dedAbThe context provided from the documents appear...[[-0.35710102, 0.27481169, 0.15268518, -0.2598...
7mw1da111f2_a036_4392_8512_015005bdcbb7Ab_sRThe context provided does not contain specific...[[-0.2979536, 0.22971633, 0.2543159, -0.238324...
8mw9947742a_0e4b_4636_9a4b_b6eef2a8f6acAb_sR_IL6From the context provided, there is no direct ...[[-0.3250525, 0.17176488, 0.2808889, -0.207119...
9CRP_Suppression___CRP Suppression (%)Based on the context provided, \"CRP Suppressio...[[-0.47315472, 0.18459623, 0.24418907, -0.1895...
10CRP____of_baselineCRP (% of baseline)Based on the provided context and general know...[[-0.36008894, 0.18380362, 0.27387857, -0.2149...
11mw80848184_e2dd_47ce_86d7_7a21479342bdgp130Gp130 is an important protein involved in the ...[[-0.35777402, 0.12645116, 0.3562525, -0.23347...
12mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55aR_IL6_gp130The species named 'R_IL6_gp130', provided with...[[-0.3070841, 0.14377351, 0.28311783, -0.18864...
13mw4638f126_8cb8_4021_ab41_6ae195743ba0sR_IL6The species referred to as 'sR_IL6' in the pro...[[-0.41398245, 0.14713271, 0.3669848, -0.26080...
14mw10315fa3_6f13_4618_bda8_a8694bd3c374RBased on the provided context, the document di...[[-0.35146654, 0.103895366, 0.30642122, -0.249...
15mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1IL6IL-6 (Interleukin-6) is a cytokine, a type of ...[[-0.4627117, 0.097201906, 0.3234311, -0.21945...
16mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83R_IL6The context provided from the document does no...[[-0.3934079, 0.2065271, 0.28749886, -0.225543...
17mw0eb6c959_d408_45a0_a450_928b8c5876bbRactiveThe provided context does not specifically men...[[-0.24638735, 0.19071835, 0.17823611, -0.2357...
18mw42054cd7_17af_46da_970c_7f99151906adSTAT3STAT3, or Signal Transducer and Activator of T...[[-0.3920762, 0.21867904, 0.31682876, -0.18099...
19mw39c2e431_fdc3_4964_be29_6ca856620b1bpSTAT3Based on the context provided, pSTAT3 is the p...[[-0.31854075, 0.21612896, 0.36678687, -0.2491...
20mwd5313618_89eb_4c8c_bc82_66f10f966349CRPC-reactive protein (CRP) is a well-known marke...[[-0.4524013, 0.21426782, 0.26746103, -0.18231...
21mw2e464cf3_a09c_4b7c_9f3c_06720016a48esRThe provided context primarily discusses the i...[[-0.25064346, 0.32432884, 0.2525344, -0.19168...
22mw36ea78c1_ed71_4def_96d3_857a442d7195CRPExtracellularThe context provided does not specifically men...[[-0.35434383, 0.24616718, 0.26500684, -0.1196...
23mw147d30ec_478e_4090_b496_128a131d29ebsgp130Based on the provided context, sgp130 appears ...[[-0.37740308, 0.07933396, 0.32603347, -0.1108...
24mwab41493c_6349_45f1_a226_3030cfed0e06sR_IL6_sgp130Based on the context provided and general know...[[-0.37221003, 0.1744852, 0.30792367, -0.15933...
25mwf405687b_7401_44ec_a0d6_4a2b35c13e8aAb_sRBased on the provided context, there is no dir...[[-0.23842902, 0.18786879, 0.2620399, -0.21784...
26mw3667a5e1_02c9_44a0_acb4_b0431faa822dAbThe species denoted as 'Ab' in the context app...[[-0.52765065, 0.27688166, 0.20610718, -0.2776...
27mw772cbf20_3fc1_4800_ae59_77884f1ae333Ab_RBased on the provided context from the documen...[[-0.1863702, 0.36686182, 0.22280839, -0.21697...
28mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cfAb_sR_IL6Based on the context provided, there is no exp...[[-0.3548704, 0.1917099, 0.28657728, -0.262703...
29mw7becb5fe_8da8_4285_a821_0d77ad811b62sR_IL6Based on the context provided, specific inform...[[-0.28405702, 0.10858213, 0.32111079, -0.2300...
30mw8c9107e6_f51d_442d_b2dc_2bfdbb8482cagp130Gp130, also known as glycoprotein 130, is a cr...[[-0.47336444, 0.08036472, 0.37820706, -0.2123...
31mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9R_IL6_gp130Based on the context provided, it appears ther...[[-0.3776276, 0.21458092, 0.3001521, -0.152129...
32mw6cce2109_0e32_4dd9_98ec_41173e8ef07dRactiveThe provided context does not contain direct i...[[-0.2948512, 0.27886307, 0.23734306, -0.22463...
33mw2b255f94_8018_4b99_bde8_918eeac45446STAT3STAT3, or Signal Transducer and Activator of T...[[-0.32530716, 0.24720953, 0.26123106, -0.2493...
34mw48867e93_f170_44e8_ac7a_185b23e1bf3bpSTAT3pSTAT3, or phosphorylated Signal Transducer an...[[-0.37683305, 0.3004347, 0.30100918, -0.21106...
35mw0083d743_836f_4238_a17f_4602193d5bc0geneProductThe context provided does not specifically men...[[-0.30782086, 0.2336929, 0.23015884, -0.16083...
36mwd31f52cc_04e7_40e0_885f_c7b2d9e62215sRBased on the provided context, the species nam...[[-0.3048136, 0.16629891, 0.3336691, -0.178628...
37mw2c9b0499_3325_4394_8af3_bbf653a944a0IL6Based on the provided context, here is the bac...[[-0.4397936, 0.15727538, 0.35291147, -0.22082...
38mwd65b5b39_dc1b_4e77_a999_67277a880e5esgp130sgp130, as described in the context, refers to...[[-0.4935615, 0.10821018, 0.1830138, -0.252587...
39mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3sR_IL6_sgp130The species 'sR_IL6_sgp130' likely refers to a...[[-0.2861055, 0.08323312, 0.34479225, -0.18034...
40mwf7796221_1fea_4274_a93e_c00adbf5778cAbBased on the provided context, there is no dir...[[-0.37095174, 0.32116163, 0.20662963, -0.2790...
41mw5d764bb8_5693_4ac8_9557_f65992cc5eb0Ab_sRThe provided context does not include specific...[[-0.15027289, 0.31890064, 0.17519885, -0.2029...
42mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2Ab_sR_IL6The species \"Ab_sR_IL6\" appears to be involved...[[-0.3795819, 0.24610856, 0.26605865, -0.28016...
43mwbc2f5464_81e5_43fd_8b39_f5a2756af72fAbThe provided documents include information tha...[[-0.46518034, 0.22024783, 0.28029412, -0.2428...
\n", + "
" + ], + "text/plain": [ + " id name \\\n", + "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 \n", + "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130 \n", + "2 mw810ff751_fa4e_4143_bd50_169b3e325e1e sR_IL6_sgp130 \n", + "3 mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 CRP \n", + "4 mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc sR \n", + "5 mw03db56ac_8dc6_4931_ae82_fef706d2ee3d sR_IL6 \n", + "6 mwf345ed7a_0622_403c_b816_c8749a2c9ded Ab \n", + "7 mw1da111f2_a036_4392_8512_015005bdcbb7 Ab_sR \n", + "8 mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac Ab_sR_IL6 \n", + "9 CRP_Suppression___ CRP Suppression (%) \n", + "10 CRP____of_baseline CRP (% of baseline) \n", + "11 mw80848184_e2dd_47ce_86d7_7a21479342bd gp130 \n", + "12 mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a R_IL6_gp130 \n", + "13 mw4638f126_8cb8_4021_ab41_6ae195743ba0 sR_IL6 \n", + "14 mw10315fa3_6f13_4618_bda8_a8694bd3c374 R \n", + "15 mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 IL6 \n", + "16 mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 R_IL6 \n", + "17 mw0eb6c959_d408_45a0_a450_928b8c5876bb Ractive \n", + "18 mw42054cd7_17af_46da_970c_7f99151906ad STAT3 \n", + "19 mw39c2e431_fdc3_4964_be29_6ca856620b1b pSTAT3 \n", + "20 mwd5313618_89eb_4c8c_bc82_66f10f966349 CRP \n", + "21 mw2e464cf3_a09c_4b7c_9f3c_06720016a48e sR \n", + "22 mw36ea78c1_ed71_4def_96d3_857a442d7195 CRPExtracellular \n", + "23 mw147d30ec_478e_4090_b496_128a131d29eb sgp130 \n", + "24 mwab41493c_6349_45f1_a226_3030cfed0e06 sR_IL6_sgp130 \n", + "25 mwf405687b_7401_44ec_a0d6_4a2b35c13e8a Ab_sR \n", + "26 mw3667a5e1_02c9_44a0_acb4_b0431faa822d Ab \n", + "27 mw772cbf20_3fc1_4800_ae59_77884f1ae333 Ab_R \n", + "28 mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf Ab_sR_IL6 \n", + "29 mw7becb5fe_8da8_4285_a821_0d77ad811b62 sR_IL6 \n", + "30 mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca gp130 \n", + "31 mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9 R_IL6_gp130 \n", + "32 mw6cce2109_0e32_4dd9_98ec_41173e8ef07d Ractive \n", + "33 mw2b255f94_8018_4b99_bde8_918eeac45446 STAT3 \n", + "34 mw48867e93_f170_44e8_ac7a_185b23e1bf3b pSTAT3 \n", + "35 mw0083d743_836f_4238_a17f_4602193d5bc0 geneProduct \n", + "36 mwd31f52cc_04e7_40e0_885f_c7b2d9e62215 sR \n", + "37 mw2c9b0499_3325_4394_8af3_bbf653a944a0 IL6 \n", + "38 mwd65b5b39_dc1b_4e77_a999_67277a880e5e sgp130 \n", + "39 mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 sR_IL6_sgp130 \n", + "40 mwf7796221_1fea_4274_a93e_c00adbf5778c Ab \n", + "41 mw5d764bb8_5693_4ac8_9557_f65992cc5eb0 Ab_sR \n", + "42 mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2 Ab_sR_IL6 \n", + "43 mwbc2f5464_81e5_43fd_8b39_f5a2756af72f Ab \n", + "\n", + " background \\\n", + "0 Based on the provided context, IL6 (interleuki... \n", + "1 Based on the provided context, the species 'sg... \n", + "2 Based on the provided context, 'sR_IL6_sgp130'... \n", + "3 Based on the provided context, CRP, or C-react... \n", + "4 From the provided documents, there is no speci... \n", + "5 Based on the provided context and general know... \n", + "6 The context provided from the documents appear... \n", + "7 The context provided does not contain specific... \n", + "8 From the context provided, there is no direct ... \n", + "9 Based on the context provided, \"CRP Suppressio... \n", + "10 Based on the provided context and general know... \n", + "11 Gp130 is an important protein involved in the ... \n", + "12 The species named 'R_IL6_gp130', provided with... \n", + "13 The species referred to as 'sR_IL6' in the pro... \n", + "14 Based on the provided context, the document di... \n", + "15 IL-6 (Interleukin-6) is a cytokine, a type of ... \n", + "16 The context provided from the document does no... \n", + "17 The provided context does not specifically men... \n", + "18 STAT3, or Signal Transducer and Activator of T... \n", + "19 Based on the context provided, pSTAT3 is the p... \n", + "20 C-reactive protein (CRP) is a well-known marke... \n", + "21 The provided context primarily discusses the i... \n", + "22 The context provided does not specifically men... \n", + "23 Based on the provided context, sgp130 appears ... \n", + "24 Based on the context provided and general know... \n", + "25 Based on the provided context, there is no dir... \n", + "26 The species denoted as 'Ab' in the context app... \n", + "27 Based on the provided context from the documen... \n", + "28 Based on the context provided, there is no exp... \n", + "29 Based on the context provided, specific inform... \n", + "30 Gp130, also known as glycoprotein 130, is a cr... \n", + "31 Based on the context provided, it appears ther... \n", + "32 The provided context does not contain direct i... \n", + "33 STAT3, or Signal Transducer and Activator of T... \n", + "34 pSTAT3, or phosphorylated Signal Transducer an... \n", + "35 The context provided does not specifically men... \n", + "36 Based on the provided context, the species nam... \n", + "37 Based on the provided context, here is the bac... \n", + "38 sgp130, as described in the context, refers to... \n", + "39 The species 'sR_IL6_sgp130' likely refers to a... \n", + "40 Based on the provided context, there is no dir... \n", + "41 The provided context does not include specific... \n", + "42 The species \"Ab_sR_IL6\" appears to be involved... \n", + "43 The provided documents include information tha... \n", + "\n", + " BERT_embedding \n", + "0 [[-0.38310152, 0.14221658, 0.30036777, -0.1971... \n", + "1 [[-0.39776802, 0.102813065, 0.276282, -0.17234... \n", + "2 [[-0.41926485, 0.05604683, 0.31495243, -0.0975... \n", + "3 [[-0.44731545, 0.21171626, 0.22573717, -0.1713... \n", + "4 [[-0.24422143, 0.22741008, 0.3196285, -0.20558... \n", + "5 [[-0.38647282, 0.14947572, 0.37386724, -0.2257... \n", + "6 [[-0.35710102, 0.27481169, 0.15268518, -0.2598... \n", + "7 [[-0.2979536, 0.22971633, 0.2543159, -0.238324... \n", + "8 [[-0.3250525, 0.17176488, 0.2808889, -0.207119... \n", + "9 [[-0.47315472, 0.18459623, 0.24418907, -0.1895... \n", + "10 [[-0.36008894, 0.18380362, 0.27387857, -0.2149... \n", + "11 [[-0.35777402, 0.12645116, 0.3562525, -0.23347... \n", + "12 [[-0.3070841, 0.14377351, 0.28311783, -0.18864... \n", + "13 [[-0.41398245, 0.14713271, 0.3669848, -0.26080... \n", + "14 [[-0.35146654, 0.103895366, 0.30642122, -0.249... \n", + "15 [[-0.4627117, 0.097201906, 0.3234311, -0.21945... \n", + "16 [[-0.3934079, 0.2065271, 0.28749886, -0.225543... \n", + "17 [[-0.24638735, 0.19071835, 0.17823611, -0.2357... \n", + "18 [[-0.3920762, 0.21867904, 0.31682876, -0.18099... \n", + "19 [[-0.31854075, 0.21612896, 0.36678687, -0.2491... \n", + "20 [[-0.4524013, 0.21426782, 0.26746103, -0.18231... \n", + "21 [[-0.25064346, 0.32432884, 0.2525344, -0.19168... \n", + "22 [[-0.35434383, 0.24616718, 0.26500684, -0.1196... \n", + "23 [[-0.37740308, 0.07933396, 0.32603347, -0.1108... \n", + "24 [[-0.37221003, 0.1744852, 0.30792367, -0.15933... \n", + "25 [[-0.23842902, 0.18786879, 0.2620399, -0.21784... \n", + "26 [[-0.52765065, 0.27688166, 0.20610718, -0.2776... \n", + "27 [[-0.1863702, 0.36686182, 0.22280839, -0.21697... \n", + "28 [[-0.3548704, 0.1917099, 0.28657728, -0.262703... \n", + "29 [[-0.28405702, 0.10858213, 0.32111079, -0.2300... \n", + "30 [[-0.47336444, 0.08036472, 0.37820706, -0.2123... \n", + "31 [[-0.3776276, 0.21458092, 0.3001521, -0.152129... \n", + "32 [[-0.2948512, 0.27886307, 0.23734306, -0.22463... \n", + "33 [[-0.32530716, 0.24720953, 0.26123106, -0.2493... \n", + "34 [[-0.37683305, 0.3004347, 0.30100918, -0.21106... \n", + "35 [[-0.30782086, 0.2336929, 0.23015884, -0.16083... \n", + "36 [[-0.3048136, 0.16629891, 0.3336691, -0.178628... \n", + "37 [[-0.4397936, 0.15727538, 0.35291147, -0.22082... \n", + "38 [[-0.4935615, 0.10821018, 0.1830138, -0.252587... \n", + "39 [[-0.2861055, 0.08323312, 0.34479225, -0.18034... \n", + "40 [[-0.37095174, 0.32116163, 0.20662963, -0.2790... \n", + "41 [[-0.15027289, 0.31890064, 0.17519885, -0.2029... \n", + "42 [[-0.3795819, 0.24610856, 0.26605865, -0.28016... \n", + "43 [[-0.46518034, 0.22024783, 0.28029412, -0.2428... " + ] + }, + "execution_count": 30, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "species_descriptions" + ] + }, + { + "cell_type": "markdown", + "id": "764bdd6c-1e62-4a42-b97d-d43644ba82d9", + "metadata": {}, + "source": [ + "### Graph behaviour" + ] + }, + { + "cell_type": "markdown", + "id": "b0e26fcb-9506-4c2e-9e9f-dfe14efa3f23", + "metadata": {}, + "source": [ + "We pass each enriched node text through the BERT model to obtain an embedding" + ] + }, + { + "cell_type": "code", + "execution_count": 31, + "id": "e6c0fe91-e158-4fb3-aa91-d96e54ec5f88", + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "0 / 3426\n", + "1 / 3426\n", + "2 / 3426\n", + "3 / 3426\n", + "4 / 3426\n", + "5 / 3426\n", + "6 / 3426\n", + "7 / 3426\n", + "8 / 3426\n", + "9 / 3426\n", + "10 / 3426\n", + "11 / 3426\n", + "12 / 3426\n", + "13 / 3426\n", + "14 / 3426\n", + "15 / 3426\n", + "16 / 3426\n", + "17 / 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"\n", + "for node_idx in range(total_len):\n", + " node = nodes_list[node_idx]\n", + " print(f\"{node_idx} / {total_len}\")\n", + " \n", + " try:\n", + " if 'enriched_node' in G.nodes[node]:\n", + " text = G.nodes[node]['enriched_node']\n", + " G.nodes[node]['BERT_embedding'] = get_text_embedding(text)\n", + " else:\n", + " print(f\"Warning: 'enriched_node' not found for node {node}\")\n", + " except Exception as e:\n", + " print(f\"Error processing node {node}: {e}\")\n", + " \n", + " if node_idx % batch_size == 0 and node_idx != 0:\n", + " gc.collect() # Force garbage collection to free memory\n" + ] + }, + { + "cell_type": "markdown", + "id": "750eb21d-f40c-413e-8982-6ce0ec41d21e", + "metadata": {}, + "source": [ + "### We add neighbor embeddings" + ] + }, + { + "cell_type": "code", + "execution_count": 32, + "id": "4c61048d-ca2e-407f-b72c-828852e7302f", + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "0\n", + 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seen_nodes.update(nodes_n_hops_away)\n", + " \n", + " # Add the embeddings for these neighbors, weighted by proportion\n", + " for neighbor_idx in nodes_n_hops_away:\n", + " neighbor_node = G.nodes[neighbor_idx]\n", + " neighbor_embedding += neighbor_node['BERT_embedding'] * proportions[prop_idx]\n", + " weight += proportions[prop_idx] # Add the weight of the current hop level\n", + "\n", + " # Normalize the final embedding by the total weight\n", + " neighbor_embedding = neighbor_embedding / weight\n", + " node['FINAL_embedding'] = (embedding + neighbor_embedding * .25) / (1 + 0.25)\n", + " #print(f\"Final embedding for node {node_name}: {node['FINAL_embedding']}\")\n" + ] + }, + { + "cell_type": "markdown", + "id": "4d2003b5-52c4-4f18-a30e-54ee4a442a99", + "metadata": {}, + "source": [ + "### Obtain most similar embedding" + ] + }, + { + "cell_type": "code", + "execution_count": 33, + "id": "1b522cd8-4e38-4148-94b1-de3386762a70", + "metadata": {}, + "outputs": [], + "source": [ + "def compare_species_in_graph(text_embedding, G, nodes_list):\n", + " best_node = None\n", + " best_sim = -1\n", + " \n", + " for node_name in nodes_list:\n", + " curr_emb = G.nodes[node_name]['FINAL_embedding']\n", + " \n", + " curr_emb = curr_emb.flatten()\n", + " text_embedding = text_embedding.flatten()\n", + " \n", + " sim = np.dot(curr_emb, text_embedding) / (np.linalg.norm(curr_emb) * np.linalg.norm(text_embedding))\n", + " #sim = np.linalg.norm(curr_emb - text_embedding)\n", + " if ((best_node is None) | (sim > best_sim)):\n", + " best_node = node_name\n", + " best_sim = sim\n", + " return best_node, best_sim" + ] + }, + { + "cell_type": "code", + "execution_count": 34, + "id": "143fede2-c942-4eac-a544-277f88b20479", + "metadata": { + "scrolled": true + }, + "outputs": [], + "source": [ + "res = []\n", + "for idx, row in species_descriptions.iterrows():\n", + " best_node, best_sim = compare_species_in_graph(row['BERT_embedding'], G, nodes_list)\n", + " res += [best_node]\n", + "\n", + "species_descriptions['best_node'] = res" + ] + }, + { + "cell_type": "code", + "execution_count": 35, + "id": "27bee18b-e76b-43f1-9bcd-7866ffc9d394", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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idnamebackgroundBERT_embeddingbest_node
0mwf626e95e_543f_41e4_aad4_c6bf60ab345bIL6Based on the provided context, IL6 (interleuki...[[-0.38310152, 0.14221658, 0.30036777, -0.1971...CLEC7A (Dectin-1) signaling_(62768)
1mwbbbce920_e8dd_4320_9386_fc94bfb2fc99sgp130Based on the provided context, the species 'sg...[[-0.39776802, 0.102813065, 0.276282, -0.17234...Interleukin-2 signaling_(128499)
2mw810ff751_fa4e_4143_bd50_169b3e325e1esR_IL6_sgp130Based on the provided context, 'sR_IL6_sgp130'...[[-0.41926485, 0.05604683, 0.31495243, -0.0975...IRAK2 mediated activation of TAK1 complex upon...
3mw114aa90f_5f5b_4fe8_9406_361c8489b6a1CRPBased on the provided context, CRP, or C-react...[[-0.44731545, 0.21171626, 0.22573717, -0.1713...Immunoregulatory interactions between a Lympho...
4mw30ae63db_6cd3_4b6f_93ad_3350cd360bccsRFrom the provided documents, there is no speci...[[-0.24422143, 0.22741008, 0.3196285, -0.20558...Regulation of Complement cascade_(127866)
5mw03db56ac_8dc6_4931_ae82_fef706d2ee3dsR_IL6Based on the provided context and general know...[[-0.38647282, 0.14947572, 0.37386724, -0.2257...Interleukin-6 signaling_(128814)
6mwf345ed7a_0622_403c_b816_c8749a2c9dedAbThe context provided from the documents appear...[[-0.35710102, 0.27481169, 0.15268518, -0.2598...Interleukin-2 signaling_(128499)
7mw1da111f2_a036_4392_8512_015005bdcbb7Ab_sRThe context provided does not contain specific...[[-0.2979536, 0.22971633, 0.2543159, -0.238324...Cytoprotection by HMOX1_(63064)
8mw9947742a_0e4b_4636_9a4b_b6eef2a8f6acAb_sR_IL6From the context provided, there is no direct ...[[-0.3250525, 0.17176488, 0.2808889, -0.207119...Interleukin-2 signaling_(128499)
9CRP_Suppression___CRP Suppression (%)Based on the context provided, \"CRP Suppressio...[[-0.47315472, 0.18459623, 0.24418907, -0.1895...Cannabidiol_(14656)
10CRP____of_baselineCRP (% of baseline)Based on the provided context and general know...[[-0.36008894, 0.18380362, 0.27387857, -0.2149...Tezacaftor_(15045)
11mw80848184_e2dd_47ce_86d7_7a21479342bdgp130Gp130 is an important protein involved in the ...[[-0.35777402, 0.12645116, 0.3562525, -0.23347...Interleukin-12 signaling_(62987)
12mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55aR_IL6_gp130The species named 'R_IL6_gp130', provided with...[[-0.3070841, 0.14377351, 0.28311783, -0.18864...CD209 (DC-SIGN) signaling_(128715)
13mw4638f126_8cb8_4021_ab41_6ae195743ba0sR_IL6The species referred to as 'sR_IL6' in the pro...[[-0.41398245, 0.14713271, 0.3669848, -0.26080...Interleukin-2 signaling_(128499)
14mw10315fa3_6f13_4618_bda8_a8694bd3c374RBased on the provided context, the document di...[[-0.35146654, 0.103895366, 0.30642122, -0.249...Interleukin-2 signaling_(128499)
15mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1IL6IL-6 (Interleukin-6) is a cytokine, a type of ...[[-0.4627117, 0.097201906, 0.3234311, -0.21945...Zanubrutinib_(15748)
16mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83R_IL6The context provided from the document does no...[[-0.3934079, 0.2065271, 0.28749886, -0.225543...CLEC7A (Dectin-1) signaling_(62768)
17mw0eb6c959_d408_45a0_a450_928b8c5876bbRactiveThe provided context does not specifically men...[[-0.24638735, 0.19071835, 0.17823611, -0.2357...Cannabidiol_(14656)
18mw42054cd7_17af_46da_970c_7f99151906adSTAT3STAT3, or Signal Transducer and Activator of T...[[-0.3920762, 0.21867904, 0.31682876, -0.18099...MyD88:MAL(TIRAP) cascade initiated on plasma m...
19mw39c2e431_fdc3_4964_be29_6ca856620b1bpSTAT3Based on the context provided, pSTAT3 is the p...[[-0.31854075, 0.21612896, 0.36678687, -0.2491...NOD1/2 Signaling Pathway_(127908)
20mwd5313618_89eb_4c8c_bc82_66f10f966349CRPC-reactive protein (CRP) is a well-known marke...[[-0.4524013, 0.21426782, 0.26746103, -0.18231...Cytoprotection by HMOX1_(63064)
21mw2e464cf3_a09c_4b7c_9f3c_06720016a48esRThe provided context primarily discusses the i...[[-0.25064346, 0.32432884, 0.2525344, -0.19168...Interleukin-2 signaling_(128499)
22mw36ea78c1_ed71_4def_96d3_857a442d7195CRPExtracellularThe context provided does not specifically men...[[-0.35434383, 0.24616718, 0.26500684, -0.1196...Immunoregulatory interactions between a Lympho...
23mw147d30ec_478e_4090_b496_128a131d29ebsgp130Based on the provided context, sgp130 appears ...[[-0.37740308, 0.07933396, 0.32603347, -0.1108...Interleukin-2 signaling_(128499)
24mwab41493c_6349_45f1_a226_3030cfed0e06sR_IL6_sgp130Based on the context provided and general know...[[-0.37221003, 0.1744852, 0.30792367, -0.15933...Interleukin-2 signaling_(128499)
25mwf405687b_7401_44ec_a0d6_4a2b35c13e8aAb_sRBased on the provided context, there is no dir...[[-0.23842902, 0.18786879, 0.2620399, -0.21784...CD209 (DC-SIGN) signaling_(128715)
26mw3667a5e1_02c9_44a0_acb4_b0431faa822dAbThe species denoted as 'Ab' in the context app...[[-0.52765065, 0.27688166, 0.20610718, -0.2776...Cytoprotection by HMOX1_(63064)
27mw772cbf20_3fc1_4800_ae59_77884f1ae333Ab_RBased on the provided context from the documen...[[-0.1863702, 0.36686182, 0.22280839, -0.21697...Immunoregulatory interactions between a Lympho...
28mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cfAb_sR_IL6Based on the context provided, there is no exp...[[-0.3548704, 0.1917099, 0.28657728, -0.262703...IRAK2 mediated activation of TAK1 complex upon...
29mw7becb5fe_8da8_4285_a821_0d77ad811b62sR_IL6Based on the context provided, specific inform...[[-0.28405702, 0.10858213, 0.32111079, -0.2300...Interleukin-2 signaling_(128499)
30mw8c9107e6_f51d_442d_b2dc_2bfdbb8482cagp130Gp130, also known as glycoprotein 130, is a cr...[[-0.47336444, 0.08036472, 0.37820706, -0.2123...Interleukin-6 signaling_(128814)
31mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9R_IL6_gp130Based on the context provided, it appears ther...[[-0.3776276, 0.21458092, 0.3001521, -0.152129...Interleukin-6 signaling_(128814)
32mw6cce2109_0e32_4dd9_98ec_41173e8ef07dRactiveThe provided context does not contain direct i...[[-0.2948512, 0.27886307, 0.23734306, -0.22463...Regulation of TLR by endogenous ligand_(127918)
33mw2b255f94_8018_4b99_bde8_918eeac45446STAT3STAT3, or Signal Transducer and Activator of T...[[-0.32530716, 0.24720953, 0.26123106, -0.2493...Growth hormone receptor signaling_(127694)
34mw48867e93_f170_44e8_ac7a_185b23e1bf3bpSTAT3pSTAT3, or phosphorylated Signal Transducer an...[[-0.37683305, 0.3004347, 0.30100918, -0.21106...Signaling by MST1_(129128)
35mw0083d743_836f_4238_a17f_4602193d5bc0geneProductThe context provided does not specifically men...[[-0.30782086, 0.2336929, 0.23015884, -0.16083...Interleukin-1 processing_(128470)
36mwd31f52cc_04e7_40e0_885f_c7b2d9e62215sRBased on the provided context, the species nam...[[-0.3048136, 0.16629891, 0.3336691, -0.178628...Interleukin-2 signaling_(128499)
37mw2c9b0499_3325_4394_8af3_bbf653a944a0IL6Based on the provided context, here is the bac...[[-0.4397936, 0.15727538, 0.35291147, -0.22082...Zanubrutinib_(15748)
38mwd65b5b39_dc1b_4e77_a999_67277a880e5esgp130sgp130, as described in the context, refers to...[[-0.4935615, 0.10821018, 0.1830138, -0.252587...Cytoprotection by HMOX1_(63064)
39mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3sR_IL6_sgp130The species 'sR_IL6_sgp130' likely refers to a...[[-0.2861055, 0.08323312, 0.34479225, -0.18034...Interleukin-6 signaling_(128814)
40mwf7796221_1fea_4274_a93e_c00adbf5778cAbBased on the provided context, there is no dir...[[-0.37095174, 0.32116163, 0.20662963, -0.2790...Canakinumab_(18416)
41mw5d764bb8_5693_4ac8_9557_f65992cc5eb0Ab_sRThe provided context does not include specific...[[-0.15027289, 0.31890064, 0.17519885, -0.2029...Regulation of Complement cascade_(127866)
42mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2Ab_sR_IL6The species \"Ab_sR_IL6\" appears to be involved...[[-0.3795819, 0.24610856, 0.26605865, -0.28016...Interleukin-2 signaling_(128499)
43mwbc2f5464_81e5_43fd_8b39_f5a2756af72fAbThe provided documents include information tha...[[-0.46518034, 0.22024783, 0.28029412, -0.2428...Sarilumab_(15662)
\n", + "
" + ], + "text/plain": [ + " id name \\\n", + "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 \n", + "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130 \n", + "2 mw810ff751_fa4e_4143_bd50_169b3e325e1e sR_IL6_sgp130 \n", + "3 mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 CRP \n", + "4 mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc sR \n", + "5 mw03db56ac_8dc6_4931_ae82_fef706d2ee3d sR_IL6 \n", + "6 mwf345ed7a_0622_403c_b816_c8749a2c9ded Ab \n", + "7 mw1da111f2_a036_4392_8512_015005bdcbb7 Ab_sR \n", + "8 mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac Ab_sR_IL6 \n", + "9 CRP_Suppression___ CRP Suppression (%) \n", + "10 CRP____of_baseline CRP (% of baseline) \n", + "11 mw80848184_e2dd_47ce_86d7_7a21479342bd gp130 \n", + "12 mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a R_IL6_gp130 \n", + "13 mw4638f126_8cb8_4021_ab41_6ae195743ba0 sR_IL6 \n", + "14 mw10315fa3_6f13_4618_bda8_a8694bd3c374 R \n", + "15 mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 IL6 \n", + "16 mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 R_IL6 \n", + "17 mw0eb6c959_d408_45a0_a450_928b8c5876bb Ractive \n", + "18 mw42054cd7_17af_46da_970c_7f99151906ad STAT3 \n", + "19 mw39c2e431_fdc3_4964_be29_6ca856620b1b pSTAT3 \n", + "20 mwd5313618_89eb_4c8c_bc82_66f10f966349 CRP \n", + "21 mw2e464cf3_a09c_4b7c_9f3c_06720016a48e sR \n", + "22 mw36ea78c1_ed71_4def_96d3_857a442d7195 CRPExtracellular \n", + "23 mw147d30ec_478e_4090_b496_128a131d29eb sgp130 \n", + "24 mwab41493c_6349_45f1_a226_3030cfed0e06 sR_IL6_sgp130 \n", + "25 mwf405687b_7401_44ec_a0d6_4a2b35c13e8a Ab_sR \n", + "26 mw3667a5e1_02c9_44a0_acb4_b0431faa822d Ab \n", + "27 mw772cbf20_3fc1_4800_ae59_77884f1ae333 Ab_R \n", + "28 mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf Ab_sR_IL6 \n", + "29 mw7becb5fe_8da8_4285_a821_0d77ad811b62 sR_IL6 \n", + "30 mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca gp130 \n", + "31 mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9 R_IL6_gp130 \n", + "32 mw6cce2109_0e32_4dd9_98ec_41173e8ef07d Ractive \n", + "33 mw2b255f94_8018_4b99_bde8_918eeac45446 STAT3 \n", + "34 mw48867e93_f170_44e8_ac7a_185b23e1bf3b pSTAT3 \n", + "35 mw0083d743_836f_4238_a17f_4602193d5bc0 geneProduct \n", + "36 mwd31f52cc_04e7_40e0_885f_c7b2d9e62215 sR \n", + "37 mw2c9b0499_3325_4394_8af3_bbf653a944a0 IL6 \n", + "38 mwd65b5b39_dc1b_4e77_a999_67277a880e5e sgp130 \n", + "39 mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 sR_IL6_sgp130 \n", + "40 mwf7796221_1fea_4274_a93e_c00adbf5778c Ab \n", + "41 mw5d764bb8_5693_4ac8_9557_f65992cc5eb0 Ab_sR \n", + "42 mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2 Ab_sR_IL6 \n", + "43 mwbc2f5464_81e5_43fd_8b39_f5a2756af72f Ab \n", + "\n", + " background \\\n", + "0 Based on the provided context, IL6 (interleuki... \n", + "1 Based on the provided context, the species 'sg... \n", + "2 Based on the provided context, 'sR_IL6_sgp130'... \n", + "3 Based on the provided context, CRP, or C-react... \n", + "4 From the provided documents, there is no speci... \n", + "5 Based on the provided context and general know... \n", + "6 The context provided from the documents appear... \n", + "7 The context provided does not contain specific... \n", + "8 From the context provided, there is no direct ... \n", + "9 Based on the context provided, \"CRP Suppressio... \n", + "10 Based on the provided context and general know... \n", + "11 Gp130 is an important protein involved in the ... \n", + "12 The species named 'R_IL6_gp130', provided with... \n", + "13 The species referred to as 'sR_IL6' in the pro... \n", + "14 Based on the provided context, the document di... \n", + "15 IL-6 (Interleukin-6) is a cytokine, a type of ... \n", + "16 The context provided from the document does no... \n", + "17 The provided context does not specifically men... \n", + "18 STAT3, or Signal Transducer and Activator of T... \n", + "19 Based on the context provided, pSTAT3 is the p... \n", + "20 C-reactive protein (CRP) is a well-known marke... \n", + "21 The provided context primarily discusses the i... \n", + "22 The context provided does not specifically men... \n", + "23 Based on the provided context, sgp130 appears ... \n", + "24 Based on the context provided and general know... \n", + "25 Based on the provided context, there is no dir... \n", + "26 The species denoted as 'Ab' in the context app... \n", + "27 Based on the provided context from the documen... \n", + "28 Based on the context provided, there is no exp... \n", + "29 Based on the context provided, specific inform... \n", + "30 Gp130, also known as glycoprotein 130, is a cr... \n", + "31 Based on the context provided, it appears ther... \n", + "32 The provided context does not contain direct i... \n", + "33 STAT3, or Signal Transducer and Activator of T... \n", + "34 pSTAT3, or phosphorylated Signal Transducer an... \n", + "35 The context provided does not specifically men... \n", + "36 Based on the provided context, the species nam... \n", + "37 Based on the provided context, here is the bac... \n", + "38 sgp130, as described in the context, refers to... \n", + "39 The species 'sR_IL6_sgp130' likely refers to a... \n", + "40 Based on the provided context, there is no dir... \n", + "41 The provided context does not include specific... \n", + "42 The species \"Ab_sR_IL6\" appears to be involved... \n", + "43 The provided documents include information tha... \n", + "\n", + " BERT_embedding \\\n", + "0 [[-0.38310152, 0.14221658, 0.30036777, -0.1971... \n", + "1 [[-0.39776802, 0.102813065, 0.276282, -0.17234... \n", + "2 [[-0.41926485, 0.05604683, 0.31495243, -0.0975... \n", + "3 [[-0.44731545, 0.21171626, 0.22573717, -0.1713... \n", + "4 [[-0.24422143, 0.22741008, 0.3196285, -0.20558... \n", + "5 [[-0.38647282, 0.14947572, 0.37386724, -0.2257... \n", + "6 [[-0.35710102, 0.27481169, 0.15268518, -0.2598... \n", + "7 [[-0.2979536, 0.22971633, 0.2543159, -0.238324... \n", + "8 [[-0.3250525, 0.17176488, 0.2808889, -0.207119... \n", + "9 [[-0.47315472, 0.18459623, 0.24418907, -0.1895... \n", + "10 [[-0.36008894, 0.18380362, 0.27387857, -0.2149... \n", + "11 [[-0.35777402, 0.12645116, 0.3562525, -0.23347... \n", + "12 [[-0.3070841, 0.14377351, 0.28311783, -0.18864... \n", + "13 [[-0.41398245, 0.14713271, 0.3669848, -0.26080... \n", + "14 [[-0.35146654, 0.103895366, 0.30642122, -0.249... \n", + "15 [[-0.4627117, 0.097201906, 0.3234311, -0.21945... \n", + "16 [[-0.3934079, 0.2065271, 0.28749886, -0.225543... \n", + "17 [[-0.24638735, 0.19071835, 0.17823611, -0.2357... \n", + "18 [[-0.3920762, 0.21867904, 0.31682876, -0.18099... \n", + "19 [[-0.31854075, 0.21612896, 0.36678687, -0.2491... \n", + "20 [[-0.4524013, 0.21426782, 0.26746103, -0.18231... \n", + "21 [[-0.25064346, 0.32432884, 0.2525344, -0.19168... \n", + "22 [[-0.35434383, 0.24616718, 0.26500684, -0.1196... \n", + "23 [[-0.37740308, 0.07933396, 0.32603347, -0.1108... \n", + "24 [[-0.37221003, 0.1744852, 0.30792367, -0.15933... \n", + "25 [[-0.23842902, 0.18786879, 0.2620399, -0.21784... \n", + "26 [[-0.52765065, 0.27688166, 0.20610718, -0.2776... \n", + "27 [[-0.1863702, 0.36686182, 0.22280839, -0.21697... \n", + "28 [[-0.3548704, 0.1917099, 0.28657728, -0.262703... \n", + "29 [[-0.28405702, 0.10858213, 0.32111079, -0.2300... \n", + "30 [[-0.47336444, 0.08036472, 0.37820706, -0.2123... \n", + "31 [[-0.3776276, 0.21458092, 0.3001521, -0.152129... \n", + "32 [[-0.2948512, 0.27886307, 0.23734306, -0.22463... \n", + "33 [[-0.32530716, 0.24720953, 0.26123106, -0.2493... \n", + "34 [[-0.37683305, 0.3004347, 0.30100918, -0.21106... \n", + "35 [[-0.30782086, 0.2336929, 0.23015884, -0.16083... \n", + "36 [[-0.3048136, 0.16629891, 0.3336691, -0.178628... \n", + "37 [[-0.4397936, 0.15727538, 0.35291147, -0.22082... \n", + "38 [[-0.4935615, 0.10821018, 0.1830138, -0.252587... \n", + "39 [[-0.2861055, 0.08323312, 0.34479225, -0.18034... \n", + "40 [[-0.37095174, 0.32116163, 0.20662963, -0.2790... \n", + "41 [[-0.15027289, 0.31890064, 0.17519885, -0.2029... \n", + "42 [[-0.3795819, 0.24610856, 0.26605865, -0.28016... \n", + "43 [[-0.46518034, 0.22024783, 0.28029412, -0.2428... \n", + "\n", + " best_node \n", + "0 CLEC7A (Dectin-1) signaling_(62768) \n", + "1 Interleukin-2 signaling_(128499) \n", + "2 IRAK2 mediated activation of TAK1 complex upon... \n", + "3 Immunoregulatory interactions between a Lympho... \n", + "4 Regulation of Complement cascade_(127866) \n", + "5 Interleukin-6 signaling_(128814) \n", + "6 Interleukin-2 signaling_(128499) \n", + "7 Cytoprotection by HMOX1_(63064) \n", + "8 Interleukin-2 signaling_(128499) \n", + "9 Cannabidiol_(14656) \n", + "10 Tezacaftor_(15045) \n", + "11 Interleukin-12 signaling_(62987) \n", + "12 CD209 (DC-SIGN) signaling_(128715) \n", + "13 Interleukin-2 signaling_(128499) \n", + "14 Interleukin-2 signaling_(128499) \n", + "15 Zanubrutinib_(15748) \n", + "16 CLEC7A (Dectin-1) signaling_(62768) \n", + "17 Cannabidiol_(14656) \n", + "18 MyD88:MAL(TIRAP) cascade initiated on plasma m... \n", + "19 NOD1/2 Signaling Pathway_(127908) \n", + "20 Cytoprotection by HMOX1_(63064) \n", + "21 Interleukin-2 signaling_(128499) \n", + "22 Immunoregulatory interactions between a Lympho... \n", + "23 Interleukin-2 signaling_(128499) \n", + "24 Interleukin-2 signaling_(128499) \n", + "25 CD209 (DC-SIGN) signaling_(128715) \n", + "26 Cytoprotection by HMOX1_(63064) \n", + "27 Immunoregulatory interactions between a Lympho... \n", + "28 IRAK2 mediated activation of TAK1 complex upon... \n", + "29 Interleukin-2 signaling_(128499) \n", + "30 Interleukin-6 signaling_(128814) \n", + "31 Interleukin-6 signaling_(128814) \n", + "32 Regulation of TLR by endogenous ligand_(127918) \n", + "33 Growth hormone receptor signaling_(127694) \n", + "34 Signaling by MST1_(129128) \n", + "35 Interleukin-1 processing_(128470) \n", + "36 Interleukin-2 signaling_(128499) \n", + "37 Zanubrutinib_(15748) \n", + "38 Cytoprotection by HMOX1_(63064) \n", + "39 Interleukin-6 signaling_(128814) \n", + "40 Canakinumab_(18416) \n", + "41 Regulation of Complement cascade_(127866) \n", + "42 Interleukin-2 signaling_(128499) \n", + "43 Sarilumab_(15662) " + ] + }, + "execution_count": 35, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "species_descriptions" + ] + }, + { + "cell_type": "markdown", + "id": "a6a2d263-446c-4c38-9d02-21daa9624c02", + "metadata": {}, + "source": [ + "-----------------" + ] + }, + { + "cell_type": "code", + "execution_count": 15, + "id": "98e737b2-b175-463b-9506-d4294c4138ce", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Loading nodes of PrimeKG dataset ...\n", + "../../data/primekg/primekg_nodes.tsv.gz already exists. Loading the data from the local directory.\n", + "Loading edges of PrimeKG dataset ...\n", + "../../data/primekg/primekg_edges.tsv.gz already exists. Loading the data from the local directory.\n" + ] + } + ], + "source": [ + "# Define primekg data by providing a local directory where the data is stored\n", + "primekg_data = PrimeKG(local_dir=\"../../data/primekg/\")\n", + "\n", + "# Invoke a method to load the data\n", + "primekg_data.load_data()\n", + "\n", + "# Get primekg_nodes and primekg_edges\n", + "primekg_nodes = primekg_data.get_nodes()\n", + "primekg_edges = primekg_data.get_edges()" + ] + }, + { + "cell_type": "code", + "execution_count": 16, + "id": "96db0b07-74df-4ff6-b851-a6f273d828ae", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "R-HSA-9707564\n" + ] + } + ], + "source": [ + "relevant_node_name = G.nodes[best_node]['name'].lower()\n", + "query_str = f'node_name_lower.eq(\"{relevant_node_name}\")'\n", + "\n", + "# Get the nodes related to IBD\n", + "nodes_df = primekg_nodes.copy()\n", + "nodes_df[\"node_name_lower\"] = nodes_df.node_name.apply(lambda x: x.lower())\n", + "nodes_df = nodes_df.query(query_str, engine='python')\n", + "\n", + "code = nodes_df.iloc[0]['node_id']\n", + "\n", + "print(code)" + ] + }, + { + "cell_type": "code", + "execution_count": 38, + "id": "66b3300b-d0c5-439d-8afd-1909892b37be", + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "False" + ] + }, + "execution_count": 38, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "'STAT3' in nodes_list" + ] + } + ], + "metadata": { + "kernelspec": { + "display_name": "Python (myenv)", + "language": "python", + "name": "myenv" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.11.11" + } + }, + "nbformat": 4, + "nbformat_minor": 5 +} diff --git a/notebook/species_backgrounds.csv b/notebook/species_backgrounds.csv index 15e043e9..f9e0d87d 100644 --- a/notebook/species_backgrounds.csv +++ b/notebook/species_backgrounds.csv @@ -1,19 +1,655 @@ -id,name,original_name,compartment,background -mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Interleukin-6 (IL-6) is a cytokine that plays a significant role in the immune system and has been implicated in various inflammatory diseases, including Crohn’s disease. In the context of Crohn's disease, IL-6 is identified as an important factor contributing to enhanced T-cell survival and resistance to apoptosis in the lamina propria, which is a part of the intestinal mucosa. This activity is associated with increased chemokine secretion, which can exacerbate the inflammatory response. +id,name,background +mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,"Based on the provided context, IL6 (interleukin-6) is a cytokine that plays a vital role in immune regulation, particularly in the context of inflammatory diseases like Crohn's disease. Here is a summary of its background information: -IL-6 signaling can occur via two pathways: the classical signaling pathway and the trans-signaling pathway. The classical pathway is mediated by the membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor, forming a complex that ultimately leads to the activation of Janus kinase (Jak) proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation. The trans-signaling pathway is particularly relevant in disease states because it allows IL-6 to exert effects even in cells that do not express the membrane-bound IL-6Rα. +1. **Biological Function:** + - IL6 is a critical mediator in the immune system, known for its involvement in inflammation and immune responses. + - It contributes to the survival of T-cells and resistance to apoptosis, especially in the lamina propria, a tissue region in the gut affected in Crohn’s disease. -In therapeutic contexts, antibodies targeting IL-6 or IL-6Rα can modulate IL-6 signaling. For instance, the anti-IL-6Rα antibody tocilizumab is used in the treatment of diseases like rheumatoid arthritis. In modeling studies, differences in the pharmacokinetics and interactions of anti-IL-6 and anti-IL-6Rα antibodies have been observed, with studies showing that certain antibodies can effectively suppress IL-6 signaling and alter the dose-response curves of these interactions. +2. **Role in Pathways:** + - IL6 signaling occurs through two main pathways: + - The classical pathway involves a membrane-bound IL-6 receptor (IL-6Rα). + - The trans-signaling pathway involves a soluble IL-6 receptor (sIL-6Rα). + - These pathways lead to the formation of a complex that activates the phosphorylation of gp130-bound Janus kinase (Jak) family proteins, followed by the phosphorylation of STAT3 (signal transducer and activator of transcription 3). -Overall, IL-6 is an important molecule in the biological system being modeled, particularly in the context of immune regulation and inflammatory diseases. Its signaling pathways and interactions with other molecules are critical to understanding the disease mechanisms and developing therapeutic interventions." -mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130,sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context from the document, the species 'sgp130' is described as a molecule involved in the inhibition of IL-6 trans-signaling. This characterization stems from its fusion form, sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is utilized to explore therapeutic applications, such as for conditions like Crohn’s disease. Here are the key points regarding sgp130: +3. **Interactions with Other Molecules:** + - IL6 forms a dimer/complex with IL-6Rα or sIL-6Rα, which then associates with a gp130 coreceptor to form a hexameric receptor complex. + - This complex initiates downstream signaling critical for immune responses. + - There are interactions with therapeutic antibodies, such as those targeting IL-6 or IL-6Rα, which can modulate its activity, an approach used in diseases like rheumatoid arthritis. -1. **Biological Function**: sgp130 functions primarily as an inhibitor of IL-6 trans-signaling. This signaling pathway is significant because it mediates inflammation and is implicated in various inflammatory diseases. The role of sgp130 in natural physiology appears to involve the regulation or modulation of IL-6 signaling pathways by binding to the IL-6/sIL-6Rα complex. +4. **Importance in the Biological System:** + - In diseases like Crohn’s disease, IL6-mediated signaling is significant due to its role in promoting inflammatory responses and affecting chemokine secretion, leading to prolonged inflammation. + - Targeting IL6 pathways is a therapeutic strategy used to control excessive inflammation and treat autoimmune diseases. -2. **Role in Pathways**: sgp130 is involved in the IL-6 signaling pathway. It functions to compete with, and hence regulate, IL-6 and its receptor (sIL-6Rα). This regulation is important because excessive IL-6 signaling is associated with inflammatory conditions. +In conclusion, IL6 is a highly influential cytokine in immune regulation, particularly in inflammatory and autoimmune conditions, where it plays roles in cell survival, signaling pathways, and interactions with therapeutic agents." +mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130,"Based on the provided context, the species 'sgp130' appears to be a component involved in the signaling pathways mediated by interleukin-6 (IL-6), specifically in the context of IL-6 trans-signaling. Here is a summary of relevant information about sgp130 based on the provided documents: -3. **Interactions with Other Molecules**: sgp130 interacts specifically with the IL-6/sIL-6Rα complex, indicating a competition for binding that can attenuate downstream signaling effects typically mediated by this complex. This interaction is a critical component of its inhibitory action. +1. **Biological Function:** + - sgp130 is a soluble form of gp130, which is involved in signal transduction for IL-6 and other cytokines. + - It is involved in inhibiting IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex. This indicates that sgp130 can modulate inflammatory responses mediated by IL-6. -4. **Importance in the Biological System Being Modeled**: While sgp130 is present at high concentrations compared to free IL-6, the sensitivity analyses from the models suggest that small changes in sgp130 levels have minimal effects on the system dynamics due to its high baseline level. Its impact seems to be less pronounced under typical physiological conditions; however, it can be significant under therapeutic conditions when used in high doses as sgp130Fc. +2. **Role in Pathways:** + - sgp130 specifically inhibits IL-6 trans-signaling, which typically occurs when the IL-6/sIL-6Rα complex interacts with membrane-bound gp130 on target cells. By binding with the complex, sgp130 prevents this interaction, potentially reducing pathological signaling associated with diseases such as Crohn’s disease. -Overall, sgp130 plays a regulatory role in the IL-6 pathway, and its therapeutic potential lies in its ability to inhibit IL-6 trans-signaling, albeit requiring high and frequent dosing for effectiveness in models such as Crohn's disease." +3. **Interactions with Other Molecules:** + - sgp130 interacts with the complex formed by IL-6 and its soluble receptor, sIL-6Rα. This interaction is a key mechanism by which sgp130 exerts its inhibitory effects on IL-6 mediated signaling. + +4. **Importance in the Biological System:** + - The context indicates that sgp130 is present in high baseline concentrations compared to IL-6, suggesting its physiological role as a moderator of IL-6 activity. + - The high baseline level of sgp130 and its excess relative to IL-6 suggest that it can effectively suppress IL-6 trans-signaling under normal conditions. + - The model described suggests that despite its high concentration, sgp130 has a minimal effect on system dynamics unless present in very high doses. This may reflect the physiological buffering role it plays to protect against excessive IL-6 activity. + - However, sgp130-based therapies may not be as effective as treatments targeting IL-6 or sIL-6Rα directly, due to its relatively lower influence on the system dynamics in terms of biomarker changes. + +In summary, sgp130 is important as a regulatory molecule in cytokine signaling pathways, particularly those involving IL-6, with potential therapeutic implications in modulating inflammatory and immune responses." +mw810ff751_fa4e_4143_bd50_169b3e325e1e,sR_IL6_sgp130,"Based on the provided context, 'sR_IL6_sgp130' is likely a component that is involved in the IL-6 signaling pathway, which is known to play a crucial role in inflammatory responses and immune regulation. The context refers to sgp130, which is described as a fusion protein that combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein, named sgp130Fc, is used to inhibit IL-6 trans-signaling. + +### Biological Function: +sR_IL6_sgp130 is not directly mentioned in the text, but based on similar components, it likely functions to modulate the IL-6 signaling pathway. In particular, sR_IL6_sgp130 might interact with the IL-6/sIL-6R complex, playing a role in inhibiting the trans-signaling process. + +### Role in Pathways: +The IL-6 signaling pathway is addressed in the context of both Classical and Trans signaling. While classical signaling involves IL-6 binding to membrane-bound IL-6 receptor (IL-6R) and gp130, trans-signaling involves IL-6 binding to soluble IL-6R (sIL-6R), allowing it to interact with gp130 on cells that do not express IL-6R. sR_IL6_sgp130 would participate in the inhibition of trans-signaling by binding to the IL-6/sIL-6R complex. + +### Interactions with Other Molecules: +In the context of the modeling study, sgp130Fc is assumed to bind the IL-6/sIL-6R complex with similar affinity to natural sgp130. This suggests that sR_IL6_sgp130 might also interact with IL-6, sIL-6R, and potentially compete or interfere with their binding to gp130, effectively inhibiting signaling pathways downstream. + +### Importance in the Biological System: +The presence of sgp130 in excess compared to free IL-6 indicates its potential role as a regulatory buffer in the signaling pathway. The study suggests that the system's sensitivity to changes in sgp130 levels is low unless there are significant deviations from baseline levels. This implies that while sgp130 (and by extrapolation, sR_IL6_sgp130) is important, its effects on the system dynamics are subtle unless present in large amounts, reaffirming its regulatory role. + +In summary, sR_IL6_sgp130 is inferred to be a critical modulator in the IL-6 signaling pathway, particularly involved in regulating the trans-signaling pathway by interacting with the IL-6/sIL-6R complex and potentially influencing inflammatory and immune responses." +mw114aa90f_5f5b_4fe8_9406_361c8489b6a1,CRP,"Based on the provided context, CRP, or C-reactive protein, is a biomarker commonly used to assess inflammation in the body. Here is a summary of relevant background information regarding CRP: + +1. **Biological Function**: CRP is a protein found in the blood, produced by the liver, and its levels increase in response to inflammation. It is part of the body's acute phase response to inflammation, infection, or injury. + +2. **Role in Pathways**: CRP is a key inflammatory marker often assessed in clinical settings to evaluate inflammation levels. It is used to monitor diseases like Crohn's disease, where inflammation is a characteristic feature. The context suggests its levels are affected by treatments targeting IL-6 signaling, which is a pathway involved in immune responses and inflammation. + +3. **Interactions with Other Molecules**: The context highlights interactions between CRP and interleukin-6 (IL-6) signaling pathways. IL-6 is a cytokine that activates the acute phase response, leading to increased CRP production. Treatments that target IL-6 or its receptor (IL-6Rα) can lead to a decrease in CRP levels by mitigating inflammation. + +4. **Importance in the Biological System Being Modeled**: CRP serves as a significant marker for inflammation in the model described. The model evaluates the effectiveness of different treatment strategies for managing inflammation, particularly in conditions like Crohn's disease, by measuring changes in CRP levels. The modulation of CRP through therapeutic interventions indicates the model's ability to simulate the inflammatory response to drug treatments. + +Overall, CRP is critical for monitoring and understanding inflammatory processes and the effectiveness of interventions in inflammatory diseases." +mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc,sR,"From the provided documents, there is no specific mention of a species named 'sR' with the ID mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc. However, there are references to molecules and components related to the IL-6 signaling pathway, such as sIL-6R (soluble IL-6 receptor) and sgp130, which are involved in IL-6 mediated signaling. + +### Inferred Background Information about 'sR': + +1. **Biological Function:** + - Based on similar naming conventions, 'sR' could potentially refer to a soluble receptor or a molecule that has a regulatory or auxiliary role in signaling pathways, possibly related to cytokine signaling like IL-6. + +2. **Role in Pathways:** + - If 'sR' is associated with processes similar to sIL-6R, it may be involved in modulating cytokine actions. Soluble receptors like sIL-6R often bind cytokines in the bloodstream, influencing their bioavailability and activity. + +3. **Interactions with Other Molecules:** + - Soluble receptors typically interact with ligands or other receptor components (e.g., cytokines such as IL-6). They may act as either inhibitors by sequestering the ligand or enhancers by stabilizing receptor complexes. + - Related interactions could involve complex formation with cytokine molecules and possibly other receptors such as gp130. + +4. **Importance in the Biological System Being Modeled:** + - In the context of the IL-6 signaling described, 'sR' may play a role in modulating inflammatory responses or other gene expression pathways through its interaction with signaling molecules. + - It might be significant in balancing the dynamics of cytokine signaling, similar to how sgp130 is described as having minimal immediate impacts unless present in vastly altered concentrations. + +Since there is no explicit information on 'sR', the above inferences are drawn from typical functions and roles of soluble receptors in cytokine signaling pathways as exemplified by the mentioned components like sIL-6R." +mw03db56ac_8dc6_4931_ae82_fef706d2ee3d,sR_IL6,"Based on the provided context and general knowledge about similar biological components, the species ""sR_IL6"" appears to refer to the soluble receptor component related to the cytokine Interleukin-6 (IL-6). Below is a summary of relevant background information: + +1. **Biological Function**: + - sR_IL6, likely reflecting ""soluble IL-6 receptor"" (sIL-6R), is a part of the IL-6 signaling pathway. This soluble receptor can bind to IL-6, allowing it to interact with gp130, a signal-transducing receptor component, and mediate downstream signaling. + +2. **Role in Pathways**: + - IL-6 can signal through classical and trans-signaling pathways. The classical pathway involves the membrane-bound IL-6 receptor, while the trans-signaling pathway involves the soluble IL-6 receptor (sIL-6R). In the latter, sR_IL6 binds to IL-6, forming a complex that can interact with membrane-bound gp130 to initiate intracellular signaling cascades. + +3. **Interactions with Other Molecules**: + - sR_IL6 forms a complex with IL-6, known as the IL-6/sIL-6R complex. This complex can be sequestered by another protein called sgp130, which negatively regulates IL-6 signaling by preventing it from interacting with cell surface gp130. + - The interaction between IL-6/sR_IL6 and gp130 leads to the activation of the Jak/STAT3 signaling pathway, which is pivotal for mediating immune and inflammatory responses. + +4. **Importance in the Biological System**: + - The soluble receptor sR_IL6 is important in expanding the range of cells that can respond to IL-6, as not all cells express the membrane-bound IL-6 receptor. Through trans-signaling, it facilitates cellular responses in a broader repertoire of cell types, including those implicated in inflammation and immune responses. + - In the context of the multiscale model outlined in the document, sR_IL6 and its interactions are crucial in understanding mechanisms underlying diseases such as Crohn's disease and in evaluating therapeutic interventions targeting IL-6 signaling pathways. + +In summary, sR_IL6 plays a significant role in mediating IL-6-related signaling pathways, influencing immune regulation and inflammation, and is a critical component in the computational modeling of related diseases." +mwf345ed7a_0622_403c_b816_c8749a2c9ded,Ab,"The context provided from the documents appears to be focused on a biological or pharmacological study, particularly related to the immune response involving interleukin pathways and potentially antibodies. However, there is no direct information or explicit mention of the species or molecule named 'Ab' with the ID provided. + +Based on the typical use of ""Ab"" in biological contexts, especially when mentioned alongside dose response and serum concentrations, it likely refers to an antibody. The context involves interactions within the IL-6 signaling pathway, common in studies involving inflammatory diseases such as Crohn’s disease (CD), and it details the effects of targeting interleukin-6 (IL-6), its receptor (IL-6Rα), and their complex. + +Given this information, 'Ab' could refer to: + +1. **Biological Function**: 'Ab' functions as an antibody, possibly designed to bind to specific antigens like IL-6 or IL-6Rα, potentially modulating immune responses by inhibiting these targets to reduce inflammation or related symptoms. + +2. **Role in Pathways**: It plays a role in the IL-6 signaling pathway, likely targeting either IL-6, IL-6Rα, or their complex, which is crucial in mediating inflammatory responses. + +3. **Interactions with Other Molecules**: 'Ab' would interact with IL-6, IL-6Rα, and possibly the IL-6/sIL-6Rα complex. This interaction aims to reduce the signaling through the IL-6 pathway, which is implicated in inflammatory processes. + +4. **Importance in the Biological System Being Modeled**: In the context of this study, 'Ab' is an important therapeutic agent intended to suppress inflammatory markers such as C-reactive protein (CRP), as suppression of CRP would indicate reduced inflammation, which is crucial in diseases like inflammatory bowel diseases. + +Overall, while explicit information on 'Ab' is not provided, it can be inferred that 'Ab' is an antibody used to intervene in inflammatory signaling pathways by targeting components of the IL-6 signaling system." +mw1da111f2_a036_4392_8512_015005bdcbb7,Ab_sR,"The context provided does not contain specific information about the species named 'Ab_sR' (ID: mw1da111f2_a036_4392_8512_015005bdcbb7). However, we can infer certain aspects based on the context and general biological knowledge related to similar components. + +In the context given, there are discussions around IL-6 (Interleukin-6), sIL-6R (soluble IL-6 receptor), and their interactions. These are critical components of the IL-6 signaling pathway, which is significant in the regulation of immune responses, inflammation, and hematopoiesis. Particularly, the IL-6/sIL-6R complex is involved in the trans-signaling pathway, affecting various biological processes, such as acute-phase protein production in the liver (e.g., CRP - C-reactive protein) and potentially impacting inflammation and immune response regulation. + +Given this context, if 'Ab_sR' is presumed to be a molecule or species related to these pathways, it might play a role in interacting with IL-6 or its receptor components, such as sIL-6R, thereby influencing the pathway's function. If 'Ab_sR' is akin to an antibody, as suggested by the prefix ""Ab,"" it might be involved in modulating the IL-6 signaling through binding to IL-6, sIL-6R, or the IL-6/sIL-6R complex, potentially affecting immune signaling and inflammation. + +If 'Ab_sR' has an inhibitory function similar to that of an antibody targeting IL-6 or sIL-6R, it could contribute to downregulating excessive inflammatory responses, thus playing a protective role in conditions characterized by inflammation, like autoimmune diseases or chronic inflammatory states. + +In summary, without explicit details, 'Ab_sR' might be theorized to interact within the IL-6 signaling pathway, potentially moderating its activity and influencing broader biological functions related to inflammation and immune response regulation." +mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac,Ab_sR_IL6,"From the context provided, there is no direct mention of a biological species or molecule named 'Ab_sR_IL6'. However, I can infer what it might be based on the context and general understanding of similar biological components. + +Given the provided context, which involves IL-6 (Interleukin-6) and sIL-6R (soluble Interleukin-6 receptor), it is likely that 'Ab_sR_IL6' refers to an antibody directed against a complex involving these molecules. Here’s a possible breakdown of what 'Ab_sR_IL6' might represent based on the context: + +1. **Biological Function:** + - If 'Ab_sR_IL6' stands for an antibody targeting the soluble IL-6 receptor (sIL-6R) or the IL-6/sIL-6R complex, its primary biological function would be to inhibit the interaction of IL-6 with its receptor. This can prevent downstream signaling pathways that are activated by IL-6 binding, which are known to play roles in inflammatory and immune responses. + +2. **Role in Pathways:** + - IL-6 is involved in the JAK/STAT signaling pathway, leading to the activation of STAT3 and transcription of specific genes, including ones involved in inflammation. The antibody would act to disrupt this signaling pathway by preventing IL-6 from binding to the sIL-6R and further associating with the membrane-bound IL-6 receptor (IL-6R) and gp130, a signal transducer molecule. + +3. **Interactions with Other Molecules:** + - The 'Ab_sR_IL6' likely interacts with sIL-6R or the IL-6/sIL-6R complex to form a binding complex that prohibits IL-6-related signaling cascades. + - This interaction would affect the circulation of IL-6 and sIL-6R, and consequently, the levels of C-reactive protein (CRP) in systems such as the liver, as indicated by the discussion around CRP suppression. + +4. **Importance in the Biological System Being Modeled:** + - In the context of immune regulation, particularly relating to conditions like Crohn’s disease or rheumatoid arthritis, inhibiting IL-6 signaling through the action of the antibody could provide therapeutic benefits by reducing inflammation. + - The model suggests that targeting both IL-6 and IL-6/sIL-6R (potentially by an antibody like 'Ab_sR_IL6') might yield enhanced therapeutic benefits compared to targeting IL-6 alone. + +This inference leverages general knowledge about the IL-6 pathway and common antibody strategies in therapeutic interventions." +CRP_Suppression___,CRP Suppression (%),"Based on the context provided, ""CRP Suppression (%)"" appears to be a measurement or output rather than a biological species or molecule. It is related to the suppression or reduction of serum C-reactive protein (CRP) levels, which can be tracked as a percentage decrease from baseline levels. Here is the inferred background information: + +1. **Biological Function**: CRP is a protein produced by the liver in response to inflammation. It is a common marker used in clinical settings to assess acute inflammation and is part of the immune response. + +2. **Role in Pathways**: CRP is part of the inflammatory response pathway. It is typically upregulated in response to pro-inflammatory cytokines such as Interleukin-6 (IL-6). The context suggests that anti-IL-6 or anti-IL-6 receptor (IL-6R) treatments are being used to modulate CRP levels by reducing inflammation. + +3. **Interactions with Other Molecules**: In the context of anti-IL-6 and anti-IL-6R treatments, CRP levels are affected by these interventions, which target the IL-6 signaling pathway. The suppression of CRP is used as an indicator of the effectiveness of these treatments, implying that IL-6 and its receptor play significant roles in the regulation of CRP levels. + +4. **Importance in the Biological System**: The reduction in serum CRP levels, reflected as ""CRP Suppression (%)"", is used as a biomarker to assess the efficacy of treatments targeting IL-6 signaling. This makes CRP suppression a crucial readout in models studying inflammation and therapeutic interventions aimed at reducing inflammation. + +Therefore, while ""CRP Suppression (%)"" is not a biological species or molecule, it serves as a quantitative measure of the effectiveness of interventions targeting inflammation, specifically through the IL-6 pathway. The context indicates its use in evaluating the impact of various anti-inflammatory strategies." +CRP____of_baseline,CRP (% of baseline),"Based on the provided context and general knowledge, here is the background information about ""CRP (% of baseline)"": + +1. **Biological Function**: + - CRP stands for C-reactive protein, which is a substance produced by the liver in response to inflammation. It is a well-known biomarker for inflammation and can indicate the presence of inflammatory diseases or other conditions. + +2. **Role in Pathways**: + - CRP is involved in the immune system's response to inflammation. It functions by binding to lysophosphatidylcholine on the surface of dead or dying cells and some types of bacteria. This binding activates the complement system via C1q, promoting phagocytosis by macrophages, which is a key component of the immune response to infection or injury. + +3. **Interactions with Other Molecules**: + - CRP interacts with other molecules within the immune system, such as complement proteins. In the context of the provided documents, CRP levels are used as an indicator of inflammation reduction in response to anti-IL-6Rα therapy. CRP levels decrease when the therapy is effective, signaling reduced inflammation. + +4. **Importance in the Biological System Being Modeled**: + - In the context of the provided documents, CRP (% of baseline) is a crucial measure used to evaluate the efficacy of a treatment involving anti–IL-6Rα (tocilizumab) antibodies. Tocilizumab is used to treat immune-mediated conditions by blocking the interleukin-6 receptor (IL-6Rα), thereby reducing inflammation. Monitoring CRP levels over time allows researchers to confirm the treatment's impact on systemic inflammation. + +The term ""CRP (% of baseline)"" refers to the proportion of CRP levels at any given time point compared to the initial baseline level before treatment commenced. This percentage allows researchers to assess changes in CRP concentration as a direct result of therapeutic interventions, providing insights into how effectively the treatment controls inflammation." +mw80848184_e2dd_47ce_86d7_7a21479342bd,gp130,"Gp130 is an important protein involved in the cytokine signaling pathway, particularly in relation to interleukin-6 (IL-6) signaling. It acts as a signal transducer for the IL-6 family of cytokines and plays a critical role in the assembly and function of cytokine receptor complexes. Specifically, gp130 serves as a common signal transducing subunit for the IL-6 receptor complex, which includes the IL-6 receptor alpha (IL-6Rα) and the IL-6 cytokine itself. + +### Biological Function: +- **Signal Transduction**: Gp130 participates in transmitting signals from the IL-6/IL-6Rα complex inside the cell, resulting in various biological responses. It forms a hexameric complex with IL-6 and its receptor, which is crucial for initiating downstream signaling pathways. +- **Regulator Role**: Soluble gp130 (sgp130) acts as a natural inhibitor of IL-6 trans-signaling. It binds to the IL-6/sIL-6Rα complex, preventing its interaction with membrane-bound gp130, thus modulating the activity of IL-6. + +### Role in Pathways: +- **IL-6 Pathway**: Gp130 is fundamental in the IL-6 signal transduction pathway. It is involved in the initiation of cascades like the JAK/STAT pathway, which is important for gene expression and immune response regulation. +- **Inflammatory Response**: Through its interaction with IL-6, gp130 is implicated in the inflammatory response and has been linked to diseases such as Crohn's disease. + +### Interactions with Other Molecules: +- **Complex Formation**: Gp130 interacts with IL-6 and soluble IL-6Rα to form a signaling complex. This interaction is necessary for the proper signal transduction and is the target for various therapeutic interventions. +- **Therapeutic Applications**: Fusion proteins like sgp130Fc are designed to inhibit IL-6 trans-signaling by binding the IL-6/sIL-6Rα complex, which is being explored for therapeutic use in inflammatory diseases like Crohn’s. + +### Importance in Biological Systems: +- **Regulatory Mechanism**: Gp130 serves as a key regulatory mechanism in cytokine signaling, influencing immune system activity and inflammation. +- **Disease Targeting**: Because of its central role in cytokine signaling, particularly in inflammatory pathways, gp130 and its soluble form are subjects of therapeutic interest, aiming to manage chronic inflammatory conditions. + +In summary, gp130 is a critical component in cytokine receptor signaling, primarily involved in IL-6-related pathways, playing a significant role in immune responses and being a potential point of interference for therapeutic strategies in inflammatory diseases." +mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a,R_IL6_gp130,"The species named 'R_IL6_gp130', provided with the ID mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a, seems to relate to components involved in the interleukin-6 (IL-6) signaling pathway, specifically centered around the gp130 protein. Although the context provided does not explicitly describe 'R_IL6_gp130', we can infer its characteristics based on similar biological components related to gp130 in IL-6 signaling. + +### Biological Function and Role in Pathways +- **gp130 (Glycoprotein 130)**: Serves as a signal-transducing receptor component shared by many cytokine receptors. It plays a central role in the IL-6 family cytokine signaling mechanisms. +- **IL-6 Signaling**: The molecule gp130 is integral to both classical and trans-signaling pathways of IL-6. The classical pathway involves the membrane-bound IL-6 receptor (IL-6R) and is primarily active in immune cells. Trans-signaling occurs via a soluble form of the IL-6 receptor (sIL-6R) and is more widely active, affecting cells that do not have the IL-6 receptor. + +### Interactions with Other Molecules +- **IL-6/JAK/STAT Pathway**: The gp130 acts as the signal transducer for IL-6-type cytokine receptors, leading to activation of the JAK/STAT signaling cascade, which is crucial for immune responses and inflammation. +- **Soluble gp130 (sgp130)**: This can act as a natural inhibitor for the IL-6/sIL-6R complex, limiting the effects of IL-6 trans-signaling. + +### Importance in Biological Systems +- **Inflammation and Immune Response**: The IL-6/gp130 pathway is significant in the regulation of inflammatory responses, relevant in various diseases such as Crohn's disease, as mentioned in the context. +- **Therapeutic Implications**: Variants or derivatives like sgp130Fc, which can inhibit IL-6 trans-signaling, are under study as therapeutic options for inflammatory diseases. + +In summary, while specific data about 'R_IL6_gp130' is not explicitly detailed in the context, by contextual association, it likely refers to a key player within the IL-6 signaling pathway, particularly involving gp130 in modulating immune and inflammatory processes through its interactions with IL-6 and its receptors." +mw4638f126_8cb8_4021_ab41_6ae195743ba0,sR_IL6,"The species referred to as 'sR_IL6' in the provided context is likely a soluble receptor related to the interleukin-6 (IL-6) signaling pathway. However, the context primarily references sIL-6R (soluble IL-6 receptor), which plays a prominent role in IL-6 signaling. + +Here is a summary of the background information and inferred roles of 'sR_IL6', based on the context and general knowledge of similar molecules: + +1. **Biological Function**: sIL-6R, which 'sR_IL6' appears to be closely related to, acts as a soluble form of the membrane-bound IL-6 receptor. It binds to IL-6 and can participate in inducing cellular responses, even in cells that do not express the membrane-bound receptor (classical signaling). + +2. **Role in Pathways**: sIL-6R is involved in IL-6 trans-signaling. In this process, the IL-6:sIL-6R complex can interact with the signaling receptor gp130 on cell surfaces, initiating signal transduction inside these cells. This pathway is crucial for modulating inflammatory responses and is distinct from classical IL-6 signaling that involves membrane-bound IL-6R. + +3. **Interactions with Other Molecules**: sIL-6R interacts with IL-6 to form the IL-6:sIL-6R complex. This complex can be sequestered by sgp130, another soluble receptor, which regulates its availability and, thus, the extent of trans-signaling. + +4. **Importance in the Biological System**: In the context of the immune system, especially in diseases like Crohn's Disease, the IL-6:sIL-6R complex is critical due to its potent regulatory effects on inflammation. Targeting this complex can alter the disease course by modulating immune responses, highlighting its importance in therapeutic strategies. + +Overall, sR_IL6 (assuming it is similar to sIL-6R) is a crucial component of the IL-6 signaling system, facilitating interactions that expand the range of cells responsive to IL-6, thereby playing a significant role in immune regulation and inflammation." +mw10315fa3_6f13_4618_bda8_a8694bd3c374,R,"Based on the provided context, the document discusses interleukin-6 receptor (IL-6R) and related biological components. Although the species 'R' with the ID 'mw10315fa3_6f13_4618_bda8_a8694bd3c374' is not explicitly mentioned, we can infer its context within the study. + +The document describes the role of soluble interleukin-6 receptor (sIL-6R) and the targeting of IL-6Rα by antibodies, suggesting that 'R' could be connected to IL-6R, possibly a subtype or variant involved in the pathway under study. The general biological functions and roles related to IL-6R could include: + +1. **Biological Function**: IL-6R is a part of the signaling pathway for interleukin-6 (IL-6), a cytokine involved in immune responses, inflammation, and hematopoiesis. + +2. **Role in Pathways**: IL-6R is essential for the classical IL-6 signaling pathway, which involves the dimerization of IL-6/IL-6R complex with gp130, activating JAK/STAT signaling that leads to gene transcription. + +3. **Interactions with Other Molecules**: IL-6R interacts with IL-6 to form a complex that associates with gp130. It can exist in a soluble form (sIL-6R), which allows IL-6 signaling in cells lacking the membrane-bound receptor, extending the cytokine's effects. + +4. **Importance in Biological Systems**: IL-6R is crucial in moderating immune responses and inflammation. It is a therapeutic target in inflammatory diseases, as seen in treatments involving anti-IL-6R antibodies (e.g., tocilizumab) to reduce inflammatory markers like C-reactive protein (CRP). + +Due to the lack of specific mention of 'R,' it might represent a molecule involved in the broader IL-6/IL-6R signaling pathway being studied, potentially playing a similar role in inflammation and immune regulation." +mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1,IL6,"IL-6 (Interleukin-6) is a cytokine, a type of signaling molecule involved in immune regulation. It plays a significant role in the body's inflammatory response and is implicated in various diseases, including Crohn’s disease and rheumatoid arthritis. In Crohn's disease, IL-6 contributes to enhanced T-cell survival and resistance to apoptosis in the lamina propria, along with elevated chemokine secretion. This suggests a critical role in promoting inflammation and immune dysregulation associated with the disease. + +IL-6 signaling can occur through two main pathways: + +1. **Classical Signaling Pathway**: This occurs via the membrane-bound IL-6 receptor (IL-6Rα). In this pathway, IL-6 binds to IL-6Rα, and the complex recruits a membrane-bound co-receptor, gp130, forming a heterotrimer that subsequently dimerizes to create an active hexameric IL-6 receptor complex. This complex initiates the phosphorylation of gp130-bound Janus kinase (Jak) family proteins and leads to the phosphorylation of signal transducer and activator of transcription 3 (STAT3). + +2. **Trans-Signaling Pathway**: This involves the soluble IL-6 receptor (sIL-6Rα) and allows IL-6 signaling to occur even in cells that do not express IL-6Rα. The IL-6/sIL-6Rα complex can bind to gp130 on various cell types, activating similar downstream signaling pathways as the classical pathway. Trans-signaling is thought to be particularly significant in disease contexts, like Crohn’s disease, where it can exacerbate inflammation. + +IL-6 interacts with other molecules such as anti-IL-6 and anti-IL-6Rα antibodies. These interactions are crucial in therapeutic contexts, such as using tocilizumab, an anti-IL-6Rα antibody, in treating rheumatoid arthritis. Tocilizumab has been observed to have nonlinear clearance, consistent with its interaction dynamics with IL-6Rα, validating certain modeling approaches. + +Overall, IL-6 is an essential player in immune responses and inflammation, making it a critical target in therapies designed to modulate immune responses in various inflammatory diseases." +mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83,R_IL6,"The context provided from the document does not directly mention a species or molecule explicitly named 'R_IL6' with the specific ID provided. However, we can infer potential information about 'R_IL6' by examining similar components within the context of IL-6 signaling and receptor interactions as mentioned in the document. + +### Biological Function: +- **R_IL6** is likely to be some variant or receptor related to interleukin-6 (IL-6). IL-6 is a cytokine involved in inflammatory and immune responses. Receptors related to IL-6, such as IL-6 receptors, mediate its signaling and subsequent biological effects. + +### Role in Pathways: +- **IL-6 signaling** involves complex pathways where IL-6 binds to its receptor (IL-6R), which can exist in both membrane-bound and soluble forms. This interaction often leads to the activation of the JAK/STAT signaling pathway, resulting in the phosphorylation of STAT3 (pSTAT3) and the transcription of genes involved in inflammation, such as SOCS and CRP (C-reactive protein). + +### Interactions with Other Molecules: +- **IL-6 interacts** with its receptor (IL-6R), either in a classical membrane-bound form or in a form that involves soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130), facilitating signal transduction. This signaling can be modulated by molecules like anti-IL-6 or anti-IL-6R antibodies, which are studied for their effects in treating conditions like rheumatoid arthritis. + +### Importance in Biological Systems: +- **The IL-6/IL-6R system** plays a significant role in immune regulation. It is involved in acute phase reactions, hematopoiesis, immune responses, and inflammation. It is particularly important in disease contexts such as Crohn's Disease and rheumatoid arthritis, where dysregulation of its signaling pathway can lead to pathological outcomes. + +Given these functions and interactions, it is reasonable to infer that 'R_IL6' is an essential component within the IL-6 signaling pathway, potentially representing a receptor or regulatory element of the pathway, playing a pivotal role in mediating immune responses and inflammation in the biological system being modeled." +mw0eb6c959_d408_45a0_a450_928b8c5876bb,Ractive,"The provided context does not specifically mention the species 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb). Therefore, based on the general content of the documents, which discuss immune regulation, particularly involving IL-6 in conditions like Crohn’s Disease and rheumatoid arthritis, I can infer some potential roles for a species hypothetically named 'Ractive' within this context. + +1. **Biological Function**: Given the context focuses on immune regulation mediated by the cytokine IL-6, 'Ractive' could be speculated to play a role as a regulatory molecule or modulator within immune signaling pathways, possibly interacting with cytokines or receptors involved in inflammatory responses. + +2. **Role in Pathways**: It might be involved in pathways related to cytokine signaling, particularly influencing the IL-6 pathway or its interaction with the soluble IL-6 receptor (sIL-6Rα), given the emphasis in the document on these components and their therapeutic targeting. + +3. **Interactions with Other Molecules**: 'Ractive' could potentially interact with IL-6, its receptor IL-6Rα, or the IL-6/sIL-6Rα complex, affecting their activity, stability, or clearance in the system, similar to how antibodies like tocilizumab are described to interact with these components in the context provided. + +4. **Importance in the Biological System**: If 'Ractive' were involved in modulating IL-6 activity, it could be crucial in maintaining or restoring immune balance, particularly in pathological conditions like Crohn’s disease where IL-6 plays a significant role in the disease mechanism. + +This speculative function aligns with the themes observed in the documents, which focus on the modulation of cytokine activity and therapeutic interventions in inflammatory diseases." +mw42054cd7_17af_46da_970c_7f99151906ad,STAT3,"STAT3, or Signal Transducer and Activator of Transcription 3, is a transcription factor that plays a crucial role in cellular signaling pathways. It is known for its involvement in mediating the effects of cytokines and growth factors, particularly the signaling of interleukin-6 (IL-6). Here's a summary of the relevant aspects of STAT3 based on the provided context and general knowledge: + +1. **Biological Function**: + - STAT3 is activated through phosphorylation, typically following the engagement of cytokine receptors such as those for IL-6. Once phosphorylated, pSTAT3 dimerizes and translocates into the nucleus, where it functions as a transcription factor to regulate gene expression. + +2. **Role in Pathways**: + - STAT3 is a core component of the JAK-STAT signaling pathway. In particular, it plays a significant role in the signaling events triggered by IL-6. This cytokine binds to its receptor, IL-6Rα, and utilizes the coreceptor gp130. The activation process results in the phosphorylation of STAT3, which then facilitates the transcription of target genes involved in various physiological processes. + +3. **Interactions with Other Molecules**: + - STAT3 interacts with other signaling molecules, including the Janus kinases (JAKs), which are responsible for its phosphorylation. Furthermore, the context mentions soluble forms of the IL-6 receptor (sIL-6Rα) and soluble gp130 (sgp130), which influence the activity of STAT3 by modulating the availability and activity of the IL-6 signaling complex. + - It also indirectly interacts with acute-phase proteins like C-reactive protein (CRP), with IL-6-induced STAT3 activity leading to increased CRP expression. + +4. **Importance in Biological Systems**: + - STAT3 plays a pivotal role in controlling inflammatory responses, promoting cellular growth and differentiation, particularly in response to IL-6 signaling, a critical regulator in immune responses and inflammation. + - In diseases such as Crohn’s disease, increased levels of pSTAT3 have been associated with disease activity, highlighting its importance in the pathology and as a potential therapeutic target. + +In summary, STAT3 is a central player in the IL-6 signaling pathway, influencing diverse biological processes and contributing to the pathology of various inflammatory diseases. Its regulation and interaction with other components make it a vital molecule in cellular signaling and a focal point in systems biology modeling." +mw39c2e431_fdc3_4964_be29_6ca856620b1b,pSTAT3,"Based on the context provided, pSTAT3 is the phosphorylated form of STAT3 (Signal Transducer and Activator of Transcription 3). Here is a summary of its relevant biological functions and roles based on the provided context and general knowledge: + +1. **Biological Function**: + pSTAT3 is a transcription factor that is activated through phosphorylation. This phosphorylation is primarily mediated by the Janus kinase (Jak) pathway, which is activated upon stimulation by cytokines such as interleukin 6 (IL-6). Once phosphorylated, pSTAT3 dimerizes and translocates to the cell nucleus, where it binds to specific DNA sequences to regulate the transcription of various genes. + +2. **Role in Pathways**: + - **IL-6 Signaling Pathway**: pSTAT3 acts as a critical intermediary in the IL-6 signaling cascade. The context suggests that IL-6 can facilitate pSTAT3 activation through both classical and trans-signaling mechanisms. Trans-signaling involves interactions with soluble IL-6 receptors (sIL-6R), while classical signaling involves membrane-bound IL-6 receptors. + - **JAK/STAT Pathway**: This is the primary signaling pathway for the activation of STAT3, where cytokines activate receptor-associated JAKs, which in turn phosphorylate STAT3, leading to the generation of pSTAT3. + +3. **Interactions with Other Molecules**: + - pSTAT3 interacts with the IL-6 receptor complex, which includes IL-6, sIL-6R, and gp130 (both membrane-bound and soluble forms like sgp130). The complex formation leads to the activation of downstream signaling, with pSTAT3 being a pivotal output molecule that drives gene transcription. + - SOCS (Suppressor of Cytokine Signaling) proteins are notable as negative regulators, limiting the activity of the JAK/STAT pathway and, consequently, pSTAT3 activity. + +4. **Importance in Biological Systems**: + The activation of pSTAT3 is associated with numerous cellular responses, including immune responses, inflammation, cell growth, and differentiation. Its presence and activity level in tissues like the gastrointestinal tract have been linked to inflammatory conditions, such as Crohn's Disease, as indicated by increased pSTAT3 in colon biopsies in such diseases. This highlights its importance in immune regulation and pathology. + +5. **Clinical Relevance**: + Due to its role in promoting inflammatory gene expression and cell proliferation, aberrant or prolonged activation of pSTAT3 is implicated in several diseases, including cancers and inflammatory bowel diseases. Therefore, it is a potential target for therapeutic interventions aimed at modulating immune responses or treating STAT3-driven pathologies. + +In summary, pSTAT3 is a crucial molecule in cytokine signaling pathways, modulating gene expression and contributing to inflammatory and proliferative processes in various tissues. Its regulation, particularly in pathological contexts like inflammatory bowel disease, makes it a significant focus for biological modeling and therapeutic targeting." +mwd5313618_89eb_4c8c_bc82_66f10f966349,CRP,"C-reactive protein (CRP) is a well-known marker in biological systems, particularly for inflammation. In the context of the provided documents, CRP serves as a biomarker to assess inflammation levels and the effectiveness of certain treatments, such as those targeting interleukin-6 (IL-6) signaling pathways in conditions like Crohn's disease. + +**Biological Function:** +CRP is an acute-phase protein produced by the liver. Its levels in the serum increase in response to inflammation caused by various factors, including infections and autoimmune diseases. CRP's primary biological function is to bind to the surface of dead or dying cells and some types of bacteria, thereby activating the complement system, which is a part of the immune response. + +**Role in Pathways:** +CRP is heavily involved in the immune response, mainly through its interaction with IL-6. IL-6 is a cytokine that plays a critical role in inflammation and immune response, and it induces the production of CRP. This connection makes CRP a useful indicator for evaluating the activity of the IL-6 pathway in various diseases. + +**Interactions with Other Molecules:** +- **IL-6 and IL-6Rα:** CRP production is stimulated by IL-6, which binds to IL-6 receptors and activates downstream signaling pathways that include the transcription of acute-phase proteins like CRP. +- **sgp130Fc:** The document mentions the use of sgp130Fc, an antagonist for IL-6 trans-signaling, suggesting interactions that potentially involve modulation of CRP levels when IL-6 signaling is inhibited. + +**Importance in the Biological System Being Modeled:** +CRP is central to the evaluation and modeling of inflammatory responses. In the simulation and modeling context in the document, CRP levels are utilized to validate models predicting the effect of IL-6 pathway inhibitors. Elevated CRP levels are commonly used as a surrogate marker for inflammation, making it a crucial component for assessing and predicting the effectiveness of treatments aimed at reducing inflammatory responses, especially in conditions like Crohn's disease. + +In summary, CRP's role as an indicator of inflammation, particularly through its interaction with the IL-6 pathway, makes it a critical focus in understanding and modeling inflammatory diseases and the effectiveness of treatments targeting these pathways." +mw2e464cf3_a09c_4b7c_9f3c_06720016a48e,sR,"The provided context primarily discusses the involvement of specific molecules and pathways related to the IL-6 signaling system, particularly focusing on the soluble interleukin-6 receptor (sIL-6R) and its interactions within the immune response system. However, it does not specifically mention a species or molecule identified solely as 'sR'. Given the context, it is possible to infer that 'sR' could refer to a soluble receptor component within this framework, possibly related to the IL-6 signaling pathway. + +### Inferred Background Information about 'sR': + +1. **Biological Function:** + - If 'sR' refers to a soluble receptor like sIL-6R, it functions by binding to a cytokine (such as IL-6) and subsequently participating in signaling pathways that alter cellular responses. Soluble receptors often regulate the activity of cytokines by either enhancing their range and stability or modifying their interaction with membrane-bound receptors. + +2. **Role in Pathways:** + - In the context of IL-6 signaling, soluble receptors like sIL-6R can form complexes with IL-6 (IL-6:sR complex), which can interact with other receptor subunits such as the signal-transducing element gp130. This initiates downstream signaling cascades like the JAK/STAT pathway, which affects the expression of various genes involved in inflammation and immune response. + +3. **Interactions with Other Molecules:** + - Potential interactions for 'sR' include binding with cytokines like IL-6 and interacting with other receptor components or proteins such as gp130. The formation of IL-6:sR:sgp130 complexes is one noted interaction, suggesting a role in modifying the cytokine's activity and downstream effects. + +4. **Importance in the Biological System:** + - The presence of soluble receptors modulates the intensity and duration of cytokine signaling. In the context described, the dynamics of 'sR' could be crucial in fine-tuning immune responses, particularly in inflammatory conditions. The precise balance and levels of such components can significantly influence physiological functions and pathological outcomes. + +Overall, while the context does not directly provide information about a species identified as 'sR', based on the descriptions of similar molecules, 'sR' may play a significant modulation role in cytokine signaling, impacting inflammation and immune system behavior." +mw36ea78c1_ed71_4def_96d3_857a442d7195,CRPExtracellular,"The context provided does not specifically mention a species or molecule named 'CRPExtracellular' with the exact ID given. However, based on the context and general biological knowledge, we can infer information about CRP, or C-reactive protein, which is mentioned multiple times. + +CRP, or C-reactive protein, is a protein found in blood plasma, whose levels rise in response to inflammation. It is considered an acute-phase protein produced by the liver in the presence of cytokines, particularly interleukin-6 (IL-6). The following points summarize the potential background information about 'CRPExtracellular' based on the context: + +1. **Biological Function**: CRP plays a critical role in the body's inflammatory response. It binds to the surface of dead or dying cells (and some types of bacteria) to activate the complement system, promoting phagocytosis by macrophages, which is part of the innate immune response. + +2. **Role in Pathways**: CRP is a significant marker in inflammation pathways. The context mentions its suppression as an indicator of the efficacy of treatments targeting IL-6 signaling. The model used in the study predicts serum CRP levels as a marker to assess the impact of drug treatments on inflammatory processes, like those seen in Crohn’s disease. + +3. **Interactions with Other Molecules**: CRP interacts with various components of the immune system, notably through its interaction with the complement system. However, the context primarily focuses on its relationship with IL-6 signaling. Antibodies targeting IL-6 or its receptor are shown to suppress CRP levels in the serum, reducing inflammation. + +4. **Importance in the Biological System Being Modeled**: In the context of the model described, CRP serves as a critical biomarker for inflammation and the efficacy of therapeutic interventions. The suppression of serum CRP levels is used as an output to evaluate the success of different treatment strategies for diseases characterized by overactive inflammation, like Crohn's disease. + +Given this information, 'CRPExtracellular' could refer to the presence of CRP in the extracellular fluid, where it exerts its effects and serves as an important marker for inflammation in the modeling system." +mw147d30ec_478e_4090_b496_128a131d29eb,sgp130,"Based on the provided context, sgp130 appears to be a biological molecule involved in the regulation of IL-6 signaling pathways. Here's a detailed summary of the relevant background information about sgp130: + +1. **Biological Function:** + - sgp130 is a fusion protein that combines the extracellular portion of the glycoprotein gp130 with the Fc region of human IgG1. This fusion protein, referred to as sgp130Fc, functions primarily as an inhibitor of IL-6 trans-signaling. IL-6 is a cytokine that plays a crucial role in immune response, inflammation, and hematopoiesis. + +2. **Role in Pathways:** + - sgp130 is part of the signaling pathways involving IL-6 and its receptor organization. It specifically targets the IL-6/sIL-6Rα complex, preventing the propagation of IL-6 trans-signaling in cells, which can have various downstream effects on immune and inflammatory responses. + +3. **Interactions with Other Molecules:** + - sgp130 interacts with the IL-6/sIL-6Rα complex, binding it with the same affinity as the natural gp130 receptor. This interaction is significant because it hinders the complex's activity in trans-signaling pathways, which are mediated by the presence of soluble IL-6 receptors and contribute to various biological processes, including inflammation. + +4. **Importance in the Biological System Being Modeled:** + - In the context of this specific model, sgp130 plays a role in modulating the IL-6-mediated signaling pathways. However, the sensitivity analysis in the model indicated that altering sgp130 levels has minimal effect on the steady-state values of output parameters due to the excess presence of sgp130 relative to IL-6. Consequently, sgp130-based therapies might be less effective if the goal is to significantly alter these pathways or conditions like Crohn’s disease, as the system shows relative insensitivity to sgp130 changes. + +In conclusion, sgp130 (as part of the sgp130Fc fusion protein) is primarily involved in the inhibition of IL-6 trans-signaling. Still, due to its high baseline level compared to IL-6, its impact on biological system dynamics may be limited without significant changes in sgp130 concentration." +mwab41493c_6349_45f1_a226_3030cfed0e06,sR_IL6_sgp130,"Based on the context provided and general knowledge of similar biological components, the species 'sR_IL6_sgp130' refers to complexes involving soluble IL-6 receptor components and the gp130 receptor protein. Here's a summary of the relevant information regarding these components: + +1. **Biological Function:** + - sR_IL6_sgp130 is likely involved in modulating the IL-6 signaling pathway. IL-6 is a cytokine that plays a critical role in immune responses, inflammation, and hematopoiesis. + +2. **Role in Pathways:** + - The document references IL-6 trans-signaling, it suggests that sR_IL6_sgp130 might be part of the mechanism to inhibit IL-6 signaling pathways. The soluble form of gp130 (sgp130) is noted as a negative regulator of IL-6 trans-signaling, which can act as a natural inhibitor by forming a complex with IL-6 and its soluble receptor sIL-6Rα, thus preventing further activation of membrane-bound gp130 receptor and subsequent signaling cascades. + +3. **Interactions with Other Molecules:** + - The context suggests that sgp130 interacts with the IL-6/sIL-6Rα complex. This interaction is essential because sgp130 cannot bind IL-6 directly unless IL-6 is associated with its soluble receptor, sIL-6Rα. + +4. **Importance in the Biological System Being Modeled:** + - In the context of inhibiting IL-6 trans-signaling, sgp130 (and likely sR_IL6_sgp130) plays a crucial role in maintaining balance by preventing excessive inflammatory responses. The simulations noted in the document suggest that therapeutically targeting sgp130 can have effects only at high doses, implicating its nuanced role in inflammation control through cytokine signaling pathways. + +5. **Modeling and Implications:** + - The system-level model mentioned discusses how sgp130 levels have little impact on steady-state parameters due to its high baseline concentration relative to free IL-6. This indicates sR_IL6_sgp130's role is more pronounced in scenarios where its concentration alters significantly, such as therapeutic applications for diseases like Crohn’s disease. + +In summary, sR_IL6_sgp130 is integral to the regulation of IL-6 signaling, primarily acting as an inhibitor in inflammatory processes, and its high natural abundance helps modulate these pathways under normal physiological conditions. +" +mwf405687b_7401_44ec_a0d6_4a2b35c13e8a,Ab_sR,"Based on the provided context, there is no direct mention or specific information about the species 'Ab_sR' with ID: mwf405687b_7401_44ec_a0d6_4a2b35c13e8a. However, we can infer potential characteristics and roles of 'Ab_sR' by examining the context, which discusses interleukin-6 (IL-6) signaling pathways and associated molecules like soluble IL-6 receptor (sIL-6R) and C-reactive protein (CRP). + +### Inferred Background Information about Ab_sR: + +1. **Biological Function:** + - If 'Ab_sR' is involved in the context of IL-6 signaling, it might be a receptor or a binding protein similar to sIL-6R. Soluble receptors often regulate cytokine activity by modulating their availability or by forming complexes that can engage in signaling. + +2. **Role in Pathways:** + - In the IL-6 signaling pathway, sIL-6R can form a complex with IL-6 that can interact with the signaling receptor gp130, initiating intracellular signaling cascades such as the JAK/STAT pathway. If 'Ab_sR' is analogous, it could play a role in modulating or facilitating such pathways. + +3. **Interactions with Other Molecules:** + - 'Ab_sR' may interact with cytokines like IL-6, potentially forming complexes that affect downstream signaling processes. Interaction with other receptors or signaling proteins such as gp130 is also a possibility if 'Ab_sR' serves a regulatory or modulating function similar to sIL-6R. + +4. **Importance in the Biological System:** + - In a biological system involving IL-6, components like sIL-6R are crucial for modulating inflammatory responses, highlighting their importance in immune regulation. Therefore, if 'Ab_sR' is part of this system, it may contribute significantly to balancing inflammatory signals and could be a target for therapeutic interventions aimed at controlling excessive inflammation. + +Given the context's focus on IL-6 and its receptors, 'Ab_sR' might represent a component analogously involved in modifying immune responses or influencing chronic inflammation states, similar to how the sIL-6R functions in IL-6 signaling pathways." +mw3667a5e1_02c9_44a0_acb4_b0431faa822d,Ab,"The species denoted as 'Ab' in the context appears to refer to an antibody. Specifically, this antibody seems to play a role in targeting and potentially neutralizing components involved in inflammatory pathways. + +### Biological Function: +- The context suggests that 'Ab' is an antibody directed against interleukin-6 (IL-6) or its receptor(s), particularly the soluble IL-6 receptor alpha (sIL-6Rα). Antibodies in this context are proteins designed to bind to specific antigens, such as IL-6 or its receptor, effectively inhibiting their activity. + +### Role in Pathways: +- The 'Ab' functions by engaging with and targeting the IL-6/sIL-6Rα complex, as part of a therapeutic mechanism aimed at reducing inflammation. This is evidenced by its usage in experiments modeling responses to treatment in conditions such as inflammatory bowel diseases (as indicated in other parts of the document). +- The targeting of this complex by the antibody is aimed at modulating immune responses, as IL-6 is a cytokine implicated in inflammatory and immune signaling pathways. + +### Interactions with Other Molecules: +- The antibody ('Ab') interacts specifically with IL-6 and sIL-6Rα. This interaction is significant because it prevents IL-6 from exerting its pro-inflammatory effects by blocking its interaction with cellular receptors or neutralizing it directly in circulation. +- The context also describes a dose-response relationship with serum C-reactive protein (CRP) suppression, which further underscores the antibody's role in inflammation modulation. CRP is an inflammatory marker, whose levels decrease with effective IL-6 pathway inhibition. + +### Importance in the Biological System Being Modeled: +- 'Ab' is essential in the system due to its therapeutic potential in inflammatory diseases. By inhibiting IL-6 and its receptor's interaction, the antibody can help reduce pathological inflammation. +- This is particularly relevant in clinical scenarios where overactive IL-6 signaling contributes to disease progression, such as in certain autoimmune or inflammatory conditions. + +Overall, 'Ab' is a critical component in the strategy for modulating inflammatory responses, highlighting its importance in both research and potential therapeutic applications." +mw772cbf20_3fc1_4800_ae59_77884f1ae333,Ab_R,"Based on the provided context from the documents, there is no specific mention or description of a biological species or molecule directly named 'Ab_R' with the ID provided. However, due to the context and typical content of systems biology research, we can infer some possibilities regarding what 'Ab_R' might represent, particularly in relation to antibodies or related biological components: + +1. **Biological Function**: Given the context involving antibodies and their interactions with IL-6 receptors, 'Ab_R' could likely denote an antibody or a component related to antibody functions. Antibodies (Ab) are crucial components of the immune system, responsible for identifying and neutralizing foreign objects such as bacteria and viruses. + +2. **Role in Pathways**: If 'Ab_R' is an antibody, it may play a role in immune signaling pathways, potentially as a therapeutic target or agent. Antibodies can either directly neutralize targets like IL-6 or IL-6Rα, or they can modulate signaling pathways by preventing these components from interacting and inducing inflammatory responses. + +3. **Interactions with Other Molecules**: The documents discuss anti–IL-6 and anti–IL-6Rα antibodies, as well as their interactions and dose responses. If 'Ab_R' is related to these antibodies, it might interact with interleukins or receptors involved in inflammatory responses, specifically IL-6 and its receptor IL-6Rα, affecting pathways such as cytokine signaling and inflammation regulation. + +4. **Importance in the Biological System Being Modeled**: In systems biology models, antibodies like 'Ab_R' can serve as model variables for predicting efficacy and outcomes of treatments targeting inflammatory pathways, such as those associated with chronic inflammatory diseases. The importance lies in their ability to modulate pivotal biochemical pathways, reduce inflammation markers such as CRP (C-reactive protein), and provide insights into therapeutic strategies. + +In conclusion, without explicit information regarding 'Ab_R', the inference is that it might be an antibody related to the systems being studied, possibly playing a role in modulating inflammation through interactions with components like IL-6 and IL-6Rα." +mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf,Ab_sR_IL6,"Based on the context provided, there is no explicit mention of a species or molecule named 'Ab_sR_IL6' with the ID mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf. However, the documents discuss the interactions of antibodies with the IL-6/sIL-6Rα complex and the effects of targeting this interaction on immune regulation, specifically mentioning IL-6 and IL-6 receptor components such as sIL-6R (soluble IL-6 receptor). + +Given this context, we can infer that 'Ab_sR_IL6' might represent an antibody related to the IL-6/sIL-6R interaction. Here is a generalized summary based on related knowledge about antibodies targeting the IL-6 pathway: + +### Background Information on Potential 'Ab_sR_IL6': + +- **Biological Function:** 'Ab_sR_IL6' is likely an antibody that targets the IL-6 signaling pathway, possibly binding to the soluble IL-6 receptor (sIL-6R) to modulate the interaction between IL-6 and its receptor. + +- **Role in Pathways:** This antibody would play a role in interrupting or modulating the IL-6 signaling pathway, which is involved in various immune and inflammatory responses. By targeting sIL-6R, the antibody may inhibit downstream signaling events, such as the activation of STAT3 and subsequent transcription of inflammatory gene products. + +- **Interactions with Other Molecules:** 'Ab_sR_IL6' may interact with sIL-6R, possibly preventing its interaction with IL-6 and the membrane-bound IL-6 receptor, thus affecting the formation of the IL-6/sIL-6R complex and its role in inflammatory signaling. + +- **Importance in the Biological System:** The antibody's potential inhibition of IL-6 signaling can be critical in controlling overactive immune responses associated with diseases like Crohn’s disease and rheumatoid arthritis. By moderating this pathway, 'Ab_sR_IL6' may contribute to the suppression of inflammatory markers such as C-reactive protein (CRP). + +This inference is made based on the context of targeting IL-6/sIL-6R pathways in therapeutic models and the general strategy of using monoclonal antibodies to modulate immune-related pathways." +mw7becb5fe_8da8_4285_a821_0d77ad811b62,sR_IL6,"Based on the context provided, specific information about the species named 'sR_IL6' (ID: mw7becb5fe_8da8_4285_a821_0d77ad811b62) is not directly mentioned. However, we can infer information based on the context regarding similar molecules like IL-6 and sIL-6R. + +### General Inference on sR_IL6: + +1. **Biological Function:** + - IL-6 is a cytokine involved in immune response regulation, often signaling through pathways that involve soluble receptors, such as sIL-6R (soluble interleukin-6 receptor). + - sIL-6R itself is instrumental in extending the range of IL-6 signaling to cells that do not naturally express the membrane-bound IL-6 receptor. + +2. **Role in Pathways:** + - IL-6 can signal through two main pathways: classical signaling, where it binds to membrane-bound IL-6R, and trans-signaling, involving sIL-6R. + - The IL-6/sIL-6R complex can be sequestered by sgp130, a soluble protein that modulates these pathways. + - These pathways are crucial in inflammation and immune regulation, often involved in diseases like Crohn's disease. + +3. **Interactions with Other Molecules:** + - IL-6 interacts with sIL-6R to form a complex that can engage with other components like gp130 (glycoprotein 130) to facilitate signaling. + - The context also suggests interactions with pharmacological agents, with antibody treatments targeting IL-6 or the IL-6/sIL-6R complex showing varying efficacy. + +4. **Importance in the Biological System:** + - In models focusing on immune regulation, especially in conditions like Crohn's disease, the IL-6/sIL-6R axis is critically evaluated for therapeutic targeting. + - Understanding its role is key for developing treatments that modulate immune responses pathological conditions. + +Overall, while 'sR_IL6' is not explicitly detailed in the documents, it can be inferred to have a function and role akin to soluble receptors facilitating cytokine signaling, with critical implications in inflammatory disease models." +mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca,gp130,"Gp130, also known as glycoprotein 130, is a crucial component of the interleukin-6 (IL-6) signaling pathway. It functions as a signal transducer in the receptor complex for IL-6, which plays a pivotal role in immune response, inflammation, and hematopoiesis. Gp130 itself does not bind IL-6 directly; instead, it forms part of the high-affinity receptor complex by associating with the IL-6/IL-6 receptor (IL-6R) complex. + +In the context of IL-6 signaling, gp130 is involved in classical signaling where it forms a hexameric structure with IL-6 and its membrane-bound IL-6R. Gp130 is also involved in trans-signaling, particularly through its interaction with soluble IL-6 receptor (sIL-6R). In this process, IL-6 can bind to sIL-6R, and the complex can then associate with gp130 on cells that do not express IL-6R, thereby expanding the range of cells responsive to IL-6 signaling. + +The document mentions a fusion protein, sgp130Fc, designed to inhibit IL-6 trans-signaling. This suggests that soluble gp130 (sgp130) acts as a natural inhibitor of the IL-6/sIL-6R complex, potentially preventing it from binding to membrane-bound gp130, thereby attenuating downstream signaling. This property of sgp130 is being explored as a therapeutic approach for conditions like Crohn's disease. + +In terms of its biological importance, gp130 is crucial for mediating normal and pathological responses through the IL-6 pathway. Its interactions with IL-6 and IL-6R complexes make it a significant player in inflammatory diseases and a potential target for therapeutic interventions aimed at modulating immune responses." +mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9,R_IL6_gp130,"Based on the context provided, it appears there is limited direct information about the species 'R_IL6_gp130' with the ID provided. However, we can synthesize and infer its role based on related information about similar biological components. + +### Inferred Background Information about R_IL6_gp130: + +- **Biological Function**: The naming 'R_IL6_gp130' suggests a complex involving Interleukin-6 (IL-6) and glycoprotein 130 (gp130). IL-6 is a cytokine involved in inflammatory and immune responses. gp130 is a signal transducing component of the IL-6 receptor complex. The complex's primary function is to mediate IL-6 signaling, which is crucial for the acute phase response and in regulating the immune and inflammatory responses. + +- **Role in Pathways**: The IL-6/gp130 complex is involved in the signaling pathways that result in the activation of intracellular cascades such as the JAK/STAT pathway. This signaling is essential for modulating gene expression in various tissues and contributes to physiological and pathophysiological processes. Specifically, the IL-6/gp130 signaling pathway plays a significant role in the inflammatory response observed in diseases like Crohn's disease, as noted in the context. + +- **Interactions with Other Molecules**: The context notes soluble forms of the receptor components, such as sgp130 and sIL-6R. These soluble factors can modulate IL-6 signaling by acting as competitive antagonists or facilitators of trans-signaling. The IL-6 can bind to its soluble receptor (sIL-6R), and the complex can then associate with both membrane-bound and soluble gp130 (sgp130) to continue the signal transduction process. + +- **Importance in the Biological System**: The IL-6/gp130 signaling complex is crucial in managing systemic inflammatory responses and its dysregulation can lead to chronic inflammatory conditions. It is an important therapeutic target, as seen in the research modeling the use of sgp130Fc to inhibit IL-6 trans-signaling for treating conditions like Crohn's disease. + +Overall, R_IL6_gp130 likely represents a functional interaction or complex in the IL-6 signaling pathway that plays a pivotal role in immune responses and inflammation. It is essential for understanding disease pathogenesis and designing therapeutic interventions targeting cytokine signaling." +mw6cce2109_0e32_4dd9_98ec_41173e8ef07d,Ractive,"The provided context does not contain direct information about the species named 'Ractive' with the specified ID. However, based on the context, which discusses a multiscale model of IL-6–mediated immune regulation in Crohn's Disease and involves components such as IL-6, IL-6Rα, and antibodies targeting these molecules, we can make some inferences. + +1. **Biological Function**: Ractive might be a signaling molecule or a biological entity involved in immune regulation, potentially analogous to IL-6 or its receptor. Its function could involve modulation of immune responses, particularly in inflammatory conditions such as Crohn's disease or rheumatoid arthritis. + +2. **Role in Pathways**: If Ractive functions similarly to IL-6 or its receptor, it may play a role in cytokine signaling pathways, which are crucial for immune system communication and regulation. These pathways often involve complex interactions and feedback mechanisms that control inflammation and immune response. + +3. **Interactions with Other Molecules**: Ractive could interact with receptors or form complexes that facilitate or inhibit signal transduction. This is akin to how IL-6 interacts with sIL-6Rα, forming a complex that can activate signaling pathways. + +4. **Importance in the Biological System**: In a model of immune regulation, Ractive could be important for understanding the dynamics of immune signaling, potentially serving as a target for therapeutic interventions in diseases characterized by dysregulated immune responses. + +Without specific information, these inferences rely on general knowledge of molecules involved in cytokine signaling and immune modulation, similar to IL-6 and its receptor pathways." +mw2b255f94_8018_4b99_bde8_918eeac45446,STAT3,"STAT3, or Signal Transducer and Activator of Transcription 3, is a transcription factor involved in various biological processes, particularly in signal transduction pathways. It is activated through phosphorylation, which is triggered by upstream cytokine signaling, such as the interleukin-6 (IL-6) signaling pathway. This phosphorylation site on STAT3 is known as pSTAT3, where 'p' denotes its phosphorylated state. + +**Biological Function:** +STAT3 serves as a key mediator in the cytokine signaling pathway that leads to the transcription of various genes. Upon activation, STAT3 translocates to the nucleus where it binds to specific DNA sequences to induce gene expression. The genes regulated by STAT3 are often involved in crucial biological processes such as immune response, cell growth, apoptosis, differentiation, and inflammation. + +**Role in Pathways:** +STAT3 is prominently involved in the IL-6 signaling cascade. Within this pathway, IL-6 binding leads to the formation of a receptor complex that includes IL-6Rα and gp130, which then activates associated Janus kinases (JAKs). The JAK kinases phosphorylate STAT3, enabling its dimerization and subsequent nuclear translocation. In the nucleus, STAT3 acts on specific response elements to modulate the expression of target genes. + +**Interactions with Other Molecules:** +STAT3 interacts with various components of the IL-6 signaling pathway, including the IL-6/sIL-6Rα complex and the gp130 receptor. Additionally, soluble gp130 (sgp130) can act as an inhibitor by sequestering the IL-6/sIL-6Rα complex, thereby modulating STAT3 activation. STAT3’s interactions are critical in modulating the inflammatory response as well as acute-phase reactions. + +**Importance in Biological Systems:** +In the context of disease, STAT3-mediated trans-signaling is significant, particularly because it is involved in the upregulation of acute-phase proteins like C-reactive protein (CRP) and in immune responses within tissues such as the gastrointestinal tract and liver. Aberrant STAT3 signaling has been implicated in various pathological conditions, including cancers and inflammatory disorders like Crohn’s disease. In these contexts, STAT3's regulatory role on gene expression can impact cellular proliferation and differentiation, making it a valuable target for therapeutic interventions." +mw48867e93_f170_44e8_ac7a_185b23e1bf3b,pSTAT3,"pSTAT3, or phosphorylated Signal Transducer and Activator of Transcription 3, is a key molecule in the realm of cellular biology, particularly in the context of its involvement in various signaling pathways. Based on the provided context, here is a summary of pSTAT3's roles and interactions: + +1. **Biological Function:** + pSTAT3 is a phosphorylated form of the STAT3 protein, which functions as a transcription factor. Once activated, it translocates to the cell nucleus where it influences the transcription of various genes. This process is crucial for mediating cellular responses to cytokines and growth factors. + +2. **Role in Pathways:** + The context mentions pSTAT3 in connection with the IL-6 signaling pathway. IL-6 binds to its receptor IL-6R, and through the co-receptor gp130, initiates signaling cascades that lead to the activation (phosphorylation) of STAT3. This activation is implicated in ""trans-signaling"" which is a form of signaling where the ligand-receptor complex activates cells that do not express the IL-6 receptor. + +3. **Interactions with Other Molecules:** + pSTAT3 is involved in a sophisticated network of interactions: + - It is downstream of the IL-6 signaling pathway, activated upon IL-6 binding to its receptor complex. + - The phosphorylated STAT3 can induce expression of various genes including those encoding the suppressor of cytokine signaling (SOCS) proteins, which are negative regulators of cytokine signaling. + - The context implies interactions with soluble forms of IL-6 receptor components, like sIL-6R and sgp130, which affect the signaling outcomes. + +4. **Importance in the Biological System:** + pSTAT3 is highlighted as an important signaling molecule in inflammatory responses, as noted in the mention of Crohn’s disease, an inflammatory bowel condition. In this context, elevated levels of pSTAT3 in colon biopsies suggest its role in mediating inflammatory processes. This underlines its importance not only in normal physiological responses but also in pathological conditions, making it a potential target for therapeutic intervention. + +Overall, pSTAT3 plays a vital role in cytokine signaling pathways, particularly those involving IL-6, and is crucial for cellular functions that relate to inflammation, differentiation, and immune responses." +mw0083d743_836f_4238_a17f_4602193d5bc0,geneProduct,"The context provided does not specifically mention the species or molecule identified by the name 'geneProduct' with the ID mw0083d743_836f_4238_a17f_4602193d5bc0. However, based on the context surrounding interactions with IL-6, sIL-6R, and sgp130, we can infer some potential roles and characteristics that a typical gene product may exhibit within this biological system, particularly related to IL-6 signaling. + +1. **Biological Function**: + - The reference to various gene products in conjunction with IL-6 pathways suggests that geneProduct might be involved in signaling pathways or could encode proteins that participate in immune responses. IL-6 is known to be a cytokine that plays a significant role in inflammation and the immune response. + +2. **Role in Pathways**: + - Gene products in the context of IL-6 are likely to be involved in mediating inflammatory responses or immune regulation. They could be participating in pathways involving Jak-STAT signaling, which is mentioned alongside IL-6 signaling processes in the text. + +3. **Interactions with Other Molecules**: + - The gene product could potentially interact with components of the IL-6 signaling pathway, such as the IL-6 receptor (IL-6R), soluble IL-6R (sIL-6R), and the signal transducer gp130. These interactions could influence downstream signaling cascades leading to diverse cellular responses. + +4. **Importance in the Biological System Being Modeled**: + - Considering the text emphasizes IL-6 signaling and its regulatory mechanisms, the gene product likely holds importance in modulating immune responses or inflammation. It might contribute to the fine-tuning of the system's response to inflammatory stimuli or be a target for therapeutic interventions to manage conditions related to excessive inflammation. + +Although specific details about the geneProduct are not mentioned in the provided context, understanding general roles of other gene products in similar pathways suggests potential functions and interactions that could be applicable." +mwd31f52cc_04e7_40e0_885f_c7b2d9e62215,sR,"Based on the provided context, the species named 'sR' appears to be associated with IL-6 signaling pathways. While the document doesn't explicitly detail the specific properties or function of 'sR', we can infer its potential role from related components mentioned, such as sIL-6R and sgp130. + +1. **Biological Function and Role in Pathways**: + - **sR** likely stands for a soluble receptor, analogous to sIL-6R (soluble Interleukin-6 Receptor), a well-known component in the IL-6 signaling pathway. + - Soluble receptors like sIL-6R can enhance the spectrum of the cytokine's action, allowing IL-6 to affect cells that do not express membrane-bound receptors. + - In the IL-6 signaling pathway, these molecules participate in the ""trans-signaling"" mechanism, where soluble receptors (e.g., sIL-6R) bind to IL-6, and this complex can then interact with membrane-bound gp130 on cells, initiating downstream signaling events. + +2. **Interactions with Other Molecules**: + - The context mentions interactions between IL-6, sIL-6R, and sgp130. It's likely that 'sR' interacts with one or more of these molecules, possibly forming a complex with IL-6 that subsequently engages with cell surface components like gp130. + - sgp130 acts as a natural inhibitor in the IL-6 signaling pathway by competitively inhibiting the binding of the IL-6/sIL-6R complex to cell surface gp130, thus regulating IL-6 trans-signaling activities. + +3. **Importance in the Biological System**: + - While the specific importance of 'sR' is not detailed, by analogy to sIL-6R, it could be critical in mediating and regulating responses to IL-6 in varied tissues, influencing gene expression changes and physiological responses. + - Alterations in its concentration, similar to sgp130, may have implications for the dynamics of the signaling pathway, with potential roles in inflammatory responses, metabolism, or immune regulation. + +In summary, although 'sR' is not specifically described, it is likely a component similar to sIL-6R, involved in facilitating IL-6 signaling through the trans-signaling pathway, with important interactions and regulatory roles in biological systems involving inflammatory responses." +mw2c9b0499_3325_4394_8af3_bbf653a944a0,IL6,"Based on the provided context, here is the background information about the molecule IL-6: + +### Biological Function +IL-6 (Interleukin 6) is a cytokine that plays a crucial role in immune regulation. It is involved in various immune responses, inflammation, and hematopoiesis (formation of blood cellular components). + +### Role in Pathways +IL-6 can signal through two main pathways: +1. **Classical Signaling Pathway:** Involves the membrane-bound IL-6 receptor (IL-6Rα). IL-6 binds to IL-6Rα, forming a dimer, which then associates with the gp130 receptor to form a hexameric complex. This complex triggers the phosphorylation of Janus kinase (Jak) family proteins and subsequently activates the STAT3 (Signal Transducer and Activator of Transcription 3) pathway. +2. **Trans-signaling Pathway:** Involves the soluble IL-6 receptor (sIL-6Rα). IL-6 binds to sIL-6Rα, and this complex interacts with gp130 on cell surfaces, similarly initiating the Jak/STAT3 signaling cascade. + +### Interactions with Other Molecules +IL-6 interacts with both its membrane-bound and soluble receptors (IL-6Rα and sIL-6Rα) to mediate its biological effects. The subsequent activation of gp130 and Jak/STAT3 signaling pathways is a key interaction. IL-6 also interacts with antibodies that target either IL-6 itself or its receptor, influencing signal suppression, which has therapeutic implications. + +### Importance in the Biological System Being Modeled +In the context of Crohn’s Disease, IL-6 is a significant contributor to the disease pathology. It enhances T-cell survival and apoptosis resistance in the intestinal lamina propria, leading to increased secretion of chemokines. This exacerbates the inflammatory response, making IL-6 a critical target for therapeutic interventions in Crohn's Disease. The suppression of IL-6 signaling through antibodies such as tocilizumab is of interest in controlling disease progression. + +This information contextualizes the role of IL-6 in immune modulation, particularly its contribution to inflammatory diseases such as Crohn's Disease, and underscores its importance as a therapeutic target." +mwd65b5b39_dc1b_4e77_a999_67277a880e5e,sgp130,"sgp130, as described in the context, refers to a biological molecule associated with the inhibition of IL-6 trans-signaling. It is a fusion protein that combines the extracellular portion of gp130 with the Fc region of human IgG1, known as sgp130Fc. This fusion protein has been experimentally shown to inhibit the IL-6/sIL-6Rα complex in cultured cells. sgp130 acts by binding to this complex, thus playing a role in modulating inflammatory pathways that are mediated by IL-6 trans-signaling. + +The molecule is particularly relevant in the context of therapeutic approaches for inflammatory diseases such as Crohn's disease. The document mentions simulations of intravenous dosing of sgp130Fc, which highlight its therapeutic potential, although its effectiveness is noted to be significant only at high and frequent doses. This suggests a potential therapeutic limitation due to the high baseline level of sgp130 in comparison to free IL-6, indicating that small changes in sgp130 levels have a minimal effect on system dynamics. + +In terms of its role in biological pathways, sgp130's primary function in this context is the regulation of the IL-6 trans-signaling pathway. It interacts specifically with the IL-6/sIL-6Rα complex, preventing the signaling cascade that would normally be activated by the interaction of IL-6 with its receptors. This interaction is crucial for reducing inflammation, especially in cases like Crohn's disease. + +In summary, sgp130 is important in systems biology as an inhibitor of the IL-6 trans-signaling pathway, possessing potential therapeutic uses in inflammatory diseases. However, its effectiveness is contingent upon achieving high concentrations due to its already high baseline levels compared to IL-6, thus making its role in modulating the pathway somewhat limited under normal physiological conditions." +mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3,sR_IL6_sgp130,"The species 'sR_IL6_sgp130' likely refers to a soluble form of the glycoprotein gp130 that interacts with the interleukin-6 (IL-6) signaling complex. From the context provided, it can be inferred that sR_IL6_sgp130 is involved in the inhibition of IL-6 trans-signaling pathways. Here is a breakdown of the potential role and importance of sR_IL6_sgp130 based on the provided text and general biological knowledge: + +1. **Biological Function**: sR_IL6_sgp130 likely functions as an inhibitor of the IL-6 trans-signaling pathway. Trans-signaling involves the interaction of IL-6 with its soluble receptor sIL-6Rα, which can then associate with membrane-bound or soluble gp130 to activate signaling. The role of sR_IL6_sgp130 would be to interrupt this process, thus modulating the cellular response to IL-6. + +2. **Role in Pathways**: In the context of IL-6 signaling, gp130 is a signal-transducing receptor component. Inhibition of the IL-6/sIL-6Rα complex formation by sR_IL6_sgp130 would prevent downstream signaling events such as the activation of the JAK/STAT pathway and its associated transcriptional activities (e.g., induction of CRP production in the liver). + +3. **Interactions with Other Molecules**: sR_IL6_sgp130 interacts directly with the IL-6/sIL-6Rα complex. By binding to this complex, it prevents the engagement and activation of membrane-bound gp130, thereby inhibiting downstream signaling. + +4. **Importance in the Biological System**: The document suggests that while sR_IL6_sgp130 (or sgp130Fc, a pharmacological derivative) can inhibit IL-6-driven signaling pathways, its effectiveness is contingent on very high concentrations due to the high baseline levels of sgp130 compared to IL-6. This implies that sR_IL6_sgp130 serves as a regulatory element within the immune signaling framework, potentially acting as a buffer or modulator to prevent excessive or aberrant IL-6 signaling, which is relevant in pathologies like inflammation or autoimmune diseases. + +In summary, sR_IL6_sgp130 plays a role as a modulator in IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, thus preventing further signal transduction through gp130-mediated pathways. While it has potential therapeutic implications, particularly in inflammatory conditions, its impact in the modeled biological system requires larger perturbations to observe significant effects due to its existing baseline levels." +mwf7796221_1fea_4274_a93e_c00adbf5778c,Ab,"Based on the provided context, there is no direct mention of the species 'Ab' with the ID 'mwf7796221_1fea_4274_a93e_c00adbf5778c'. However, the context provides information on antibody interactions, specifically related to IL-6 and IL-6 receptor α (IL-6Rα), suggesting that 'Ab' might refer to an antibody involved in such interactions. Here’s an inferred background based on the context: + +1. **Biological Function**: The abbreviation 'Ab' often refers to an antibody. Antibodies are crucial components of the immune system, responsible for identifying and neutralizing pathogens like bacteria and viruses. In this context, 'Ab' could be an antibody targeting IL-6 or its receptor IL-6Rα. + +2. **Role in Pathways**: IL-6 is a cytokine involved in various inflammatory and immune responses. The IL-6/IL-6Rα pathway is significant in inflammatory diseases. An antibody against IL-6 or IL-6Rα would play a role in modulating this pathway, potentially reducing inflammation by inhibiting the activity of IL-6. + +3. **Interactions with Other Molecules**: The 'Ab' in the context likely interacts with IL-6 and its receptor IL-6Rα. This interaction is aimed at blocking the cytokine signaling pathway, thereby reducing inflammation and associated symptoms. The context suggests that targeting both IL-6 and the IL-6/IL-6Rα complex can lead to enhanced therapeutic efficacy. + +4. **Importance in the Biological System**: In the biological model described, the antibody 'Ab' plays a critical therapeutic role. By targeting IL-6 and IL-6Rα, it helps manage conditions characterized by excessive inflammation, such as inflammatory bowel diseases, which aligns with the reference to changes in serum CRP (C-reactive protein) levels—a marker of inflammation response. + +In summary, although specific details about the species 'Ab' are not provided, it is likely an antibody functioning within an inflammatory pathway, targeting IL-6 and its receptor to mitigate inflammatory responses in diseases such as inflammatory bowel disease." +mw5d764bb8_5693_4ac8_9557_f65992cc5eb0,Ab_sR,"The provided context does not include specific information about the species named 'Ab_sR' (ID: mw5d764bb8_5693_4ac8_9557_f65992cc5eb0). However, I can infer some possibilities based on general knowledge about similar biological components within the described context. + +1. **Biological Function**: There is a mention of molecules like sIL-6R and IL-6Rα within the text. Typically, 'Ab' in 'Ab_sR' could refer to an antibody or related molecule. In biological systems, antibodies play a crucial role in the immune response by identifying and neutralizing foreign objects like bacteria and viruses. + +2. **Role in Pathways**: If 'Ab_sR' is an antibody, it may be involved in regulatory or signaling pathways. The context discusses the IL-6 signaling pathway, which is important for immune response mediation. Antibodies can modulate such pathways by targeting cytokines or their receptors to either promote or inhibit responses. + +3. **Interactions with Other Molecules**: The IL-6/sIL-6R complex is a subject of interest in the provided context, often interacting with other proteins like sgp130. Antibodies typically interact with antigens (specific target molecules), possibly modulating interactions between cytokines and their receptors or further downstream signaling molecules such as STAT3. + +4. **Importance in the Biological System Being Modeled**: In the given context, antibodies targeting components of the IL-6 pathway are evaluated for their potential in therapy (like CRP suppression), indicating the importance of these molecules in modulating inflammatory responses. Antibodies can be crucial in therapeutically managing conditions involving dysregulated cytokine signaling. + +Without specific information about 'Ab_sR', it is not possible to ascertain its precise function or interactions. However, based on the context involving IL-6 signaling and the mention of antibodies (likely abbreviation 'Ab'), 'Ab_sR' might be involved in similar biological processes." +mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2,Ab_sR_IL6,"The species ""Ab_sR_IL6"" appears to be involved in interactions with the soluble form of the interleukin-6 receptor (sIL-6Rα). Based on the context provided, and given the naming convention (Ab typically denotes an antibody), ""Ab_sR_IL6"" likely represents an antibody that targets the sIL-6Rα molecule. Although there is no explicit mention of ""Ab_sR_IL6"" in the documents, we can infer its role based on known biological interactions and the surrounding text. + +### Inferred Background Information about Ab_sR_IL6: + +1. **Biological Function**: + - ""Ab_sR_IL6"" is likely an antibody designed to interact with the soluble form of the interleukin-6 receptor, sIL-6Rα. Antibodies targeting cytokine receptors are typically used to modulate signal transduction pathways and manage inflammatory responses. + +2. **Role in Pathways**: + - The potential pathway involvement of ""Ab_sR_IL6"" is connected to the IL-6 signaling pathway. By targeting sIL-6Rα, this antibody may influence the downstream signaling of IL-6, a cytokine involved in immune regulation and inflammatory processes. + +3. **Interactions with Other Molecules**: + - It is likely that ""Ab_sR_IL6"" interacts specifically with sIL-6Rα, preventing its interaction with IL-6. This action could block or reduce the IL-6/sIL-6Rα complex formation, thereby affecting the downstream activation of signal transducer and activator of transcription 3 (STAT3) and other related genes and proteins. + +4. **Importance in the Biological System Being Modeled**: + - The targeting of the IL-6/sIL-6Rα complex is significant in the context of diseases characterized by exaggerated IL-6 signaling, such as Crohn's disease and rheumatoid arthritis. Antibodies like ""Ab_sR_IL6"" play a crucial role in diminishing the inflammatory response, potentially leading to decreased C-reactive protein (CRP) levels and amelioration of disease symptoms. + +In summary, while ""Ab_sR_IL6"" is not explicitly detailed in the provided documents, its inferred role as an antibody against sIL-6Rα suggests its importance as a therapeutic agent in managing IL-6 mediated pathways and inflammatory conditions." +mwbc2f5464_81e5_43fd_8b39_f5a2756af72f,Ab,"The provided documents include information that suggests 'Ab' refers to an antibody involved in targeting the interleukin-6 receptor (IL-6Rα) and its soluble form (sIL-6Rα). Here's a summary based on the context: + +### Biological Function +- **Ab** appears to be an antibody that specifically targets the IL-6 receptor (both membrane-bound and soluble forms, IL-6Rα/sIL-6Rα). +- It plays a role in modulating the immune response by interfering with the IL-6 signaling pathway. + +### Role in Pathways +- IL-6 is a cytokine involved in inflammatory and immune responses. The IL-6 receptor, which 'Ab' targets, is part of this pathway. +- Targeting both IL-6 and IL-6Rα/sIL-6Rα can enhance the suppression of CRP (C-reactive protein), a marker of inflammation, indicating that 'Ab' is involved in controlling inflammatory responses. + +### Interactions with Other Molecules +- The context suggests that 'Ab' interacts with IL-6, IL-6Rα, and sIL-6Rα. By binding these molecules, the antibody can alter their function, essentially blocking the downstream signaling of the IL-6 pathway. + +### Importance in the Biological System +- The use of this antibody ('Ab') represents a therapeutic strategy to dampen inflammatory responses, which could be important in treating inflammatory conditions or diseases such as inflammatory bowel diseases, as suggested by the context. +- The document discusses the antibody's dose-response effect on CRP suppression, highlighting its therapeutic potential in modifying disease progression or symptoms. + +In summary, 'Ab' is an antibody participating in anti-inflammatory processes by targeting and inhibiting key components of the IL-6 signaling pathway. This interaction plays a significant role in reducing inflammation and is relevant in pharmacological interventions for diseases characterized by elevated IL-6 activity." diff --git a/docs/notebooks/talk2knowledgegraphs/subgraph_generation_sheng+inigo.ipynb b/notebook/subgraph_generation.ipynb similarity index 59% rename from docs/notebooks/talk2knowledgegraphs/subgraph_generation_sheng+inigo.ipynb rename to notebook/subgraph_generation.ipynb index 95ef4710..f2763936 100644 --- a/docs/notebooks/talk2knowledgegraphs/subgraph_generation_sheng+inigo.ipynb +++ b/notebook/subgraph_generation.ipynb @@ -46,18 +46,9 @@ }, { "cell_type": "code", - "execution_count": 1, + "execution_count": 3, "metadata": {}, - "outputs": [ - { - "name": "stderr", - "output_type": "stream", - "text": [ - "/home/oneai/miniconda3/envs/py311/lib/python3.11/site-packages/tqdm/auto.py:21: TqdmWarning: IProgress not found. Please update jupyter and ipywidgets. See https://ipywidgets.readthedocs.io/en/stable/user_install.html\n", - " from .autonotebook import tqdm as notebook_tqdm\n" - ] - } - ], + "outputs": [], "source": [ "# Import necessary libraries\n", "import os\n", @@ -68,7 +59,7 @@ "from tqdm import tqdm\n", "from torch_geometric.utils import from_networkx\n", "import sys\n", - "sys.path.append('../../..')\n", + "sys.path.append('../')\n", "from aiagents4pharma.talk2knowledgegraphs.datasets.primekg import PrimeKG\n", "from aiagents4pharma.talk2knowledgegraphs.datasets.starkqa_primekg import StarkQAPrimeKG\n", "from aiagents4pharma.talk2knowledgegraphs.utils.embeddings.ollama import EmbeddingWithOllama\n", @@ -97,7 +88,7 @@ }, { "cell_type": "code", - "execution_count": 2, + "execution_count": 4, "metadata": {}, "outputs": [ { @@ -105,35 +96,15 @@ "output_type": "stream", "text": [ "Loading nodes of PrimeKG dataset ...\n", - "Downloading node file from https://dataverse.harvard.edu/api/access/datafile/6180617\n" - ] - }, - { - "name": "stderr", - "output_type": "stream", - "text": [ - "100%|██████████| 8.89M/8.89M [00:00<00:00, 22.4MiB/s]\n" - ] - }, - { - "name": "stdout", - "output_type": "stream", - "text": [ + "../../data/primekg/primekg_nodes.tsv.gz already exists. Loading the data from the local directory.\n", "Loading edges of PrimeKG dataset ...\n", - "Downloading edge file from https://dataverse.harvard.edu/api/access/datafile/6180616\n" - ] - }, - { - "name": "stderr", - "output_type": "stream", - "text": [ - "100%|██████████| 387M/387M [00:39<00:00, 9.76MiB/s] \n" + "../../data/primekg/primekg_edges.tsv.gz already exists. Loading the data from the local directory.\n" ] } ], "source": [ "# Define primekg data by providing a local directory where the data is stored\n", - "primekg_data = PrimeKG(local_dir=\"../../../../data/primekg/\")\n", + "primekg_data = PrimeKG(local_dir=\"../../data/primekg/\")\n", "\n", "# Invoke a method to load the data\n", "primekg_data.load_data()\n", @@ -171,9 +142,17 @@ }, { "cell_type": "code", - "execution_count": 3, + "execution_count": 31, "metadata": {}, "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/tmp/ipykernel_1377/1976418716.py:14: UserWarning: This pattern is interpreted as a regular expression, and has match groups. To actually get the groups, use str.extract.\n", + " ibd_nodes_df = ibd_nodes_df[ibd_nodes_df.node_type == \"disease\"].query(query_str, engine='python')\n" + ] + }, { "data": { "text/html": [ @@ -204,27 +183,11 @@ " \n", " \n", " \n", - " 27269\n", - " 27269\n", - " IL21-related infantile inflammatory bowel disease\n", - " MONDO\n", - " 14338\n", - " disease\n", - " \n", - " \n", - " 28158\n", - " 28158\n", - " inflammatory bowel disease\n", - " MONDO_grouped\n", - " 9960_12845_33643_11471_12831_12875_12941_13153...\n", - " disease\n", - " \n", - " \n", - " 29293\n", - " 29293\n", - " inflammatory bowel disease, immunodeficiency, ...\n", + " 35649\n", + " 35649\n", + " neoplasm of mature T-cells or NK-cells\n", " MONDO\n", - " 32601\n", + " 5169\n", " disease\n", " \n", " \n", @@ -252,30 +215,6 @@ " disease\n", " \n", " \n", - " 37785\n", - " 37785\n", - " ulcerative colitis (disease)\n", - " MONDO\n", - " 5101\n", - " disease\n", - " \n", - " \n", - " 39013\n", - " 39013\n", - " immune dysregulation-inflammatory bowel diseas...\n", - " MONDO\n", - " 16542\n", - " disease\n", - " \n", - " \n", - " 39787\n", - " 39787\n", - " immune dysregulation with inflammatory bowel d...\n", - " MONDO\n", - " 33967\n", - " disease\n", - " \n", - " \n", " 83770\n", " 83770\n", " Crohn's colitis\n", @@ -315,83 +254,35 @@ " 22901\n", " disease\n", " \n", - " \n", - " 99680\n", - " 99680\n", - " immune dysregulation-inflammatory bowel diseas...\n", - " MONDO\n", - " 33968\n", - " disease\n", - " \n", - " \n", - " 99681\n", - " 99681\n", - " inflammatory bowel disease-recurrent sinopulmo...\n", - " MONDO\n", - " 33969\n", - " disease\n", - " \n", " \n", "\n", "" ], "text/plain": [ - " node_index node_name \\\n", - "27269 27269 IL21-related infantile inflammatory bowel disease \n", - "28158 28158 inflammatory bowel disease \n", - "29293 29293 inflammatory bowel disease, immunodeficiency, ... \n", - "35814 35814 Crohn ileitis and jejunitis \n", - "35815 35815 small bowel Crohn disease \n", - "37784 37784 Crohn disease \n", - "37785 37785 ulcerative colitis (disease) \n", - "39013 39013 immune dysregulation-inflammatory bowel diseas... \n", - "39787 39787 immune dysregulation with inflammatory bowel d... \n", - "83770 83770 Crohn's colitis \n", - "95279 95279 Crohn jejunoileitis \n", - "95280 95280 gastroduodenal Crohn disease \n", - "97088 97088 perianal Crohn disease \n", - "99325 99325 Crohn disease of the esophagus \n", - "99680 99680 immune dysregulation-inflammatory bowel diseas... \n", - "99681 99681 inflammatory bowel disease-recurrent sinopulmo... \n", + " node_index node_name node_source \\\n", + "35649 35649 neoplasm of mature T-cells or NK-cells MONDO \n", + "35814 35814 Crohn ileitis and jejunitis MONDO_grouped \n", + "35815 35815 small bowel Crohn disease MONDO \n", + "37784 37784 Crohn disease MONDO_grouped \n", + "83770 83770 Crohn's colitis MONDO \n", + "95279 95279 Crohn jejunoileitis MONDO \n", + "95280 95280 gastroduodenal Crohn disease MONDO \n", + "97088 97088 perianal Crohn disease MONDO \n", + "99325 99325 Crohn disease of the esophagus MONDO \n", "\n", - " node_source node_id \\\n", - "27269 MONDO 14338 \n", - "28158 MONDO_grouped 9960_12845_33643_11471_12831_12875_12941_13153... \n", - "29293 MONDO 32601 \n", - "35814 MONDO_grouped 709_21207 \n", - "35815 MONDO 5539 \n", - "37784 MONDO_grouped 5011_5535 \n", - "37785 MONDO 5101 \n", - "39013 MONDO 16542 \n", - "39787 MONDO 33967 \n", - "83770 MONDO 5532 \n", - "95279 MONDO 708 \n", - "95280 MONDO 710 \n", - "97088 MONDO 5537 \n", - "99325 MONDO 22901 \n", - "99680 MONDO 33968 \n", - "99681 MONDO 33969 \n", - "\n", - " node_type \n", - "27269 disease \n", - "28158 disease \n", - "29293 disease \n", - "35814 disease \n", - "35815 disease \n", - "37784 disease \n", - "37785 disease \n", - "39013 disease \n", - "39787 disease \n", - "83770 disease \n", - "95279 disease \n", - "95280 disease \n", - "97088 disease \n", - "99325 disease \n", - "99680 disease \n", - "99681 disease " + " node_id node_type \n", + "35649 5169 disease \n", + "35814 709_21207 disease \n", + "35815 5539 disease \n", + "37784 5011_5535 disease \n", + "83770 5532 disease \n", + "95279 708 disease \n", + "95280 710 disease \n", + "97088 5537 disease \n", + "99325 22901 disease " ] }, - "execution_count": 3, + "execution_count": 31, "metadata": {}, "output_type": "execute_result" } @@ -399,13 +290,13 @@ "source": [ "# Query for nodes related to IBD\n", "\n", - "relevant_terms = ['inflammatory bowel disease', 'crohn', 'ulcerative colitis']\n", + "relevant_terms = [\"Crohn\", \"Interleukin-6\", \"T-cells\", \"(IL-6)\"]\n", "query_str = \"\"\n", "for idx in range(len(relevant_terms)): # Assuming relevant_terms is a list\n", " if idx == 0:\n", - " query_str += f'node_name_lower.str.contains(\"{relevant_terms[idx]}\")'\n", + " query_str += f'node_name_lower.str.contains(\"{relevant_terms[idx].lower()}\")'\n", " else:\n", - " query_str += f'or node_name_lower.str.contains(\"{relevant_terms[idx]}\")'\n", + " query_str += f'or node_name_lower.str.contains(\"{relevant_terms[idx].lower()}\")'\n", "\n", "# Get the nodes related to IBD\n", "ibd_nodes_df = primekg_nodes.copy()\n", @@ -431,7 +322,7 @@ }, { "cell_type": "code", - "execution_count": 4, + "execution_count": 6, "metadata": {}, "outputs": [ { @@ -471,76 +362,76 @@ " \n", " \n", " \n", - " 5988787\n", - " 37785\n", - " ulcerative colitis (disease)\n", - " MONDO\n", - " 5101\n", + " 6018395\n", + " 37784\n", + " Crohn disease\n", + " MONDO_grouped\n", + " 5011_5535\n", " disease\n", - " 7359\n", - " ADCY7\n", + " 2384\n", + " CRP\n", " NCBI\n", - " 113\n", + " 1401\n", " gene/protein\n", " associated with\n", " disease_protein\n", " \n", " \n", - " 5988788\n", - " 28158\n", - " inflammatory bowel disease\n", - " MONDO_grouped\n", - " 9960_12845_33643_11471_12831_12875_12941_13153...\n", + " 6018397\n", + " 83770\n", + " Crohn's colitis\n", + " MONDO\n", + " 5532\n", " disease\n", - " 7359\n", - " ADCY7\n", + " 2384\n", + " CRP\n", " NCBI\n", - " 113\n", + " 1401\n", " gene/protein\n", " associated with\n", " disease_protein\n", " \n", " \n", - " 5988789\n", - " 37785\n", - " ulcerative colitis (disease)\n", - " MONDO\n", - " 5101\n", + " 6018398\n", + " 37784\n", + " Crohn disease\n", + " MONDO_grouped\n", + " 5011_5535\n", " disease\n", - " 2874\n", - " PRDM1\n", + " 3088\n", + " DNMT3A\n", " NCBI\n", - " 639\n", + " 1788\n", " gene/protein\n", " associated with\n", " disease_protein\n", " \n", " \n", - " 5988790\n", - " 28158\n", - " inflammatory bowel disease\n", - " MONDO_grouped\n", - " 9960_12845_33643_11471_12831_12875_12941_13153...\n", + " 6018400\n", + " 83770\n", + " Crohn's colitis\n", + " MONDO\n", + " 5532\n", " disease\n", - " 2874\n", - " PRDM1\n", + " 3088\n", + " DNMT3A\n", " NCBI\n", - " 639\n", + " 1788\n", " gene/protein\n", " associated with\n", " disease_protein\n", " \n", " \n", - " 5988791\n", - " 37785\n", - " ulcerative colitis (disease)\n", - " MONDO\n", - " 5101\n", + " 6018401\n", + " 37784\n", + " Crohn disease\n", + " MONDO_grouped\n", + " 5011_5535\n", " disease\n", - " 2712\n", - " CASP3\n", + " 2057\n", + " FN1\n", " NCBI\n", - " 836\n", + " 2335\n", " gene/protein\n", " associated with\n", " disease_protein\n", @@ -561,11 +452,11 @@ " ...\n", " \n", " \n", - " 3304471\n", - " 34780\n", - " IRGM\n", + " 3304468\n", + " 34887\n", + " DENND1B\n", " NCBI\n", - " 345611\n", + " 163486\n", " gene/protein\n", " 35814\n", " Crohn ileitis and jejunitis\n", @@ -576,11 +467,11 @@ " disease_protein\n", " \n", " \n", - " 3310277\n", - " 5022\n", - " ITGAM\n", + " 3304469\n", + " 13365\n", + " CCNY\n", " NCBI\n", - " 3684\n", + " 219771\n", " gene/protein\n", " 35814\n", " Crohn ileitis and jejunitis\n", @@ -591,125 +482,99 @@ " disease_protein\n", " \n", " \n", - " 3313160\n", - " 2889\n", - " TGFB1\n", + " 3304470\n", + " 35156\n", + " FAM92B\n", " NCBI\n", - " 7040\n", + " 339145\n", " gene/protein\n", - " 29293\n", - " inflammatory bowel disease, immunodeficiency, ...\n", - " MONDO\n", - " 32601\n", + " 35814\n", + " Crohn ileitis and jejunitis\n", + " MONDO_grouped\n", + " 709_21207\n", " disease\n", " associated with\n", " disease_protein\n", " \n", " \n", - " 3314800\n", - " 9104\n", - " INAVA\n", + " 3304471\n", + " 34780\n", + " IRGM\n", " NCBI\n", - " 55765\n", + " 345611\n", " gene/protein\n", - " 28158\n", - " inflammatory bowel disease\n", + " 35814\n", + " Crohn ileitis and jejunitis\n", " MONDO_grouped\n", - " 9960_12845_33643_11471_12831_12875_12941_13153...\n", + " 709_21207\n", " disease\n", " associated with\n", " disease_protein\n", " \n", " \n", - " 3314949\n", - " 34967\n", - " IL21\n", + " 3310277\n", + " 5022\n", + " ITGAM\n", " NCBI\n", - " 59067\n", + " 3684\n", " gene/protein\n", - " 27269\n", - " IL21-related infantile inflammatory bowel disease\n", - " MONDO\n", - " 14338\n", + " 35814\n", + " Crohn ileitis and jejunitis\n", + " MONDO_grouped\n", + " 709_21207\n", " disease\n", " associated with\n", " disease_protein\n", " \n", " \n", "\n", - "

620 rows × 12 columns

\n", + "

290 rows × 12 columns

\n", "" ], "text/plain": [ - " head_index head_name head_source \\\n", - "5988787 37785 ulcerative colitis (disease) MONDO \n", - "5988788 28158 inflammatory bowel disease MONDO_grouped \n", - "5988789 37785 ulcerative colitis (disease) MONDO \n", - "5988790 28158 inflammatory bowel disease MONDO_grouped \n", - "5988791 37785 ulcerative colitis (disease) MONDO \n", - "... ... ... ... \n", - "3304471 34780 IRGM NCBI \n", - "3310277 5022 ITGAM NCBI \n", - "3313160 2889 TGFB1 NCBI \n", - "3314800 9104 INAVA NCBI \n", - "3314949 34967 IL21 NCBI \n", - "\n", - " head_id head_type \\\n", - "5988787 5101 disease \n", - "5988788 9960_12845_33643_11471_12831_12875_12941_13153... disease \n", - "5988789 5101 disease \n", - "5988790 9960_12845_33643_11471_12831_12875_12941_13153... disease \n", - "5988791 5101 disease \n", - "... ... ... \n", - "3304471 345611 gene/protein \n", - "3310277 3684 gene/protein \n", - "3313160 7040 gene/protein \n", - "3314800 55765 gene/protein \n", - "3314949 59067 gene/protein \n", - "\n", - " tail_index tail_name \\\n", - "5988787 7359 ADCY7 \n", - "5988788 7359 ADCY7 \n", - "5988789 2874 PRDM1 \n", - "5988790 2874 PRDM1 \n", - "5988791 2712 CASP3 \n", - "... ... ... \n", - "3304471 35814 Crohn ileitis and jejunitis \n", - "3310277 35814 Crohn ileitis and jejunitis \n", - "3313160 29293 inflammatory bowel disease, immunodeficiency, ... \n", - "3314800 28158 inflammatory bowel disease \n", - "3314949 27269 IL21-related infantile inflammatory bowel disease \n", + " head_index head_name head_source head_id head_type \\\n", + "6018395 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", + "6018397 83770 Crohn's colitis MONDO 5532 disease \n", + "6018398 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", + "6018400 83770 Crohn's colitis MONDO 5532 disease \n", + "6018401 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", + "... ... ... ... ... ... \n", + "3304468 34887 DENND1B NCBI 163486 gene/protein \n", + "3304469 13365 CCNY NCBI 219771 gene/protein \n", + "3304470 35156 FAM92B NCBI 339145 gene/protein \n", + "3304471 34780 IRGM NCBI 345611 gene/protein \n", + "3310277 5022 ITGAM NCBI 3684 gene/protein \n", "\n", - " tail_source tail_id \\\n", - "5988787 NCBI 113 \n", - "5988788 NCBI 113 \n", - "5988789 NCBI 639 \n", - "5988790 NCBI 639 \n", - "5988791 NCBI 836 \n", - "... ... ... \n", - "3304471 MONDO_grouped 709_21207 \n", - "3310277 MONDO_grouped 709_21207 \n", - "3313160 MONDO 32601 \n", - "3314800 MONDO_grouped 9960_12845_33643_11471_12831_12875_12941_13153... \n", - "3314949 MONDO 14338 \n", + " tail_index tail_name tail_source tail_id \\\n", + "6018395 2384 CRP NCBI 1401 \n", + "6018397 2384 CRP NCBI 1401 \n", + "6018398 3088 DNMT3A NCBI 1788 \n", + "6018400 3088 DNMT3A NCBI 1788 \n", + "6018401 2057 FN1 NCBI 2335 \n", + "... ... ... ... ... \n", + "3304468 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", + "3304469 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", + "3304470 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", + "3304471 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", + "3310277 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", "\n", " tail_type display_relation relation \n", - "5988787 gene/protein associated with disease_protein \n", - "5988788 gene/protein associated with disease_protein \n", - "5988789 gene/protein associated with disease_protein \n", - "5988790 gene/protein associated with disease_protein \n", - "5988791 gene/protein associated with disease_protein \n", + "6018395 gene/protein associated with disease_protein \n", + "6018397 gene/protein associated with disease_protein \n", + "6018398 gene/protein associated with disease_protein \n", + "6018400 gene/protein associated with disease_protein \n", + "6018401 gene/protein associated with disease_protein \n", "... ... ... ... \n", + "3304468 disease associated with disease_protein \n", + "3304469 disease associated with disease_protein \n", + "3304470 disease associated with disease_protein \n", "3304471 disease associated with disease_protein \n", "3310277 disease associated with disease_protein \n", - "3313160 disease associated with disease_protein \n", - "3314800 disease associated with disease_protein \n", - "3314949 disease associated with disease_protein \n", "\n", - "[620 rows x 12 columns]" + "[290 rows x 12 columns]" ] }, - "execution_count": 4, + "execution_count": 6, "metadata": {}, "output_type": "execute_result" } @@ -727,27 +592,21 @@ }, { "cell_type": "code", - "execution_count": 5, + "execution_count": 7, "metadata": {}, "outputs": [ { "data": { "text/plain": [ - "array([ 144, 179, 192, 279, 417, 625, 657, 729, 772,\n", - " 989, 1004, 1122, 1299, 1480, 1567, 1618, 1654, 1777,\n", - " 1990, 2012, 2057, 2078, 2111, 2139, 2329, 2384, 2543,\n", - " 2643, 2712, 2749, 2874, 2889, 2978, 2983, 3064, 3088,\n", - " 3233, 3259, 3333, 3414, 3460, 3469, 3474, 3484, 3495,\n", - " 3578, 3646, 4152, 4162, 4731, 4818, 4968, 4997, 5022,\n", - " 5195, 5385, 5720, 5805, 5915, 6168, 6175, 6229, 6428,\n", - " 6661, 7059, 7083, 7359, 7384, 7899, 7958, 8030, 8564,\n", - " 9104, 9454, 9763, 10113, 10191, 10919, 11103, 11134, 11199,\n", - " 11523, 11588, 12305, 12663, 12740, 12763, 12816, 13014, 13365,\n", - " 21972, 22105, 34623, 34776, 34777, 34778, 34779, 34780, 34781,\n", - " 34814, 34887, 34967, 35156])" + "array([ 144, 729, 989, 1122, 1480, 1567, 1618, 2057, 2111,\n", + " 2329, 2384, 2983, 3088, 3259, 3333, 3469, 3484, 3495,\n", + " 4162, 4997, 5022, 5195, 5385, 5720, 5915, 6168, 6175,\n", + " 6229, 6428, 6661, 7059, 7083, 7899, 7958, 10113, 10191,\n", + " 11134, 11523, 12305, 12663, 12763, 12816, 13014, 13365, 22105,\n", + " 34778, 34779, 34780, 34814, 34887, 35156])" ] }, - "execution_count": 5, + "execution_count": 7, "metadata": {}, "output_type": "execute_result" } @@ -775,7 +634,7 @@ }, { "cell_type": "code", - "execution_count": 6, + "execution_count": 8, "metadata": {}, "outputs": [], "source": [ @@ -805,7 +664,7 @@ }, { "cell_type": "code", - "execution_count": 7, + "execution_count": 9, "metadata": {}, "outputs": [], "source": [ @@ -835,7 +694,7 @@ }, { "cell_type": "code", - "execution_count": 8, + "execution_count": 10, "metadata": {}, "outputs": [ { @@ -875,76 +734,76 @@ " \n", " \n", " \n", - " 321759\n", - " 14118\n", - " Rose bengal\n", + " 322559\n", + " 14645\n", + " Methionine\n", " DrugBank\n", - " DB11182\n", + " DB00134\n", " drug\n", - " 3233\n", - " LTF\n", + " 6175\n", + " MTHFR\n", " NCBI\n", - " 4057\n", + " 4524\n", " gene/protein\n", - " carrier\n", + " enzyme\n", " drug_protein\n", " \n", " \n", - " 321763\n", - " 14038\n", - " Fluticasone furoate\n", + " 322560\n", + " 14833\n", + " Riboflavin\n", " DrugBank\n", - " DB08906\n", + " DB00140\n", " drug\n", - " 4152\n", - " ABCB1\n", + " 6175\n", + " MTHFR\n", " NCBI\n", - " 5243\n", + " 4524\n", " gene/protein\n", - " carrier\n", + " enzyme\n", " drug_protein\n", " \n", " \n", - " 321764\n", - " 14555\n", - " Technetium Tc-99m tetrofosmin\n", + " 322561\n", + " 14678\n", + " Folic acid\n", " DrugBank\n", - " DB09160\n", + " DB00158\n", " drug\n", - " 4152\n", - " ABCB1\n", + " 6175\n", + " MTHFR\n", " NCBI\n", - " 5243\n", + " 4524\n", " gene/protein\n", - " carrier\n", + " enzyme\n", " drug_protein\n", " \n", " \n", - " 321765\n", - " 14040\n", - " Fluticasone\n", + " 322562\n", + " 14834\n", + " Menadione\n", " DrugBank\n", - " DB13867\n", + " DB00170\n", " drug\n", - " 4152\n", - " ABCB1\n", + " 6175\n", + " MTHFR\n", " NCBI\n", - " 5243\n", + " 4524\n", " gene/protein\n", - " carrier\n", + " enzyme\n", " drug_protein\n", " \n", " \n", - " 322373\n", - " 14060\n", - " Levothyroxine\n", + " 322563\n", + " 14835\n", + " Benazepril\n", " DrugBank\n", - " DB00451\n", + " DB00542\n", " drug\n", - " 4152\n", - " ABCB1\n", + " 6175\n", + " MTHFR\n", " NCBI\n", - " 5243\n", + " 4524\n", " gene/protein\n", " enzyme\n", " drug_protein\n", @@ -965,129 +824,129 @@ " ...\n", " \n", " \n", - " 5731639\n", - " 4152\n", - " ABCB1\n", + " 5730796\n", + " 5385\n", + " SLC22A4\n", " NCBI\n", - " 5243\n", + " 6583\n", " gene/protein\n", - " 14498\n", - " Risdiplam\n", + " 14476\n", + " Testosterone cypionate\n", " DrugBank\n", - " DB15305\n", + " DB13943\n", " drug\n", " transporter\n", " drug_protein\n", " \n", " \n", - " 5731640\n", - " 4152\n", - " ABCB1\n", + " 5730797\n", + " 5385\n", + " SLC22A4\n", " NCBI\n", - " 5243\n", + " 6583\n", " gene/protein\n", - " 14908\n", - " Ubrogepant\n", + " 14477\n", + " Testosterone enanthate\n", " DrugBank\n", - " DB15328\n", + " DB13944\n", " drug\n", " transporter\n", " drug_protein\n", " \n", " \n", - " 5731641\n", - " 4152\n", - " ABCB1\n", + " 5730798\n", + " 5385\n", + " SLC22A4\n", " NCBI\n", - " 5243\n", + " 6583\n", " gene/protein\n", - " 14499\n", - " Elexacaftor\n", + " 14478\n", + " Testosterone undecanoate\n", " DrugBank\n", - " DB15444\n", + " DB13946\n", " drug\n", " transporter\n", " drug_protein\n", " \n", " \n", - " 5731642\n", - " 4152\n", - " ABCB1\n", + " 5730799\n", + " 5385\n", + " SLC22A4\n", " NCBI\n", - " 5243\n", + " 6583\n", " gene/protein\n", - " 14050\n", - " Prednisolone acetate\n", + " 14654\n", + " Choline salicylate\n", " DrugBank\n", - " DB15566\n", + " DB14006\n", " drug\n", " transporter\n", " drug_protein\n", " \n", " \n", - " 5731643\n", - " 4152\n", - " ABCB1\n", + " 5730800\n", + " 5385\n", + " SLC22A4\n", " NCBI\n", - " 5243\n", + " 6583\n", " gene/protein\n", - " 15752\n", - " Selpercatinib\n", + " 17318\n", + " Solriamfetol\n", " DrugBank\n", - " DB15685\n", + " DB14754\n", " drug\n", " transporter\n", " drug_protein\n", " \n", " \n", "\n", - "

2030 rows × 12 columns

\n", + "

734 rows × 12 columns

\n", "" ], "text/plain": [ - " head_index head_name head_source head_id \\\n", - "321759 14118 Rose bengal DrugBank DB11182 \n", - "321763 14038 Fluticasone furoate DrugBank DB08906 \n", - "321764 14555 Technetium Tc-99m tetrofosmin DrugBank DB09160 \n", - "321765 14040 Fluticasone DrugBank DB13867 \n", - "322373 14060 Levothyroxine DrugBank DB00451 \n", - "... ... ... ... ... \n", - "5731639 4152 ABCB1 NCBI 5243 \n", - "5731640 4152 ABCB1 NCBI 5243 \n", - "5731641 4152 ABCB1 NCBI 5243 \n", - "5731642 4152 ABCB1 NCBI 5243 \n", - "5731643 4152 ABCB1 NCBI 5243 \n", + " head_index head_name head_source head_id head_type \\\n", + "322559 14645 Methionine DrugBank DB00134 drug \n", + "322560 14833 Riboflavin DrugBank DB00140 drug \n", + "322561 14678 Folic acid DrugBank DB00158 drug \n", + "322562 14834 Menadione DrugBank DB00170 drug \n", + "322563 14835 Benazepril DrugBank DB00542 drug \n", + "... ... ... ... ... ... \n", + "5730796 5385 SLC22A4 NCBI 6583 gene/protein \n", + "5730797 5385 SLC22A4 NCBI 6583 gene/protein \n", + "5730798 5385 SLC22A4 NCBI 6583 gene/protein \n", + "5730799 5385 SLC22A4 NCBI 6583 gene/protein \n", + "5730800 5385 SLC22A4 NCBI 6583 gene/protein \n", "\n", - " head_type tail_index tail_name tail_source tail_id \\\n", - "321759 drug 3233 LTF NCBI 4057 \n", - "321763 drug 4152 ABCB1 NCBI 5243 \n", - "321764 drug 4152 ABCB1 NCBI 5243 \n", - "321765 drug 4152 ABCB1 NCBI 5243 \n", - "322373 drug 4152 ABCB1 NCBI 5243 \n", - "... ... ... ... ... ... \n", - "5731639 gene/protein 14498 Risdiplam DrugBank DB15305 \n", - "5731640 gene/protein 14908 Ubrogepant DrugBank DB15328 \n", - "5731641 gene/protein 14499 Elexacaftor DrugBank DB15444 \n", - "5731642 gene/protein 14050 Prednisolone acetate DrugBank DB15566 \n", - "5731643 gene/protein 15752 Selpercatinib DrugBank DB15685 \n", + " tail_index tail_name tail_source tail_id \\\n", + "322559 6175 MTHFR NCBI 4524 \n", + "322560 6175 MTHFR NCBI 4524 \n", + "322561 6175 MTHFR NCBI 4524 \n", + "322562 6175 MTHFR NCBI 4524 \n", + "322563 6175 MTHFR NCBI 4524 \n", + "... ... ... ... ... \n", + "5730796 14476 Testosterone cypionate DrugBank DB13943 \n", + "5730797 14477 Testosterone enanthate DrugBank DB13944 \n", + "5730798 14478 Testosterone undecanoate DrugBank DB13946 \n", + "5730799 14654 Choline salicylate DrugBank DB14006 \n", + "5730800 17318 Solriamfetol DrugBank DB14754 \n", "\n", " tail_type display_relation relation \n", - "321759 gene/protein carrier drug_protein \n", - "321763 gene/protein carrier drug_protein \n", - "321764 gene/protein carrier drug_protein \n", - "321765 gene/protein carrier drug_protein \n", - "322373 gene/protein enzyme drug_protein \n", + "322559 gene/protein enzyme drug_protein \n", + "322560 gene/protein enzyme drug_protein \n", + "322561 gene/protein enzyme drug_protein \n", + "322562 gene/protein enzyme drug_protein \n", + "322563 gene/protein enzyme drug_protein \n", "... ... ... ... \n", - "5731639 drug transporter drug_protein \n", - "5731640 drug transporter drug_protein \n", - "5731641 drug transporter drug_protein \n", - "5731642 drug transporter drug_protein \n", - "5731643 drug transporter drug_protein \n", + "5730796 drug transporter drug_protein \n", + "5730797 drug transporter drug_protein \n", + "5730798 drug transporter drug_protein \n", + "5730799 drug transporter drug_protein \n", + "5730800 drug transporter drug_protein \n", "\n", - "[2030 rows x 12 columns]" + "[734 rows x 12 columns]" ] }, - "execution_count": 8, + "execution_count": 10, "metadata": {}, "output_type": "execute_result" } @@ -1121,7 +980,7 @@ }, { "cell_type": "code", - "execution_count": 9, + "execution_count": 11, "metadata": {}, "outputs": [ { @@ -1161,76 +1020,76 @@ " \n", " \n", " \n", - " 6505784\n", - " 62703\n", - " Adherens junctions interactions\n", + " 6508862\n", + " 128783\n", + " Metalloprotease DUBs\n", " REACTOME\n", - " R-HSA-418990\n", + " R-HSA-5689901\n", " pathway\n", - " 8030\n", - " CDH3\n", + " 12305\n", + " NLRP3\n", " NCBI\n", - " 1001\n", + " 114548\n", " gene/protein\n", " interacts with\n", " pathway_protein\n", " \n", " \n", - " 6506102\n", - " 128079\n", - " Regulation of actin dynamics for phagocytic cu...\n", + " 6508863\n", + " 128804\n", + " The NLRP3 inflammasome\n", " REACTOME\n", - " R-HSA-2029482\n", + " R-HSA-844456\n", " pathway\n", - " 2139\n", - " ARPC2\n", + " 12305\n", + " NLRP3\n", " NCBI\n", - " 10109\n", + " 114548\n", " gene/protein\n", " interacts with\n", " pathway_protein\n", " \n", " \n", - " 6506103\n", - " 128183\n", - " EPHB-mediated forward signaling\n", + " 6508864\n", + " 129266\n", + " Purinergic signaling in leishmaniasis infection\n", " REACTOME\n", - " R-HSA-3928662\n", + " R-HSA-9660826\n", " pathway\n", - " 2139\n", - " ARPC2\n", + " 12305\n", + " NLRP3\n", " NCBI\n", - " 10109\n", + " 114548\n", " gene/protein\n", " interacts with\n", " pathway_protein\n", " \n", " \n", - " 6506104\n", - " 128022\n", - " RHO GTPases Activate WASPs and WAVEs\n", + " 6508865\n", + " 63064\n", + " Cytoprotection by HMOX1\n", " REACTOME\n", - " R-HSA-5663213\n", + " R-HSA-9707564\n", " pathway\n", - " 2139\n", - " ARPC2\n", + " 12305\n", + " NLRP3\n", " NCBI\n", - " 10109\n", + " 114548\n", " gene/protein\n", " interacts with\n", " pathway_protein\n", " \n", " \n", - " 6506105\n", - " 62931\n", - " Clathrin-mediated endocytosis\n", + " 6509093\n", + " 129136\n", + " RHOA GTPase cycle\n", " REACTOME\n", - " R-HSA-8856828\n", + " R-HSA-8980692\n", " pathway\n", - " 2139\n", - " ARPC2\n", + " 34814\n", + " TAGAP\n", " NCBI\n", - " 10109\n", + " 117289\n", " gene/protein\n", " interacts with\n", " pathway_protein\n", @@ -1251,142 +1110,142 @@ " ...\n", " \n", " \n", - " 3834665\n", - " 2543\n", - " CDH1\n", + " 3834560\n", + " 11134\n", + " NR1H4\n", " NCBI\n", - " 999\n", + " 9971\n", " gene/protein\n", - " 127731\n", - " Integrin cell surface interactions\n", + " 128001\n", + " Synthesis of bile acids and bile salts via 27-...\n", " REACTOME\n", - " R-HSA-216083\n", + " R-HSA-193807\n", " pathway\n", " interacts with\n", " pathway_protein\n", " \n", " \n", - " 3834666\n", - " 2543\n", - " CDH1\n", + " 3834561\n", + " 11134\n", + " NR1H4\n", " NCBI\n", - " 999\n", + " 9971\n", " gene/protein\n", - " 127617\n", - " Apoptotic cleavage of cell adhesion proteins\n", + " 128393\n", + " PPARA activates gene expression\n", " REACTOME\n", - " R-HSA-351906\n", + " R-HSA-1989781\n", " pathway\n", " interacts with\n", " pathway_protein\n", " \n", " \n", - " 3834667\n", - " 2543\n", - " CDH1\n", + " 3834562\n", + " 11134\n", + " NR1H4\n", " NCBI\n", - " 999\n", + " 9971\n", " gene/protein\n", - " 62703\n", - " Adherens junctions interactions\n", + " 62588\n", + " Endogenous sterols\n", " REACTOME\n", - " R-HSA-418990\n", + " R-HSA-211976\n", " pathway\n", " interacts with\n", " pathway_protein\n", " \n", " \n", - " 3834668\n", - " 2543\n", - " CDH1\n", + " 3834563\n", + " 11134\n", + " NR1H4\n", " NCBI\n", - " 999\n", + " 9971\n", " gene/protein\n", - " 128018\n", - " RHO GTPases activate IQGAPs\n", + " 128116\n", + " Nuclear Receptor transcription pathway\n", " REACTOME\n", - " R-HSA-5626467\n", + " R-HSA-383280\n", " pathway\n", " interacts with\n", " pathway_protein\n", " \n", " \n", - " 3834669\n", - " 2543\n", - " CDH1\n", + " 3834564\n", + " 11134\n", + " NR1H4\n", " NCBI\n", - " 999\n", + " 9971\n", " gene/protein\n", - " 129039\n", - " InlA-mediated entry of Listeria monocytogenes ...\n", + " 128204\n", + " SUMOylation of intracellular receptors\n", " REACTOME\n", - " R-HSA-8876493\n", + " R-HSA-4090294\n", " pathway\n", " interacts with\n", " pathway_protein\n", " \n", " \n", "\n", - "

1030 rows × 12 columns

\n", + "

610 rows × 12 columns

\n", "" ], "text/plain": [ - " head_index head_name \\\n", - "6505784 62703 Adherens junctions interactions \n", - "6506102 128079 Regulation of actin dynamics for phagocytic cu... \n", - "6506103 128183 EPHB-mediated forward signaling \n", - "6506104 128022 RHO GTPases Activate WASPs and WAVEs \n", - "6506105 62931 Clathrin-mediated endocytosis \n", - "... ... ... \n", - "3834665 2543 CDH1 \n", - "3834666 2543 CDH1 \n", - "3834667 2543 CDH1 \n", - "3834668 2543 CDH1 \n", - "3834669 2543 CDH1 \n", + " head_index head_name \\\n", + "6508862 128783 Metalloprotease DUBs \n", + "6508863 128804 The NLRP3 inflammasome \n", + "6508864 129266 Purinergic signaling in leishmaniasis infection \n", + "6508865 63064 Cytoprotection by HMOX1 \n", + "6509093 129136 RHOA GTPase cycle \n", + "... ... ... \n", + "3834560 11134 NR1H4 \n", + "3834561 11134 NR1H4 \n", + "3834562 11134 NR1H4 \n", + "3834563 11134 NR1H4 \n", + "3834564 11134 NR1H4 \n", "\n", " head_source head_id head_type tail_index \\\n", - "6505784 REACTOME R-HSA-418990 pathway 8030 \n", - "6506102 REACTOME R-HSA-2029482 pathway 2139 \n", - "6506103 REACTOME R-HSA-3928662 pathway 2139 \n", - "6506104 REACTOME R-HSA-5663213 pathway 2139 \n", - "6506105 REACTOME R-HSA-8856828 pathway 2139 \n", + "6508862 REACTOME R-HSA-5689901 pathway 12305 \n", + "6508863 REACTOME R-HSA-844456 pathway 12305 \n", + "6508864 REACTOME R-HSA-9660826 pathway 12305 \n", + "6508865 REACTOME R-HSA-9707564 pathway 12305 \n", + "6509093 REACTOME R-HSA-8980692 pathway 34814 \n", "... ... ... ... ... \n", - "3834665 NCBI 999 gene/protein 127731 \n", - "3834666 NCBI 999 gene/protein 127617 \n", - "3834667 NCBI 999 gene/protein 62703 \n", - "3834668 NCBI 999 gene/protein 128018 \n", - "3834669 NCBI 999 gene/protein 129039 \n", + "3834560 NCBI 9971 gene/protein 128001 \n", + "3834561 NCBI 9971 gene/protein 128393 \n", + "3834562 NCBI 9971 gene/protein 62588 \n", + "3834563 NCBI 9971 gene/protein 128116 \n", + "3834564 NCBI 9971 gene/protein 128204 \n", "\n", " tail_name tail_source \\\n", - "6505784 CDH3 NCBI \n", - "6506102 ARPC2 NCBI \n", - "6506103 ARPC2 NCBI \n", - "6506104 ARPC2 NCBI \n", - "6506105 ARPC2 NCBI \n", + "6508862 NLRP3 NCBI \n", + "6508863 NLRP3 NCBI \n", + "6508864 NLRP3 NCBI \n", + "6508865 NLRP3 NCBI \n", + "6509093 TAGAP NCBI \n", "... ... ... \n", - "3834665 Integrin cell surface interactions REACTOME \n", - "3834666 Apoptotic cleavage of cell adhesion proteins REACTOME \n", - "3834667 Adherens junctions interactions REACTOME \n", - "3834668 RHO GTPases activate IQGAPs REACTOME \n", - "3834669 InlA-mediated entry of Listeria monocytogenes ... REACTOME \n", + "3834560 Synthesis of bile acids and bile salts via 27-... REACTOME \n", + "3834561 PPARA activates gene expression REACTOME \n", + "3834562 Endogenous sterols REACTOME \n", + "3834563 Nuclear Receptor transcription pathway REACTOME \n", + "3834564 SUMOylation of intracellular receptors REACTOME \n", "\n", " tail_id tail_type display_relation relation \n", - "6505784 1001 gene/protein interacts with pathway_protein \n", - "6506102 10109 gene/protein interacts with pathway_protein \n", - "6506103 10109 gene/protein interacts with pathway_protein \n", - "6506104 10109 gene/protein interacts with pathway_protein \n", - "6506105 10109 gene/protein interacts with pathway_protein \n", + "6508862 114548 gene/protein interacts with pathway_protein \n", + "6508863 114548 gene/protein interacts with pathway_protein \n", + "6508864 114548 gene/protein interacts with pathway_protein \n", + "6508865 114548 gene/protein interacts with pathway_protein \n", + "6509093 117289 gene/protein interacts with pathway_protein \n", "... ... ... ... ... \n", - "3834665 R-HSA-216083 pathway interacts with pathway_protein \n", - "3834666 R-HSA-351906 pathway interacts with pathway_protein \n", - "3834667 R-HSA-418990 pathway interacts with pathway_protein \n", - "3834668 R-HSA-5626467 pathway interacts with pathway_protein \n", - "3834669 R-HSA-8876493 pathway interacts with pathway_protein \n", + "3834560 R-HSA-193807 pathway interacts with pathway_protein \n", + "3834561 R-HSA-1989781 pathway interacts with pathway_protein \n", + "3834562 R-HSA-211976 pathway interacts with pathway_protein \n", + "3834563 R-HSA-383280 pathway interacts with pathway_protein \n", + "3834564 R-HSA-4090294 pathway interacts with pathway_protein \n", "\n", - "[1030 rows x 12 columns]" + "[610 rows x 12 columns]" ] }, - "execution_count": 9, + "execution_count": 11, "metadata": {}, "output_type": "execute_result" } @@ -1406,54 +1265,42 @@ }, { "cell_type": "code", - "execution_count": 10, + "execution_count": 12, "metadata": {}, "outputs": [ { "data": { "text/plain": [ - "array([ 62341, 62347, 62348, 62373, 62376, 62394, 62400, 62401,\n", - " 62404, 62405, 62414, 62448, 62449, 62462, 62465, 62467,\n", - " 62469, 62472, 62476, 62477, 62483, 62543, 62571, 62573,\n", - " 62575, 62583, 62588, 62596, 62603, 62606, 62628, 62644,\n", - " 62651, 62655, 62657, 62672, 62675, 62691, 62692, 62697,\n", - " 62702, 62703, 62711, 62717, 62733, 62734, 62768, 62770,\n", - " 62805, 62807, 62836, 62865, 62916, 62925, 62931, 62968,\n", - " 62976, 62987, 62996, 63041, 63064, 63071, 63076, 127601,\n", - " 127615, 127616, 127617, 127619, 127620, 127624, 127628, 127629,\n", - " 127639, 127640, 127649, 127659, 127662, 127682, 127683, 127688,\n", - " 127691, 127693, 127694, 127695, 127696, 127726, 127727, 127728,\n", - " 127729, 127730, 127731, 127732, 127733, 127791, 127797, 127810,\n", - " 127814, 127815, 127833, 127835, 127856, 127858, 127866, 127867,\n", - " 127869, 127886, 127891, 127908, 127917, 127918, 127921, 127928,\n", - " 127958, 127960, 127971, 127977, 127999, 128001, 128002, 128003,\n", - " 128008, 128010, 128015, 128018, 128022, 128025, 128034, 128058,\n", - " 128065, 128071, 128072, 128073, 128074, 128078, 128079, 128080,\n", - " 128086, 128111, 128113, 128116, 128117, 128129, 128137, 128138,\n", - " 128139, 128158, 128165, 128170, 128176, 128183, 128186, 128191,\n", - " 128198, 128199, 128204, 128208, 128209, 128224, 128227, 128242,\n", - " 128243, 128244, 128253, 128254, 128270, 128271, 128272, 128273,\n", - " 128299, 128302, 128341, 128348, 128349, 128350, 128351, 128353,\n", - " 128360, 128378, 128381, 128393, 128395, 128396, 128399, 128430,\n", - " 128440, 128453, 128460, 128470, 128472, 128473, 128477, 128478,\n", + "array([ 62341, 62373, 62376, 62394, 62400, 62404, 62405, 62414,\n", + " 62448, 62462, 62465, 62467, 62469, 62472, 62483, 62543,\n", + " 62571, 62575, 62588, 62596, 62603, 62606, 62628, 62644,\n", + " 62651, 62691, 62692, 62697, 62702, 62711, 62717, 62733,\n", + " 62734, 62805, 62807, 62916, 62925, 62968, 62987, 62996,\n", + " 63041, 63064, 63071, 63076, 127601, 127639, 127640, 127682,\n", + " 127683, 127688, 127691, 127693, 127694, 127696, 127730, 127731,\n", + " 127733, 127791, 127797, 127815, 127835, 127856, 127858, 127866,\n", + " 127869, 127886, 127908, 127917, 127918, 127960, 127971, 127977,\n", + " 127999, 128001, 128010, 128015, 128025, 128034, 128058, 128065,\n", + " 128071, 128072, 128073, 128074, 128111, 128113, 128116, 128117,\n", + " 128137, 128138, 128139, 128158, 128165, 128176, 128191, 128198,\n", + " 128204, 128208, 128227, 128242, 128243, 128244, 128253, 128254,\n", + " 128272, 128299, 128302, 128341, 128348, 128350, 128353, 128360,\n", + " 128378, 128393, 128395, 128396, 128399, 128472, 128477, 128478,\n", " 128479, 128480, 128481, 128482, 128483, 128484, 128486, 128487,\n", - " 128497, 128498, 128499, 128500, 128501, 128503, 128527, 128535,\n", - " 128550, 128593, 128599, 128601, 128602, 128604, 128655, 128677,\n", - " 128715, 128759, 128766, 128767, 128779, 128781, 128782, 128783,\n", - " 128784, 128789, 128792, 128801, 128804, 128814, 128815, 128827,\n", - " 128828, 128829, 128830, 128832, 128835, 128837, 128838, 128841,\n", - " 128846, 128851, 128852, 128878, 128976, 128977, 128978, 128979,\n", - " 128980, 128981, 128988, 128990, 129007, 129015, 129016, 129021,\n", - " 129023, 129035, 129039, 129040, 129042, 129044, 129047, 129048,\n", - " 129052, 129099, 129110, 129124, 129125, 129126, 129127, 129128,\n", - " 129131, 129135, 129136, 129139, 129140, 129141, 129148, 129155,\n", - " 129167, 129181, 129183, 129190, 129195, 129196, 129197, 129198,\n", - " 129215, 129217, 129238, 129257, 129258, 129259, 129264, 129266,\n", - " 129289, 129294, 129296, 129302, 129303, 129310, 129355, 129360,\n", - " 129361, 129365, 129366, 129367])" + " 128497, 128498, 128499, 128500, 128501, 128503, 128550, 128593,\n", + " 128601, 128655, 128766, 128767, 128781, 128782, 128783, 128801,\n", + " 128804, 128814, 128815, 128827, 128828, 128829, 128830, 128832,\n", + " 128835, 128838, 128846, 128851, 128852, 128878, 128978, 128979,\n", + " 128980, 128981, 128990, 129007, 129015, 129016, 129035, 129040,\n", + " 129044, 129048, 129052, 129099, 129110, 129124, 129125, 129126,\n", + " 129127, 129128, 129131, 129136, 129139, 129140, 129141, 129148,\n", + " 129155, 129167, 129181, 129183, 129190, 129195, 129196, 129197,\n", + " 129198, 129215, 129217, 129238, 129257, 129258, 129259, 129266,\n", + " 129289, 129294, 129296, 129302, 129310, 129355, 129360, 129361,\n", + " 129366])" ] }, - "execution_count": 10, + "execution_count": 12, "metadata": {}, "output_type": "execute_result" } @@ -1481,7 +1328,7 @@ }, { "cell_type": "code", - "execution_count": 11, + "execution_count": 13, "metadata": {}, "outputs": [], "source": [ @@ -1511,7 +1358,7 @@ }, { "cell_type": "code", - "execution_count": 12, + "execution_count": 14, "metadata": {}, "outputs": [ { @@ -1551,76 +1398,76 @@ " \n", " \n", " \n", - " 6351294\n", + " 6351300\n", " 112487\n", " neutrophil degranulation\n", " GO\n", " 43312\n", " biological_process\n", - " 1990\n", - " FCGR2A\n", + " 3333\n", + " FPR2\n", " NCBI\n", - " 2212\n", + " 2358\n", " gene/protein\n", " interacts with\n", " bioprocess_protein\n", " \n", " \n", - " 6351300\n", + " 6351346\n", " 112487\n", " neutrophil degranulation\n", " GO\n", " 43312\n", " biological_process\n", - " 3333\n", - " FPR2\n", + " 5022\n", + " ITGAM\n", " NCBI\n", - " 2358\n", + " 3684\n", " gene/protein\n", " interacts with\n", " bioprocess_protein\n", " \n", " \n", - " 6351340\n", + " 6351457\n", " 112487\n", " neutrophil degranulation\n", " GO\n", " 43312\n", " biological_process\n", - " 2012\n", - " CXCR1\n", + " 12663\n", + " SLC11A1\n", " NCBI\n", - " 3577\n", + " 6556\n", " gene/protein\n", " interacts with\n", " bioprocess_protein\n", " \n", " \n", - " 6351341\n", - " 112487\n", - " neutrophil degranulation\n", + " 6351710\n", + " 103224\n", + " platelet degranulation\n", " GO\n", - " 43312\n", + " 2576\n", " biological_process\n", - " 3064\n", - " CXCR2\n", + " 2057\n", + " FN1\n", " NCBI\n", - " 3579\n", + " 2335\n", " gene/protein\n", " interacts with\n", " bioprocess_protein\n", " \n", " \n", - " 6351346\n", - " 112487\n", - " neutrophil degranulation\n", + " 6351714\n", + " 103224\n", + " platelet degranulation\n", " GO\n", - " 43312\n", + " 2576\n", " biological_process\n", - " 5022\n", - " ITGAM\n", + " 5720\n", + " IGF1\n", " NCBI\n", - " 3684\n", + " 3479\n", " gene/protein\n", " interacts with\n", " bioprocess_protein\n", @@ -1717,16 +1564,16 @@ " \n", " \n", "\n", - "

6300 rows × 12 columns

\n", + "

3880 rows × 12 columns

\n", "" ], "text/plain": [ " head_index head_name head_source head_id \\\n", - "6351294 112487 neutrophil degranulation GO 43312 \n", "6351300 112487 neutrophil degranulation GO 43312 \n", - "6351340 112487 neutrophil degranulation GO 43312 \n", - "6351341 112487 neutrophil degranulation GO 43312 \n", "6351346 112487 neutrophil degranulation GO 43312 \n", + "6351457 112487 neutrophil degranulation GO 43312 \n", + "6351710 103224 platelet degranulation GO 2576 \n", + "6351714 103224 platelet degranulation GO 2576 \n", "... ... ... ... ... \n", "3781707 2111 LRRK2 NCBI 120892 \n", "3781708 2111 LRRK2 NCBI 120892 \n", @@ -1735,11 +1582,11 @@ "3781824 34779 NKX2-3 NCBI 159296 \n", "\n", " head_type tail_index \\\n", - "6351294 biological_process 1990 \n", "6351300 biological_process 3333 \n", - "6351340 biological_process 2012 \n", - "6351341 biological_process 3064 \n", "6351346 biological_process 5022 \n", + "6351457 biological_process 12663 \n", + "6351710 biological_process 2057 \n", + "6351714 biological_process 5720 \n", "... ... ... \n", "3781707 gene/protein 51599 \n", "3781708 gene/protein 52358 \n", @@ -1748,11 +1595,11 @@ "3781824 gene/protein 100699 \n", "\n", " tail_name tail_source \\\n", - "6351294 FCGR2A NCBI \n", "6351300 FPR2 NCBI \n", - "6351340 CXCR1 NCBI \n", - "6351341 CXCR2 NCBI \n", "6351346 ITGAM NCBI \n", + "6351457 SLC11A1 NCBI \n", + "6351710 FN1 NCBI \n", + "6351714 IGF1 NCBI \n", "... ... ... \n", "3781707 negative regulation of peroxidase activity GO \n", "3781708 regulation of kidney size GO \n", @@ -1761,11 +1608,11 @@ "3781824 post-embryonic digestive tract morphogenesis GO \n", "\n", " tail_id tail_type display_relation relation \n", - "6351294 2212 gene/protein interacts with bioprocess_protein \n", "6351300 2358 gene/protein interacts with bioprocess_protein \n", - "6351340 3577 gene/protein interacts with bioprocess_protein \n", - "6351341 3579 gene/protein interacts with bioprocess_protein \n", "6351346 3684 gene/protein interacts with bioprocess_protein \n", + "6351457 6556 gene/protein interacts with bioprocess_protein \n", + "6351710 2335 gene/protein interacts with bioprocess_protein \n", + "6351714 3479 gene/protein interacts with bioprocess_protein \n", "... ... ... ... ... \n", "3781707 2000469 biological_process interacts with bioprocess_protein \n", "3781708 35564 biological_process interacts with bioprocess_protein \n", @@ -1773,10 +1620,10 @@ "3781811 38184 biological_process interacts with bioprocess_protein \n", "3781824 48621 biological_process interacts with bioprocess_protein \n", "\n", - "[6300 rows x 12 columns]" + "[3880 rows x 12 columns]" ] }, - "execution_count": 12, + "execution_count": 14, "metadata": {}, "output_type": "execute_result" } @@ -1810,7 +1657,7 @@ }, { "cell_type": "code", - "execution_count": 13, + "execution_count": 15, "metadata": {}, "outputs": [ { @@ -1850,76 +1697,76 @@ " \n", " \n", " \n", - " 6198264\n", - " 54035\n", - " interleukin-1 binding\n", + " 6198366\n", + " 54290\n", + " enzyme binding\n", " GO\n", - " 19966\n", + " 19899\n", " molecular_function\n", - " 1654\n", - " IL1R2\n", + " 2057\n", + " FN1\n", " NCBI\n", - " 7850\n", + " 2335\n", " gene/protein\n", " interacts with\n", " molfunc_protein\n", " \n", " \n", - " 6198359\n", + " 6198442\n", " 54290\n", " enzyme binding\n", " GO\n", " 19899\n", " molecular_function\n", - " 3578\n", - " ECM1\n", + " 989\n", + " PPARG\n", " NCBI\n", - " 1893\n", + " 5468\n", " gene/protein\n", " interacts with\n", " molfunc_protein\n", " \n", " \n", - " 6198366\n", + " 6198634\n", " 54290\n", " enzyme binding\n", " GO\n", " 19899\n", " molecular_function\n", - " 2057\n", - " FN1\n", + " 6229\n", + " NOD2\n", " NCBI\n", - " 2335\n", + " 64127\n", " gene/protein\n", " interacts with\n", " molfunc_protein\n", " \n", " \n", - " 6198442\n", - " 54290\n", - " enzyme binding\n", + " 6198708\n", + " 54671\n", + " protease binding\n", " GO\n", - " 19899\n", + " 2020\n", " molecular_function\n", - " 989\n", - " PPARG\n", + " 2057\n", + " FN1\n", " NCBI\n", - " 5468\n", + " 2335\n", " gene/protein\n", " interacts with\n", " molfunc_protein\n", " \n", " \n", - " 6198462\n", - " 54290\n", - " enzyme binding\n", + " 6198747\n", + " 54671\n", + " protease binding\n", " GO\n", - " 19899\n", + " 2020\n", " molecular_function\n", - " 772\n", - " RELA\n", + " 2329\n", + " TNF\n", " NCBI\n", - " 5970\n", + " 7124\n", " gene/protein\n", " interacts with\n", " molfunc_protein\n", @@ -2016,66 +1863,66 @@ " \n", " \n", "\n", - "

1466 rows × 12 columns

\n", + "

848 rows × 12 columns

\n", "" ], "text/plain": [ - " head_index head_name head_source head_id \\\n", - "6198264 54035 interleukin-1 binding GO 19966 \n", - "6198359 54290 enzyme binding GO 19899 \n", - "6198366 54290 enzyme binding GO 19899 \n", - "6198442 54290 enzyme binding GO 19899 \n", - "6198462 54290 enzyme binding GO 19899 \n", - "... ... ... ... ... \n", - "3553533 6229 NOD2 NCBI 64127 \n", - "3553770 2111 LRRK2 NCBI 120892 \n", - "3553771 2111 LRRK2 NCBI 120892 \n", - "3553773 2111 LRRK2 NCBI 120892 \n", - "3553832 22105 GPBAR1 NCBI 151306 \n", + " head_index head_name head_source head_id head_type \\\n", + "6198366 54290 enzyme binding GO 19899 molecular_function \n", + "6198442 54290 enzyme binding GO 19899 molecular_function \n", + "6198634 54290 enzyme binding GO 19899 molecular_function \n", + "6198708 54671 protease binding GO 2020 molecular_function \n", + "6198747 54671 protease binding GO 2020 molecular_function \n", + "... ... ... ... ... ... \n", + "3553533 6229 NOD2 NCBI 64127 gene/protein \n", + "3553770 2111 LRRK2 NCBI 120892 gene/protein \n", + "3553771 2111 LRRK2 NCBI 120892 gene/protein \n", + "3553773 2111 LRRK2 NCBI 120892 gene/protein \n", + "3553832 22105 GPBAR1 NCBI 151306 gene/protein \n", "\n", - " head_type tail_index \\\n", - "6198264 molecular_function 1654 \n", - "6198359 molecular_function 3578 \n", - "6198366 molecular_function 2057 \n", - "6198442 molecular_function 989 \n", - "6198462 molecular_function 772 \n", - "... ... ... \n", - "3553533 gene/protein 122117 \n", - "3553770 gene/protein 115199 \n", - "3553771 gene/protein 118105 \n", - "3553773 gene/protein 119847 \n", - "3553832 gene/protein 116806 \n", + " tail_index tail_name \\\n", + "6198366 2057 FN1 \n", + "6198442 989 PPARG \n", + "6198634 6229 NOD2 \n", + "6198708 2057 FN1 \n", + "6198747 2329 TNF \n", + "... ... ... \n", + "3553533 122117 muramyl dipeptide binding \n", + "3553770 115199 GTP-dependent protein kinase activity \n", + "3553771 118105 beta-catenin destruction complex binding \n", + "3553773 119847 peroxidase inhibitor activity \n", + "3553832 116806 G protein-coupled bile acid receptor activity \n", "\n", - " tail_name tail_source tail_id \\\n", - "6198264 IL1R2 NCBI 7850 \n", - "6198359 ECM1 NCBI 1893 \n", - "6198366 FN1 NCBI 2335 \n", - "6198442 PPARG NCBI 5468 \n", - "6198462 RELA NCBI 5970 \n", - "... ... ... ... \n", - "3553533 muramyl dipeptide binding GO 32500 \n", - "3553770 GTP-dependent protein kinase activity GO 34211 \n", - "3553771 beta-catenin destruction complex binding GO 1904713 \n", - "3553773 peroxidase inhibitor activity GO 36479 \n", - "3553832 G protein-coupled bile acid receptor activity GO 38182 \n", + " tail_source tail_id tail_type display_relation \\\n", + "6198366 NCBI 2335 gene/protein interacts with \n", + "6198442 NCBI 5468 gene/protein interacts with \n", + "6198634 NCBI 64127 gene/protein interacts with \n", + "6198708 NCBI 2335 gene/protein interacts with \n", + "6198747 NCBI 7124 gene/protein interacts with \n", + "... ... ... ... ... \n", + "3553533 GO 32500 molecular_function interacts with \n", + "3553770 GO 34211 molecular_function interacts with \n", + "3553771 GO 1904713 molecular_function interacts with \n", + "3553773 GO 36479 molecular_function interacts with \n", + "3553832 GO 38182 molecular_function interacts with \n", "\n", - " tail_type display_relation relation \n", - "6198264 gene/protein interacts with molfunc_protein \n", - "6198359 gene/protein interacts with molfunc_protein \n", - "6198366 gene/protein interacts with molfunc_protein \n", - "6198442 gene/protein interacts with molfunc_protein \n", - "6198462 gene/protein interacts with molfunc_protein \n", - "... ... ... ... \n", - "3553533 molecular_function interacts with molfunc_protein \n", - "3553770 molecular_function interacts with molfunc_protein \n", - "3553771 molecular_function interacts with molfunc_protein \n", - "3553773 molecular_function interacts with molfunc_protein \n", - "3553832 molecular_function interacts with molfunc_protein \n", + " relation \n", + "6198366 molfunc_protein \n", + "6198442 molfunc_protein \n", + "6198634 molfunc_protein \n", + "6198708 molfunc_protein \n", + "6198747 molfunc_protein \n", + "... ... \n", + "3553533 molfunc_protein \n", + "3553770 molfunc_protein \n", + "3553771 molfunc_protein \n", + "3553773 molfunc_protein \n", + "3553832 molfunc_protein \n", "\n", - "[1466 rows x 12 columns]" + "[848 rows x 12 columns]" ] }, - "execution_count": 13, + "execution_count": 15, "metadata": {}, "output_type": "execute_result" } @@ -2109,7 +1956,7 @@ }, { "cell_type": "code", - "execution_count": 14, + "execution_count": 16, "metadata": {}, "outputs": [ { @@ -2149,76 +1996,76 @@ " \n", " \n", " \n", - " 6267848\n", - " 126078\n", - " ficolin-1-rich granule lumen\n", + " 6268120\n", + " 124245\n", + " extracellular space\n", " GO\n", - " 1904813\n", + " 5615\n", " cellular_component\n", - " 3474\n", - " MMP9\n", + " 2384\n", + " CRP\n", " NCBI\n", - " 4318\n", + " 1401\n", " gene/protein\n", " interacts with\n", " cellcomp_protein\n", " \n", " \n", - " 6268120\n", + " 6268231\n", " 124245\n", " extracellular space\n", " GO\n", " 5615\n", " cellular_component\n", - " 2384\n", - " CRP\n", + " 2057\n", + " FN1\n", " NCBI\n", - " 1401\n", + " 2335\n", " gene/protein\n", " interacts with\n", " cellcomp_protein\n", " \n", " \n", - " 6268163\n", + " 6268290\n", " 124245\n", " extracellular space\n", " GO\n", " 5615\n", " cellular_component\n", - " 5805\n", - " DEFA5\n", + " 7083\n", + " HLA-DRB1\n", " NCBI\n", - " 1670\n", + " 3123\n", " gene/protein\n", " interacts with\n", " cellcomp_protein\n", " \n", " \n", - " 6268164\n", + " 6268329\n", " 124245\n", " extracellular space\n", " GO\n", " 5615\n", " cellular_component\n", - " 657\n", - " DEFA6\n", + " 3495\n", + " IFNG\n", " NCBI\n", - " 1671\n", + " 3458\n", " gene/protein\n", " interacts with\n", " cellcomp_protein\n", " \n", " \n", - " 6268173\n", + " 6268331\n", " 124245\n", " extracellular space\n", " GO\n", " 5615\n", " cellular_component\n", - " 3578\n", - " ECM1\n", + " 5720\n", + " IGF1\n", " NCBI\n", - " 1893\n", + " 3479\n", " gene/protein\n", " interacts with\n", " cellcomp_protein\n", @@ -2239,31 +2086,31 @@ " ...\n", " \n", " \n", - " 3636708\n", - " 2139\n", - " ARPC2\n", + " 3636360\n", + " 6661\n", + " ATG16L1\n", " NCBI\n", - " 10109\n", + " 55054\n", " gene/protein\n", - " 126261\n", - " muscle cell projection membrane\n", + " 125634\n", + " phagophore assembly site membrane\n", " GO\n", - " 36195\n", + " 34045\n", " cellular_component\n", " interacts with\n", " cellcomp_protein\n", " \n", " \n", - " 3636819\n", - " 9763\n", - " ORMDL3\n", + " 3636472\n", + " 2111\n", + " LRRK2\n", " NCBI\n", - " 94103\n", + " 120892\n", " gene/protein\n", - " 126815\n", - " SPOTS complex\n", + " 127370\n", + " amphisome\n", " GO\n", - " 35339\n", + " 44753\n", " cellular_component\n", " interacts with\n", " cellcomp_protein\n", @@ -2315,66 +2162,66 @@ " \n", " \n", "\n", - "

1348 rows × 12 columns

\n", + "

710 rows × 12 columns

\n", "" ], "text/plain": [ - " head_index head_name head_source head_id \\\n", - "6267848 126078 ficolin-1-rich granule lumen GO 1904813 \n", - "6268120 124245 extracellular space GO 5615 \n", - "6268163 124245 extracellular space GO 5615 \n", - "6268164 124245 extracellular space GO 5615 \n", - "6268173 124245 extracellular space GO 5615 \n", - "... ... ... ... ... \n", - "3636708 2139 ARPC2 NCBI 10109 \n", - "3636819 9763 ORMDL3 NCBI 94103 \n", - "3637211 6661 ATG16L1 NCBI 55054 \n", - "3637234 2111 LRRK2 NCBI 120892 \n", - "3637328 2111 LRRK2 NCBI 120892 \n", + " head_index head_name head_source head_id \\\n", + "6268120 124245 extracellular space GO 5615 \n", + "6268231 124245 extracellular space GO 5615 \n", + "6268290 124245 extracellular space GO 5615 \n", + "6268329 124245 extracellular space GO 5615 \n", + "6268331 124245 extracellular space GO 5615 \n", + "... ... ... ... ... \n", + "3636360 6661 ATG16L1 NCBI 55054 \n", + "3636472 2111 LRRK2 NCBI 120892 \n", + "3637211 6661 ATG16L1 NCBI 55054 \n", + "3637234 2111 LRRK2 NCBI 120892 \n", + "3637328 2111 LRRK2 NCBI 120892 \n", "\n", " head_type tail_index \\\n", - "6267848 cellular_component 3474 \n", "6268120 cellular_component 2384 \n", - "6268163 cellular_component 5805 \n", - "6268164 cellular_component 657 \n", - "6268173 cellular_component 3578 \n", + "6268231 cellular_component 2057 \n", + "6268290 cellular_component 7083 \n", + "6268329 cellular_component 3495 \n", + "6268331 cellular_component 5720 \n", "... ... ... \n", - "3636708 gene/protein 126261 \n", - "3636819 gene/protein 126815 \n", + "3636360 gene/protein 125634 \n", + "3636472 gene/protein 127370 \n", "3637211 gene/protein 126444 \n", "3637234 gene/protein 126938 \n", "3637328 gene/protein 125942 \n", "\n", " tail_name tail_source tail_id \\\n", - "6267848 MMP9 NCBI 4318 \n", "6268120 CRP NCBI 1401 \n", - "6268163 DEFA5 NCBI 1670 \n", - "6268164 DEFA6 NCBI 1671 \n", - "6268173 ECM1 NCBI 1893 \n", + "6268231 FN1 NCBI 2335 \n", + "6268290 HLA-DRB1 NCBI 3123 \n", + "6268329 IFNG NCBI 3458 \n", + "6268331 IGF1 NCBI 3479 \n", "... ... ... ... \n", - "3636708 muscle cell projection membrane GO 36195 \n", - "3636819 SPOTS complex GO 35339 \n", + "3636360 phagophore assembly site membrane GO 34045 \n", + "3636472 amphisome GO 44753 \n", "3637211 vacuole-isolation membrane contact site GO 120095 \n", "3637234 cytoplasmic side of mitochondrial outer membrane GO 32473 \n", "3637328 caveola neck GO 99400 \n", "\n", " tail_type display_relation relation \n", - "6267848 gene/protein interacts with cellcomp_protein \n", "6268120 gene/protein interacts with cellcomp_protein \n", - "6268163 gene/protein interacts with cellcomp_protein \n", - "6268164 gene/protein interacts with cellcomp_protein \n", - "6268173 gene/protein interacts with cellcomp_protein \n", + "6268231 gene/protein interacts with cellcomp_protein \n", + "6268290 gene/protein interacts with cellcomp_protein \n", + "6268329 gene/protein interacts with cellcomp_protein \n", + "6268331 gene/protein interacts with cellcomp_protein \n", "... ... ... ... \n", - "3636708 cellular_component interacts with cellcomp_protein \n", - "3636819 cellular_component interacts with cellcomp_protein \n", + "3636360 cellular_component interacts with cellcomp_protein \n", + "3636472 cellular_component interacts with cellcomp_protein \n", "3637211 cellular_component interacts with cellcomp_protein \n", "3637234 cellular_component interacts with cellcomp_protein \n", "3637328 cellular_component interacts with cellcomp_protein \n", "\n", - "[1348 rows x 12 columns]" + "[710 rows x 12 columns]" ] }, - "execution_count": 14, + "execution_count": 16, "metadata": {}, "output_type": "execute_result" } @@ -2408,7 +2255,7 @@ }, { "cell_type": "code", - "execution_count": 15, + "execution_count": 17, "metadata": {}, "outputs": [ { @@ -2450,15 +2297,15 @@ " \n", " \n", " 0\n", - " 37785\n", - " ulcerative colitis (disease)\n", - " MONDO\n", - " 5101\n", + " 37784\n", + " Crohn disease\n", + " MONDO_grouped\n", + " 5011_5535\n", " disease\n", - " 7359\n", - " ADCY7\n", + " 2384\n", + " CRP\n", " NCBI\n", - " 113\n", + " 1401\n", " gene/protein\n", " associated with\n", " disease_protein\n", @@ -2466,15 +2313,15 @@ " \n", " \n", " 1\n", - " 28158\n", - " inflammatory bowel disease\n", - " MONDO_grouped\n", - " 9960_12845_33643_11471_12831_12875_12941_13153...\n", + " 83770\n", + " Crohn's colitis\n", + " MONDO\n", + " 5532\n", " disease\n", - " 7359\n", - " ADCY7\n", + " 2384\n", + " CRP\n", " NCBI\n", - " 113\n", + " 1401\n", " gene/protein\n", " associated with\n", " disease_protein\n", @@ -2482,15 +2329,15 @@ " \n", " \n", " 2\n", - " 37785\n", - " ulcerative colitis (disease)\n", - " MONDO\n", - " 5101\n", + " 37784\n", + " Crohn disease\n", + " MONDO_grouped\n", + " 5011_5535\n", " disease\n", - " 2874\n", - " PRDM1\n", + " 3088\n", + " DNMT3A\n", " NCBI\n", - " 639\n", + " 1788\n", " gene/protein\n", " associated with\n", " disease_protein\n", @@ -2498,15 +2345,15 @@ " \n", " \n", " 3\n", - " 28158\n", - " inflammatory bowel disease\n", - " MONDO_grouped\n", - " 9960_12845_33643_11471_12831_12875_12941_13153...\n", + " 83770\n", + " Crohn's colitis\n", + " MONDO\n", + " 5532\n", " disease\n", - " 2874\n", - " PRDM1\n", + " 3088\n", + " DNMT3A\n", " NCBI\n", - " 639\n", + " 1788\n", " gene/protein\n", " associated with\n", " disease_protein\n", @@ -2514,15 +2361,15 @@ " \n", " \n", " 4\n", - " 37785\n", - " ulcerative colitis (disease)\n", - " MONDO\n", - " 5101\n", + " 37784\n", + " Crohn disease\n", + " MONDO_grouped\n", + " 5011_5535\n", " disease\n", - " 2712\n", - " CASP3\n", + " 2057\n", + " FN1\n", " NCBI\n", - " 836\n", + " 2335\n", " gene/protein\n", " associated with\n", " disease_protein\n", @@ -2545,39 +2392,39 @@ " ...\n", " \n", " \n", - " 12747\n", - " 2139\n", - " ARPC2\n", + " 7063\n", + " 6661\n", + " ATG16L1\n", " NCBI\n", - " 10109\n", + " 55054\n", " gene/protein\n", - " 126261\n", - " muscle cell projection membrane\n", + " 125634\n", + " phagophore assembly site membrane\n", " GO\n", - " 36195\n", + " 34045\n", " cellular_component\n", " interacts with\n", " cellcomp_protein\n", " (gene/protein, interacts with, cellular_compon...\n", " \n", " \n", - " 12748\n", - " 9763\n", - " ORMDL3\n", + " 7064\n", + " 2111\n", + " LRRK2\n", " NCBI\n", - " 94103\n", + " 120892\n", " gene/protein\n", - " 126815\n", - " SPOTS complex\n", + " 127370\n", + " amphisome\n", " GO\n", - " 35339\n", + " 44753\n", " cellular_component\n", " interacts with\n", " cellcomp_protein\n", " (gene/protein, interacts with, cellular_compon...\n", " \n", " \n", - " 12749\n", + " 7065\n", " 6661\n", " ATG16L1\n", " NCBI\n", @@ -2593,7 +2440,7 @@ " (gene/protein, interacts with, cellular_compon...\n", " \n", " \n", - " 12750\n", + " 7066\n", " 2111\n", " LRRK2\n", " NCBI\n", @@ -2609,7 +2456,7 @@ " (gene/protein, interacts with, cellular_compon...\n", " \n", " \n", - " 12751\n", + " 7067\n", " 2111\n", " LRRK2\n", " NCBI\n", @@ -2626,79 +2473,66 @@ " \n", " \n", "\n", - "

12752 rows × 13 columns

\n", + "

7068 rows × 13 columns

\n", "" ], "text/plain": [ - " head_index head_name head_source \\\n", - "0 37785 ulcerative colitis (disease) MONDO \n", - "1 28158 inflammatory bowel disease MONDO_grouped \n", - "2 37785 ulcerative colitis (disease) MONDO \n", - "3 28158 inflammatory bowel disease MONDO_grouped \n", - "4 37785 ulcerative colitis (disease) MONDO \n", - "... ... ... ... \n", - "12747 2139 ARPC2 NCBI \n", - "12748 9763 ORMDL3 NCBI \n", - "12749 6661 ATG16L1 NCBI \n", - "12750 2111 LRRK2 NCBI \n", - "12751 2111 LRRK2 NCBI \n", - "\n", - " head_id head_type \\\n", - "0 5101 disease \n", - "1 9960_12845_33643_11471_12831_12875_12941_13153... disease \n", - "2 5101 disease \n", - "3 9960_12845_33643_11471_12831_12875_12941_13153... disease \n", - "4 5101 disease \n", - "... ... ... \n", - "12747 10109 gene/protein \n", - "12748 94103 gene/protein \n", - "12749 55054 gene/protein \n", - "12750 120892 gene/protein \n", - "12751 120892 gene/protein \n", + " head_index head_name head_source head_id head_type \\\n", + "0 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", + "1 83770 Crohn's colitis MONDO 5532 disease \n", + "2 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", + "3 83770 Crohn's colitis MONDO 5532 disease \n", + "4 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", + "... ... ... ... ... ... \n", + "7063 6661 ATG16L1 NCBI 55054 gene/protein \n", + "7064 2111 LRRK2 NCBI 120892 gene/protein \n", + "7065 6661 ATG16L1 NCBI 55054 gene/protein \n", + "7066 2111 LRRK2 NCBI 120892 gene/protein \n", + "7067 2111 LRRK2 NCBI 120892 gene/protein \n", "\n", - " tail_index tail_name \\\n", - "0 7359 ADCY7 \n", - "1 7359 ADCY7 \n", - "2 2874 PRDM1 \n", - "3 2874 PRDM1 \n", - "4 2712 CASP3 \n", - "... ... ... \n", - "12747 126261 muscle cell projection membrane \n", - "12748 126815 SPOTS complex \n", - "12749 126444 vacuole-isolation membrane contact site \n", - "12750 126938 cytoplasmic side of mitochondrial outer membrane \n", - "12751 125942 caveola neck \n", + " tail_index tail_name \\\n", + "0 2384 CRP \n", + "1 2384 CRP \n", + "2 3088 DNMT3A \n", + "3 3088 DNMT3A \n", + "4 2057 FN1 \n", + "... ... ... \n", + "7063 125634 phagophore assembly site membrane \n", + "7064 127370 amphisome \n", + "7065 126444 vacuole-isolation membrane contact site \n", + "7066 126938 cytoplasmic side of mitochondrial outer membrane \n", + "7067 125942 caveola neck \n", "\n", - " tail_source tail_id tail_type display_relation \\\n", - "0 NCBI 113 gene/protein associated with \n", - "1 NCBI 113 gene/protein associated with \n", - "2 NCBI 639 gene/protein associated with \n", - "3 NCBI 639 gene/protein associated with \n", - "4 NCBI 836 gene/protein associated with \n", - "... ... ... ... ... \n", - "12747 GO 36195 cellular_component interacts with \n", - "12748 GO 35339 cellular_component interacts with \n", - "12749 GO 120095 cellular_component interacts with \n", - "12750 GO 32473 cellular_component interacts with \n", - "12751 GO 99400 cellular_component interacts with \n", + " tail_source tail_id tail_type display_relation \\\n", + "0 NCBI 1401 gene/protein associated with \n", + "1 NCBI 1401 gene/protein associated with \n", + "2 NCBI 1788 gene/protein associated with \n", + "3 NCBI 1788 gene/protein associated with \n", + "4 NCBI 2335 gene/protein associated with \n", + "... ... ... ... ... \n", + "7063 GO 34045 cellular_component interacts with \n", + "7064 GO 44753 cellular_component interacts with \n", + "7065 GO 120095 cellular_component interacts with \n", + "7066 GO 32473 cellular_component interacts with \n", + "7067 GO 99400 cellular_component interacts with \n", "\n", - " relation edge_type \n", - "0 disease_protein (disease, associated with, gene/protein) \n", - "1 disease_protein (disease, associated with, gene/protein) \n", - "2 disease_protein (disease, associated with, gene/protein) \n", - "3 disease_protein (disease, associated with, gene/protein) \n", - "4 disease_protein (disease, associated with, gene/protein) \n", - "... ... ... \n", - "12747 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", - "12748 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", - "12749 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", - "12750 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", - "12751 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + " relation edge_type \n", + "0 disease_protein (disease, associated with, gene/protein) \n", + "1 disease_protein (disease, associated with, gene/protein) \n", + "2 disease_protein (disease, associated with, gene/protein) \n", + "3 disease_protein (disease, associated with, gene/protein) \n", + "4 disease_protein (disease, associated with, gene/protein) \n", + "... ... ... \n", + "7063 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + "7064 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + "7065 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + "7066 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", + "7067 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", "\n", - "[12752 rows x 13 columns]" + "[7068 rows x 13 columns]" ] }, - "execution_count": 15, + "execution_count": 17, "metadata": {}, "output_type": "execute_result" } @@ -2729,7 +2563,7 @@ }, { "cell_type": "code", - "execution_count": 16, + "execution_count": 18, "metadata": {}, "outputs": [ { @@ -2770,35 +2604,35 @@ " gene/protein\n", " \n", " \n", - " 179\n", - " 179\n", - " IL10RB\n", + " 729\n", + " 729\n", + " STAT3\n", " NCBI\n", - " 3588\n", + " 6774\n", " gene/protein\n", " \n", " \n", - " 192\n", - " 192\n", - " GNA12\n", + " 989\n", + " 989\n", + " PPARG\n", " NCBI\n", - " 2768\n", + " 5468\n", " gene/protein\n", " \n", " \n", - " 279\n", - " 279\n", - " HNF4A\n", + " 1122\n", + " 1122\n", + " PPARA\n", " NCBI\n", - " 3172\n", + " 5465\n", " gene/protein\n", " \n", " \n", - " 417\n", - " 417\n", - " VCAM1\n", + " 1480\n", + " 1480\n", + " ADIPOQ\n", " NCBI\n", - " 7412\n", + " 9370\n", " gene/protein\n", " \n", " \n", @@ -2810,6 +2644,22 @@ " ...\n", " \n", " \n", + " 129310\n", + " 129310\n", + " Potential therapeutics for SARS\n", + " REACTOME\n", + " R-HSA-9679191\n", + " pathway\n", + " \n", + " \n", + " 129355\n", + " 129355\n", + " Detoxification of Reactive Oxygen Species\n", + " REACTOME\n", + " R-HSA-3299685\n", + " pathway\n", + " \n", + " \n", " 129360\n", " 129360\n", " IRAK2 mediated activation of TAK1 complex upon...\n", @@ -2826,14 +2676,6 @@ " pathway\n", " \n", " \n", - " 129365\n", - " 129365\n", - " Antigen processing: Ubiquitination & Proteasom...\n", - " REACTOME\n", - " R-HSA-983168\n", - " pathway\n", - " \n", - " \n", " 129366\n", " 129366\n", " Antigen Presentation: Folding, assembly and pe...\n", @@ -2841,50 +2683,42 @@ " R-HSA-983170\n", " pathway\n", " \n", - " \n", - " 129367\n", - " 129367\n", - " Kinesins\n", - " REACTOME\n", - " R-HSA-983189\n", - " pathway\n", - " \n", " \n", "\n", - "

3426 rows × 5 columns

\n", + "

2079 rows × 5 columns

\n", "" ], "text/plain": [ " node_index node_name \\\n", "144 144 SMAD3 \n", - "179 179 IL10RB \n", - "192 192 GNA12 \n", - "279 279 HNF4A \n", - "417 417 VCAM1 \n", + "729 729 STAT3 \n", + "989 989 PPARG \n", + "1122 1122 PPARA \n", + "1480 1480 ADIPOQ \n", "... ... ... \n", + "129310 129310 Potential therapeutics for SARS \n", + "129355 129355 Detoxification of Reactive Oxygen Species \n", "129360 129360 IRAK2 mediated activation of TAK1 complex upon... \n", "129361 129361 TRAF6 mediated IRF7 activation in TLR7/8 or 9 ... \n", - "129365 129365 Antigen processing: Ubiquitination & Proteasom... \n", "129366 129366 Antigen Presentation: Folding, assembly and pe... \n", - "129367 129367 Kinesins \n", "\n", - " node_source node_id node_type \n", - "144 NCBI 4088 gene/protein \n", - "179 NCBI 3588 gene/protein \n", - "192 NCBI 2768 gene/protein \n", - "279 NCBI 3172 gene/protein \n", - "417 NCBI 7412 gene/protein \n", - "... ... ... ... \n", - "129360 REACTOME R-HSA-975163 pathway \n", - "129361 REACTOME R-HSA-975110 pathway \n", - "129365 REACTOME R-HSA-983168 pathway \n", - "129366 REACTOME R-HSA-983170 pathway \n", - "129367 REACTOME R-HSA-983189 pathway \n", + " node_source node_id node_type \n", + "144 NCBI 4088 gene/protein \n", + "729 NCBI 6774 gene/protein \n", + "989 NCBI 5468 gene/protein \n", + "1122 NCBI 5465 gene/protein \n", + "1480 NCBI 9370 gene/protein \n", + "... ... ... ... \n", + "129310 REACTOME R-HSA-9679191 pathway \n", + "129355 REACTOME R-HSA-3299685 pathway \n", + "129360 REACTOME R-HSA-975163 pathway \n", + "129361 REACTOME R-HSA-975110 pathway \n", + "129366 REACTOME R-HSA-983170 pathway \n", "\n", - "[3426 rows x 5 columns]" + "[2079 rows x 5 columns]" ] }, - "execution_count": 16, + "execution_count": 18, "metadata": {}, "output_type": "execute_result" } @@ -2905,12 +2739,12 @@ }, { "cell_type": "code", - "execution_count": 17, + "execution_count": 20, "metadata": {}, "outputs": [], "source": [ "# Store the IBD-related nodes and edges\n", - "local_dir = '../../../../data/primekg_ibd/'\n", + "local_dir = '../../data/primekg_ibd/'\n", "if not os.path.exists(local_dir):\n", " os.makedirs(local_dir)\n", "primekg_ibd_nodes_df.to_parquet(os.path.join(local_dir, 'primekg_ibd_nodes.parquet'), compression='gzip', index=False)\n", @@ -2919,15 +2753,15 @@ }, { "cell_type": "code", - "execution_count": 18, + "execution_count": 21, "metadata": {}, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ - "Number of IBD-related nodes: 3426\n", - "Number of IBD-related edges: 12752\n" + "Number of IBD-related nodes: 2079\n", + "Number of IBD-related edges: 7068\n" ] } ], @@ -2939,24 +2773,24 @@ }, { "cell_type": "code", - "execution_count": 19, + "execution_count": 22, "metadata": {}, "outputs": [ { "data": { "text/plain": [ "node_type\n", - "biological_process 1642\n", - "cellular_component 207\n", - "disease 7\n", - "drug 835\n", - "gene/protein 103\n", - "molecular_function 324\n", - "pathway 308\n", + "biological_process 1172\n", + "cellular_component 146\n", + "disease 3\n", + "drug 276\n", + "gene/protein 51\n", + "molecular_function 222\n", + "pathway 209\n", "dtype: int64" ] }, - "execution_count": 19, + "execution_count": 22, "metadata": {}, "output_type": "execute_result" } @@ -2968,26 +2802,25 @@ }, { "cell_type": "code", - "execution_count": 20, + "execution_count": 23, "metadata": {}, "outputs": [ { "data": { "text/plain": [ "relation display_relation\n", - "bioprocess_protein interacts with 6300\n", - "cellcomp_protein interacts with 1348\n", - "disease_protein associated with 620\n", - "drug_protein carrier 8\n", - " enzyme 64\n", - " target 776\n", - " transporter 1140\n", - "molfunc_protein interacts with 1466\n", - "pathway_protein interacts with 1030\n", + "bioprocess_protein interacts with 3880\n", + "cellcomp_protein interacts with 710\n", + "disease_protein associated with 290\n", + "drug_protein enzyme 14\n", + " target 538\n", + " transporter 178\n", + "molfunc_protein interacts with 848\n", + "pathway_protein interacts with 610\n", "dtype: int64" ] }, - "execution_count": 20, + "execution_count": 23, "metadata": {}, "output_type": "execute_result" } @@ -2999,35 +2832,33 @@ }, { "cell_type": "code", - "execution_count": 21, + "execution_count": 24, "metadata": {}, "outputs": [ { "data": { "text/plain": [ "edge_type\n", - "(biological_process, interacts with, gene/protein) 3150\n", - "(cellular_component, interacts with, gene/protein) 674\n", - "(disease, associated with, gene/protein) 310\n", - "(drug, carrier, gene/protein) 4\n", - "(drug, enzyme, gene/protein) 32\n", - "(drug, target, gene/protein) 388\n", - "(drug, transporter, gene/protein) 570\n", - "(gene/protein, associated with, disease) 310\n", - "(gene/protein, carrier, drug) 4\n", - "(gene/protein, enzyme, drug) 32\n", - "(gene/protein, interacts with, biological_process) 3150\n", - "(gene/protein, interacts with, cellular_component) 674\n", - "(gene/protein, interacts with, molecular_function) 733\n", - "(gene/protein, interacts with, pathway) 515\n", - "(gene/protein, target, drug) 388\n", - "(gene/protein, transporter, drug) 570\n", - "(molecular_function, interacts with, gene/protein) 733\n", - "(pathway, interacts with, gene/protein) 515\n", + "(biological_process, interacts with, gene/protein) 1940\n", + "(cellular_component, interacts with, gene/protein) 355\n", + "(disease, associated with, gene/protein) 145\n", + "(drug, enzyme, gene/protein) 7\n", + "(drug, target, gene/protein) 269\n", + "(drug, transporter, gene/protein) 89\n", + "(gene/protein, associated with, disease) 145\n", + "(gene/protein, enzyme, drug) 7\n", + "(gene/protein, interacts with, biological_process) 1940\n", + "(gene/protein, interacts with, cellular_component) 355\n", + "(gene/protein, interacts with, molecular_function) 424\n", + "(gene/protein, interacts with, pathway) 305\n", + "(gene/protein, target, drug) 269\n", + "(gene/protein, transporter, drug) 89\n", + "(molecular_function, interacts with, gene/protein) 424\n", + "(pathway, interacts with, gene/protein) 305\n", "dtype: int64" ] }, - "execution_count": 21, + "execution_count": 24, "metadata": {}, "output_type": "execute_result" } @@ -3059,7 +2890,7 @@ }, { "cell_type": "code", - "execution_count": 33, + "execution_count": 26, "metadata": {}, "outputs": [ { @@ -3067,14 +2898,14 @@ "output_type": "stream", "text": [ "Loading StarkQAPrimeKG dataset...\n", - "../../../../data/starkqa_primekg/qa/prime/stark_qa/stark_qa.csv already exists. Loading the data from the local directory.\n", + "../../data/starkqa_primekg/qa/prime/stark_qa/stark_qa.csv already exists. Loading the data from the local directory.\n", "Loading StarkQAPrimeKG embeddings...\n" ] } ], "source": [ "# Define starkqa primekg data by providing a local directory where the data is stored\n", - "starkqa_data = StarkQAPrimeKG(local_dir=\"../../../../data/starkqa_primekg/\")\n", + "starkqa_data = StarkQAPrimeKG(local_dir=\"../../data/starkqa_primekg/\")\n", "\n", "# Invoke a method to load the data\n", "starkqa_data.load_data()\n", @@ -3095,7 +2926,7 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 27, "metadata": {}, "outputs": [], "source": [ @@ -3142,9 +2973,203 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 28, "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/tmp/ipykernel_1377/2873064541.py:3: SettingWithCopyWarning: \n", + "A value is trying to be set on a copy of a slice from a DataFrame.\n", + "Try using .loc[row_indexer,col_indexer] = value instead\n", + "\n", + "See the caveats in the documentation: https://pandas.pydata.org/pandas-docs/stable/user_guide/indexing.html#returning-a-view-versus-a-copy\n", + " primekg_ibd_nodes_df['enriched_node'] = text_enriched_nodes\n" + ] + }, + { + "data": { + "text/html": [ + "
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node_indexnode_namenode_sourcenode_idnode_typeenriched_node
144144SMAD3NCBI4088gene/proteinSMAD3 belongs to gene/protein category. The SM...
729729STAT3NCBI6774gene/proteinSTAT3 belongs to gene/protein category. The pr...
989989PPARGNCBI5468gene/proteinPPARG belongs to gene/protein category. This g...
11221122PPARANCBI5465gene/proteinPPARA belongs to gene/protein category. Peroxi...
14801480ADIPOQNCBI9370gene/proteinADIPOQ belongs to gene/protein category. This ...
.....................
129310129310Potential therapeutics for SARSREACTOMER-HSA-9679191pathwayPotential therapeutics for SARS belongs to pat...
129355129355Detoxification of Reactive Oxygen SpeciesREACTOMER-HSA-3299685pathwayDetoxification of Reactive Oxygen Species belo...
129360129360IRAK2 mediated activation of TAK1 complex upon...REACTOMER-HSA-975163pathwayIRAK2 mediated activation of TAK1 complex upon...
129361129361TRAF6 mediated IRF7 activation in TLR7/8 or 9 ...REACTOMER-HSA-975110pathwayTRAF6 mediated IRF7 activation in TLR7/8 or 9 ...
129366129366Antigen Presentation: Folding, assembly and pe...REACTOMER-HSA-983170pathwayAntigen Presentation: Folding, assembly and pe...
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2079 rows × 6 columns

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" + ], + "text/plain": [ + " node_index node_name \\\n", + "144 144 SMAD3 \n", + "729 729 STAT3 \n", + "989 989 PPARG \n", + "1122 1122 PPARA \n", + "1480 1480 ADIPOQ \n", + "... ... ... \n", + "129310 129310 Potential therapeutics for SARS \n", + "129355 129355 Detoxification of Reactive Oxygen Species \n", + "129360 129360 IRAK2 mediated activation of TAK1 complex upon... \n", + "129361 129361 TRAF6 mediated IRF7 activation in TLR7/8 or 9 ... \n", + "129366 129366 Antigen Presentation: Folding, assembly and pe... \n", + "\n", + " node_source node_id node_type \\\n", + "144 NCBI 4088 gene/protein \n", + "729 NCBI 6774 gene/protein \n", + "989 NCBI 5468 gene/protein \n", + "1122 NCBI 5465 gene/protein \n", + "1480 NCBI 9370 gene/protein \n", + "... ... ... ... \n", + "129310 REACTOME R-HSA-9679191 pathway \n", + "129355 REACTOME R-HSA-3299685 pathway \n", + "129360 REACTOME R-HSA-975163 pathway \n", + "129361 REACTOME R-HSA-975110 pathway \n", + "129366 REACTOME R-HSA-983170 pathway \n", + "\n", + " enriched_node \n", + "144 SMAD3 belongs to gene/protein category. The SM... \n", + "729 STAT3 belongs to gene/protein category. The pr... \n", + "989 PPARG belongs to gene/protein category. This g... \n", + "1122 PPARA belongs to gene/protein category. Peroxi... \n", + "1480 ADIPOQ belongs to gene/protein category. This ... \n", + "... ... \n", + "129310 Potential therapeutics for SARS belongs to pat... \n", + "129355 Detoxification of Reactive Oxygen Species belo... \n", + "129360 IRAK2 mediated activation of TAK1 complex upon... \n", + "129361 TRAF6 mediated IRF7 activation in TLR7/8 or 9 ... \n", + "129366 Antigen Presentation: Folding, assembly and pe... \n", + "\n", + "[2079 rows x 6 columns]" + ] + }, + "execution_count": 28, + "metadata": {}, + "output_type": "execute_result" + } + ], "source": [ "# Perform node enrichment for each row in primekg_nodes\n", "text_enriched_nodes = primekg_ibd_nodes_df.apply(lambda x: do_enrichment_text(x, starkqa_node_info[x['node_index']]), axis=1).tolist()\n", @@ -3163,9 +3188,171 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 29, "metadata": {}, - "outputs": [], + "outputs": [ + { + "data": { + "text/html": [ + "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelationedge_typeenriched_edge
037784Crohn diseaseMONDO_grouped5011_5535disease2384CRPNCBI1401gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn disease (disease) has a direct relations...
183770Crohn's colitisMONDO5532disease2384CRPNCBI1401gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn's colitis (disease) has a direct relatio...
237784Crohn diseaseMONDO_grouped5011_5535disease3088DNMT3ANCBI1788gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn disease (disease) has a direct relations...
383770Crohn's colitisMONDO5532disease3088DNMT3ANCBI1788gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn's colitis (disease) has a direct relatio...
437784Crohn diseaseMONDO_grouped5011_5535disease2057FN1NCBI2335gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn disease (disease) has a direct relations...
\n", + "
" + ], + "text/plain": [ + " head_index head_name head_source head_id head_type \\\n", + "0 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", + "1 83770 Crohn's colitis MONDO 5532 disease \n", + "2 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", + "3 83770 Crohn's colitis MONDO 5532 disease \n", + "4 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", + "\n", + " tail_index tail_name tail_source tail_id tail_type display_relation \\\n", + "0 2384 CRP NCBI 1401 gene/protein associated with \n", + "1 2384 CRP NCBI 1401 gene/protein associated with \n", + "2 3088 DNMT3A NCBI 1788 gene/protein associated with \n", + "3 3088 DNMT3A NCBI 1788 gene/protein associated with \n", + "4 2057 FN1 NCBI 2335 gene/protein associated with \n", + "\n", + " relation edge_type \\\n", + "0 disease_protein (disease, associated with, gene/protein) \n", + "1 disease_protein (disease, associated with, gene/protein) \n", + "2 disease_protein (disease, associated with, gene/protein) \n", + "3 disease_protein (disease, associated with, gene/protein) \n", + "4 disease_protein (disease, associated with, gene/protein) \n", + "\n", + " enriched_edge \n", + "0 Crohn disease (disease) has a direct relations... \n", + "1 Crohn's colitis (disease) has a direct relatio... \n", + "2 Crohn disease (disease) has a direct relations... \n", + "3 Crohn's colitis (disease) has a direct relatio... \n", + "4 Crohn disease (disease) has a direct relations... " + ] + }, + "execution_count": 29, + "metadata": {}, + "output_type": "execute_result" + } + ], "source": [ "# Perform textual enrichment over the edges by simply concatenating the head and tail nodes with the relation followed by the enriched node information\n", "text_enriched_edges = primekg_ibd_edges_df.apply(lambda x: f\"{x['head_name']} ({x['head_type']}) has a direct relationship of {x['relation']}:{x['display_relation']} with {x['tail_name']} ({x['tail_type']}).\", axis=1).tolist()\n", @@ -3191,9 +3378,30 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 30, "metadata": {}, - "outputs": [], + "outputs": [ + { + "ename": "ValueError", + "evalue": "Error: Failed to connect to Ollama. Please check that Ollama is downloaded, running and accessible. https://ollama.com/download and restarted Ollama server.", + "output_type": "error", + "traceback": [ + "\u001b[0;31m---------------------------------------------------------------------------\u001b[0m", + "\u001b[0;31mConnectionError\u001b[0m Traceback (most recent call last)", + "File \u001b[0;32m~/FORK-AIAgents4Pharma/AIAgents4Pharma/notebook/../aiagents4pharma/talk2knowledgegraphs/utils/embeddings/ollama.py:40\u001b[0m, in \u001b[0;36mEmbeddingWithOllama.__setup\u001b[0;34m(self, model_name)\u001b[0m\n\u001b[1;32m 39\u001b[0m \u001b[38;5;28;01mtry\u001b[39;00m:\n\u001b[0;32m---> 40\u001b[0m models_list \u001b[38;5;241m=\u001b[39m \u001b[43mollama\u001b[49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mlist\u001b[49m\u001b[43m(\u001b[49m\u001b[43m)\u001b[49m[\u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mmodels\u001b[39m\u001b[38;5;124m\"\u001b[39m]\n\u001b[1;32m 41\u001b[0m \u001b[38;5;28;01mif\u001b[39;00m model_name \u001b[38;5;129;01mnot\u001b[39;00m \u001b[38;5;129;01min\u001b[39;00m [m[\u001b[38;5;124m'\u001b[39m\u001b[38;5;124mmodel\u001b[39m\u001b[38;5;124m'\u001b[39m]\u001b[38;5;241m.\u001b[39mreplace(\u001b[38;5;124m\"\u001b[39m\u001b[38;5;124m:latest\u001b[39m\u001b[38;5;124m\"\u001b[39m, \u001b[38;5;124m\"\u001b[39m\u001b[38;5;124m\"\u001b[39m) \u001b[38;5;28;01mfor\u001b[39;00m m \u001b[38;5;129;01min\u001b[39;00m models_list]:\n", + "File \u001b[0;32m~/miniconda3/envs/py311/lib/python3.11/site-packages/ollama/_client.py:567\u001b[0m, in \u001b[0;36mClient.list\u001b[0;34m(self)\u001b[0m\n\u001b[1;32m 566\u001b[0m \u001b[38;5;28;01mdef\u001b[39;00m\u001b[38;5;250m \u001b[39m\u001b[38;5;21mlist\u001b[39m(\u001b[38;5;28mself\u001b[39m) \u001b[38;5;241m-\u001b[39m\u001b[38;5;241m>\u001b[39m ListResponse:\n\u001b[0;32m--> 567\u001b[0m \u001b[38;5;28;01mreturn\u001b[39;00m \u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43m_request\u001b[49m\u001b[43m(\u001b[49m\n\u001b[1;32m 568\u001b[0m \u001b[43m \u001b[49m\u001b[43mListResponse\u001b[49m\u001b[43m,\u001b[49m\n\u001b[1;32m 569\u001b[0m \u001b[43m \u001b[49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[38;5;124;43mGET\u001b[39;49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[43m,\u001b[49m\n\u001b[1;32m 570\u001b[0m \u001b[43m \u001b[49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[38;5;124;43m/api/tags\u001b[39;49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[43m,\u001b[49m\n\u001b[1;32m 571\u001b[0m \u001b[43m \u001b[49m\u001b[43m)\u001b[49m\n", + "File \u001b[0;32m~/miniconda3/envs/py311/lib/python3.11/site-packages/ollama/_client.py:178\u001b[0m, in \u001b[0;36mClient._request\u001b[0;34m(self, cls, stream, *args, **kwargs)\u001b[0m\n\u001b[1;32m 176\u001b[0m \u001b[38;5;28;01mreturn\u001b[39;00m inner()\n\u001b[0;32m--> 178\u001b[0m \u001b[38;5;28;01mreturn\u001b[39;00m \u001b[38;5;28mcls\u001b[39m(\u001b[38;5;241m*\u001b[39m\u001b[38;5;241m*\u001b[39m\u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43m_request_raw\u001b[49m\u001b[43m(\u001b[49m\u001b[38;5;241;43m*\u001b[39;49m\u001b[43margs\u001b[49m\u001b[43m,\u001b[49m\u001b[43m \u001b[49m\u001b[38;5;241;43m*\u001b[39;49m\u001b[38;5;241;43m*\u001b[39;49m\u001b[43mkwargs\u001b[49m\u001b[43m)\u001b[49m\u001b[38;5;241m.\u001b[39mjson())\n", + "File \u001b[0;32m~/miniconda3/envs/py311/lib/python3.11/site-packages/ollama/_client.py:124\u001b[0m, in \u001b[0;36mClient._request_raw\u001b[0;34m(self, *args, **kwargs)\u001b[0m\n\u001b[1;32m 123\u001b[0m \u001b[38;5;28;01mexcept\u001b[39;00m httpx\u001b[38;5;241m.\u001b[39mConnectError:\n\u001b[0;32m--> 124\u001b[0m \u001b[38;5;28;01mraise\u001b[39;00m \u001b[38;5;167;01mConnectionError\u001b[39;00m(CONNECTION_ERROR_MESSAGE) \u001b[38;5;28;01mfrom\u001b[39;00m\u001b[38;5;250m \u001b[39m\u001b[38;5;28;01mNone\u001b[39;00m\n", + "\u001b[0;31mConnectionError\u001b[0m: Failed to connect to Ollama. Please check that Ollama is downloaded, running and accessible. https://ollama.com/download", + "\nThe above exception was the direct cause of the following exception:\n", + "\u001b[0;31mValueError\u001b[0m Traceback (most recent call last)", + "Cell \u001b[0;32mIn[30], line 2\u001b[0m\n\u001b[1;32m 1\u001b[0m \u001b[38;5;66;03m# Using nomic-ai/nomic-embed-text-v1.5 model\u001b[39;00m\n\u001b[0;32m----> 2\u001b[0m emb_model \u001b[38;5;241m=\u001b[39m \u001b[43mEmbeddingWithOllama\u001b[49m\u001b[43m(\u001b[49m\u001b[43mmodel_name\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[38;5;124;43mnomic-embed-text\u001b[39;49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[43m)\u001b[49m\n", + "File \u001b[0;32m~/FORK-AIAgents4Pharma/AIAgents4Pharma/notebook/../aiagents4pharma/talk2knowledgegraphs/utils/embeddings/ollama.py:24\u001b[0m, in \u001b[0;36mEmbeddingWithOllama.__init__\u001b[0;34m(self, model_name)\u001b[0m\n\u001b[1;32m 17\u001b[0m \u001b[38;5;250m\u001b[39m\u001b[38;5;124;03m\"\"\"\u001b[39;00m\n\u001b[1;32m 18\u001b[0m \u001b[38;5;124;03mInitialize the EmbeddingWithOllama class.\u001b[39;00m\n\u001b[1;32m 19\u001b[0m \n\u001b[1;32m 20\u001b[0m \u001b[38;5;124;03mArgs:\u001b[39;00m\n\u001b[1;32m 21\u001b[0m \u001b[38;5;124;03m model_name: The name of the Ollama model to be used.\u001b[39;00m\n\u001b[1;32m 22\u001b[0m \u001b[38;5;124;03m\"\"\"\u001b[39;00m\n\u001b[1;32m 23\u001b[0m \u001b[38;5;66;03m# Setup the Ollama server\u001b[39;00m\n\u001b[0;32m---> 24\u001b[0m \u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43m__setup\u001b[49m\u001b[43m(\u001b[49m\u001b[43mmodel_name\u001b[49m\u001b[43m)\u001b[49m\n\u001b[1;32m 26\u001b[0m \u001b[38;5;66;03m# Set parameters\u001b[39;00m\n\u001b[1;32m 27\u001b[0m \u001b[38;5;28mself\u001b[39m\u001b[38;5;241m.\u001b[39mmodel_name \u001b[38;5;241m=\u001b[39m model_name\n", + "File \u001b[0;32m~/FORK-AIAgents4Pharma/AIAgents4Pharma/notebook/../aiagents4pharma/talk2knowledgegraphs/utils/embeddings/ollama.py:50\u001b[0m, in \u001b[0;36mEmbeddingWithOllama.__setup\u001b[0;34m(self, model_name)\u001b[0m\n\u001b[1;32m 46\u001b[0m \u001b[38;5;28;01mwith\u001b[39;00m subprocess\u001b[38;5;241m.\u001b[39mPopen(\n\u001b[1;32m 47\u001b[0m \u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mollama serve\u001b[39m\u001b[38;5;124m\"\u001b[39m, shell\u001b[38;5;241m=\u001b[39m\u001b[38;5;28;01mTrue\u001b[39;00m, stdout\u001b[38;5;241m=\u001b[39msubprocess\u001b[38;5;241m.\u001b[39mPIPE, stderr\u001b[38;5;241m=\u001b[39msubprocess\u001b[38;5;241m.\u001b[39mPIPE\n\u001b[1;32m 48\u001b[0m ):\n\u001b[1;32m 49\u001b[0m time\u001b[38;5;241m.\u001b[39msleep(\u001b[38;5;241m10\u001b[39m)\n\u001b[0;32m---> 50\u001b[0m \u001b[38;5;28;01mraise\u001b[39;00m \u001b[38;5;167;01mValueError\u001b[39;00m(\u001b[38;5;124mf\u001b[39m\u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mError: \u001b[39m\u001b[38;5;132;01m{\u001b[39;00me\u001b[38;5;132;01m}\u001b[39;00m\u001b[38;5;124m and restarted Ollama server.\u001b[39m\u001b[38;5;124m\"\u001b[39m) \u001b[38;5;28;01mfrom\u001b[39;00m\u001b[38;5;250m \u001b[39m\u001b[38;5;21;01me\u001b[39;00m\n", + "\u001b[0;31mValueError\u001b[0m: Error: Failed to connect to Ollama. Please check that Ollama is downloaded, running and accessible. https://ollama.com/download and restarted Ollama server." + ] + } + ], "source": [ "# Using nomic-ai/nomic-embed-text-v1.5 model\n", "emb_model = EmbeddingWithOllama(model_name='nomic-embed-text')" @@ -3494,6 +3702,41 @@ " pickle.dump({\"nodes\": nodes_df, \"edges\": edges_df}, f)" ] }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [] + }, + { + "cell_type": "code", + "execution_count": null, + "metadata": {}, + "outputs": [], + "source": [] + }, { "cell_type": "code", "execution_count": null, From 6579490d069f46fa3de2f5587a3936e6835e60f1 Mon Sep 17 00:00:00 2001 From: ShengZhaoDE Date: Fri, 7 Mar 2025 13:15:23 +0100 Subject: [PATCH 09/14] update rests --- notebook/pdf_keywords.txt | 2 +- notebook/sbml_rag_notebook.ipynb | 208 +++++++++- notebook/species_backgrounds.csv | 648 +++++++++++++++++++++++++++++++ 3 files changed, 839 insertions(+), 19 deletions(-) create mode 100644 notebook/species_backgrounds.csv diff --git a/notebook/pdf_keywords.txt b/notebook/pdf_keywords.txt index 316e0ffa..353054ab 100644 --- a/notebook/pdf_keywords.txt +++ b/notebook/pdf_keywords.txt @@ -1 +1 @@ -Crohns disease, IL-6, T-cells, apoptosis, inflammation, IL-6Rα, sIL-6Rα, gp130, Jak, STAT3, CRP, hepatocytes, leukocytes, sgp130, tocilizumab, GI tract, liver, monoclonal antibodies, SOCS, circulation \ No newline at end of file +Crohns disease, IL-6, IL-6R, sIL-6R, CRP, gp130, Jak, STAT3, T-cells, hepatocytes, apoptosis, inflammation, GI tract, sgp130, tocilizumab, cytokines, Janus kinase, lamina propria, leukocytes, chemokine \ No newline at end of file diff --git a/notebook/sbml_rag_notebook.ipynb b/notebook/sbml_rag_notebook.ipynb index a07aa4e0..5c7f2cef 100644 --- a/notebook/sbml_rag_notebook.ipynb +++ b/notebook/sbml_rag_notebook.ipynb @@ -25,7 +25,7 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 1, "metadata": {}, "outputs": [], "source": [ @@ -42,7 +42,7 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 2, "metadata": {}, "outputs": [], "source": [ @@ -64,7 +64,7 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 3, "metadata": {}, "outputs": [], "source": [ @@ -97,16 +97,32 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 4, "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Analyzing SBML model species...\n", + "Found 44 species in the model\n", + "Species are distributed across 4 compartments\n", + "Loading and processing PDF...\n", + "Extracting keywords from PDF...\n", + "Parsing SBML model for species...\n", + "Limiting processing to 1 species (out of 44 total)\n", + "Extracting background information for 1 species...\n", + "Processing species 1/1: IL6\n" + ] + } + ], "source": [ "# Process the SBML model and PDF\n", "species_backgrounds, keywords, species_stats = process_sbml_and_pdf(\n", " sbml_file_path=sbml_file_path,\n", " pdf_file_path=pdf_file_path,\n", " api_key=openai_api_key,\n", - " max_species=1\n", + " max_species=44\n", ")" ] }, @@ -121,9 +137,37 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 5, "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "PDF Keywords:\n", + "1. Crohns disease\n", + "2. IL-6\n", + "3. T-cells\n", + "4. apoptosis\n", + "5. inflammation\n", + "6. IL-6Rα\n", + "7. sIL-6Rα\n", + "8. gp130\n", + "9. Jak\n", + "10. STAT3\n", + "11. CRP\n", + "12. hepatocytes\n", + "13. leukocytes\n", + "14. sgp130\n", + "15. tocilizumab\n", + "16. GI tract\n", + "17. liver\n", + "18. monoclonal antibodies\n", + "19. SOCS\n", + "20. circulation\n" + ] + } + ], "source": [ "print(\"PDF Keywords:\")\n", "for i, keyword in enumerate(keywords, 1):\n", @@ -139,9 +183,66 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 6, "metadata": {}, - "outputs": [], + "outputs": [ + { + "data": { + "text/html": [ + "
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idnameoriginal_namecompartmentbackground
0mwf626e95e_543f_41e4_aad4_c6bf60ab345bIL6IL6mw53ffe9e6_beef_45c4_90a5_a79197ed506eIL6, or Interleukin 6, is a cytokine that play...
\n", + "
" + ], + "text/plain": [ + " id name original_name \\\n", + "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 IL6 \n", + "\n", + " compartment \\\n", + "0 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "\n", + " background \n", + "0 IL6, or Interleukin 6, is a cytokine that play... " + ] + }, + "execution_count": 6, + "metadata": {}, + "output_type": "execute_result" + } + ], "source": [ "# Create a DataFrame for better visualization\n", "species_df = pd.DataFrame(species_backgrounds)\n", @@ -157,9 +258,27 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 7, "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "\n", + "================================================================================\n", + "1. IL6 (ID: mwf626e95e_543f_41e4_aad4_c6bf60ab345b)\n", + "================================================================================\n", + "IL6, or Interleukin 6, is a cytokine that plays a significant role in the immune system. It is particularly important in the context of Crohn's disease, as it contributes to enhanced T-cell survival and apoptosis resistance in the lamina propria, along with increased chemokine secretion. IL-6 signaling occurs through two pathways: the classical pathway mediated by the membrane-bound IL-6 receptor (IL-6Rα) and the trans-signaling pathway mediated by the soluble IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of the gp130 coreceptor to form a receptor complex that initiates downstream signaling cascades.\n", + "\n", + "The active hexameric IL-6 receptor complex leads to the phosphorylation of gp130-bound Janus kinase (Jak) family proteins and subsequent activation of signal transducer and activator of transcription 3 (STAT3) via phosphorylation. This signaling is implicated in inflammation and autoimmunity processes, which are central to the pathology of Crohn's disease. \n", + "\n", + "Additionally, the model discussed in the provided context focuses on the pharmacokinetics and dynamics of anti–IL-6 and anti–IL-6Rα antibodies, such as tocilizumab, used in the treatment of autoimmune diseases like rheumatoid arthritis. These antibodies target the IL-6 pathways, particularly affecting how IL-6 signaling is modulated, and the model attempts to understand the therapeutic impact and dosing regimens of these biologics.\n", + "\n", + "Overall, IL6 is critical in immune regulation and is a key target for therapeutic intervention in diseases characterized by dysregulated immune responses.\n" + ] + } + ], "source": [ "# Display detailed information for each species\n", "for i, species in enumerate(species_backgrounds, 1):\n", @@ -176,9 +295,17 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 8, "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Results saved to 'species_backgrounds.csv' and 'pdf_keywords.txt'\n" + ] + } + ], "source": [ "# Save species background information to CSV\n", "species_df.to_csv(\"species_backgrounds.csv\", index=False)\n", @@ -201,9 +328,24 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 9, "metadata": {}, - "outputs": [], + "outputs": [ + { + "data": { + "text/plain": [ + "[{'id': 'mwf626e95e_543f_41e4_aad4_c6bf60ab345b',\n", + " 'name': 'IL6',\n", + " 'original_name': 'IL6',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': \"IL6, or Interleukin 6, is a cytokine that plays a significant role in the immune system. It is particularly important in the context of Crohn's disease, as it contributes to enhanced T-cell survival and apoptosis resistance in the lamina propria, along with increased chemokine secretion. IL-6 signaling occurs through two pathways: the classical pathway mediated by the membrane-bound IL-6 receptor (IL-6Rα) and the trans-signaling pathway mediated by the soluble IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of the gp130 coreceptor to form a receptor complex that initiates downstream signaling cascades.\\n\\nThe active hexameric IL-6 receptor complex leads to the phosphorylation of gp130-bound Janus kinase (Jak) family proteins and subsequent activation of signal transducer and activator of transcription 3 (STAT3) via phosphorylation. This signaling is implicated in inflammation and autoimmunity processes, which are central to the pathology of Crohn's disease. \\n\\nAdditionally, the model discussed in the provided context focuses on the pharmacokinetics and dynamics of anti–IL-6 and anti–IL-6Rα antibodies, such as tocilizumab, used in the treatment of autoimmune diseases like rheumatoid arthritis. These antibodies target the IL-6 pathways, particularly affecting how IL-6 signaling is modulated, and the model attempts to understand the therapeutic impact and dosing regimens of these biologics.\\n\\nOverall, IL6 is critical in immune regulation and is a key target for therapeutic intervention in diseases characterized by dysregulated immune responses.\"}]" + ] + }, + "execution_count": 9, + "metadata": {}, + "output_type": "execute_result" + } + ], "source": [ "# List 1: Species background knowledge\n", "species_backgrounds" @@ -211,9 +353,39 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 10, "metadata": {}, - "outputs": [], + "outputs": [ + { + "data": { + "text/plain": [ + "['Crohns disease',\n", + " 'IL-6',\n", + " 'T-cells',\n", + " 'apoptosis',\n", + " 'inflammation',\n", + " 'IL-6Rα',\n", + " 'sIL-6Rα',\n", + " 'gp130',\n", + " 'Jak',\n", + " 'STAT3',\n", + " 'CRP',\n", + " 'hepatocytes',\n", + " 'leukocytes',\n", + " 'sgp130',\n", + " 'tocilizumab',\n", + " 'GI tract',\n", + " 'liver',\n", + " 'monoclonal antibodies',\n", + " 'SOCS',\n", + " 'circulation']" + ] + }, + "execution_count": 10, + "metadata": {}, + "output_type": "execute_result" + } + ], "source": [ "# List 2: PDF keywords\n", "keywords" diff --git a/notebook/species_backgrounds.csv b/notebook/species_backgrounds.csv new file mode 100644 index 00000000..4ae8e0fb --- /dev/null +++ b/notebook/species_backgrounds.csv @@ -0,0 +1,648 @@ +id,name,original_name,compartment,background +mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The provided context outlines the biological function and role of IL-6, a cytokine important in the immune system. Based on the information: + +1. **Biological Function**: + IL-6 is a cytokine involved in immune regulation. It plays a crucial role in enhancing T-cell survival and resistance to apoptosis, particularly in the context of Crohn’s Disease, as well as in promoting chemokine secretion. + +2. **Role in Pathways**: + IL-6 signaling can proceed via two distinct pathways: + - The classical pathway, which involves the membrane-bound IL-6 receptor (IL-6Rα). + - The trans-signaling pathway, which involves a soluble IL-6 receptor (sIL-6Rα). In both pathways, IL-6 forms a complex with its respective receptor, which then recruits the gp130 coreceptor, leading to the formation of a hexameric receptor complex. This complex initiates phosphorylation of gp130-bound Janus kinase (Jak) proteins and subsequent activation of STAT3 (Signal Transducer and Activator of Transcription 3). + +3. **Interactions with Other Molecules**: + IL-6 interacts with its membrane-bound and soluble receptors to initiate signaling. The interaction sequence involves IL-6 binding to IL-6Rα, recruiting gp130, and activating downstream signaling molecules like Jak family proteins and STAT3. + +4. **Importance in the Biological System Being Modeled**: + IL-6 is highlighted as a significant contributor in the pathophysiology of Crohn’s Disease due to its roles in promoting immune cell activities that lead to inflammation. The ability of IL-6 to engage in both classical and trans-signaling pathways suggests it is a versatile mediator in inflammatory processes, making it a critical target for therapeutic interventions. + +5. **General Knowledge and Inference**: + Beyond the context, IL-6 is generally known to be involved in inflammation and is a key player in various inflammatory diseases. It is a target for drugs like tocilizumab, which inhibit IL-6 signaling by preventing the interaction of IL-6 with its receptor, thus being an important therapeutic strategy in diseases such as rheumatoid arthritis. + +In summary, IL-6 is a multifunctional cytokine central to immune regulation and inflammation, making it a crucial element in disease models, particularly those addressing inflammatory conditions like Crohn's Disease." +mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130,sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the context provided, sgp130 is a biological molecule that plays a role in inhibiting IL-6 trans-signaling. Here is a summary of its background information: + +1. **Biological Function**: sgp130 is derived from the extracellular portion of the gp130 protein. It serves to inhibit the signaling pathway of interleukin-6 (IL-6) by binding to the IL-6/sIL-6Rα complex, thereby preventing it from activating downstream signaling pathways. This inhibition is achieved by a fusion protein called sgp130Fc, which combines sgp130 with the Fc region of human IgG1. + +2. **Role in Pathways**: sgp130 influences the IL-6 signaling pathway, specifically targeting the trans-signaling aspect. IL-6 is a pro-inflammatory cytokine that can signal through a complex with soluble IL-6 receptor (sIL-6Rα) and gp130. By interfering with this pathway, sgp130 can modulate inflammatory responses. + +3. **Interactions with Other Molecules**: The primary interaction of sgp130 is with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 inhibits its ability to signal through the cell surface-bound gp130, thus blocking IL-6 mediated effects. The interaction between sgp130 and the IL-6/sIL-6Rα complex is central to its function. + +4. **Importance in the Biological System Being Modeled**: While sgp130 can effectively inhibit IL-6 trans-signaling, the context indicates that its role in the system being modeled is limited. The sensitivity analysis within the model shows that alterations in sgp130 levels have minimal effects on the steady-state values of output parameters due to the high baseline level of sgp130 compared to the relatively low concentration of free IL-6. This suggests that sgp130-based therapies may not be as impactful unless used at high and frequent doses. The model under discussion aimed at simulating its potential therapeutic use in conditions like Crohn’s disease. + +Overall, sgp130 is important for modulating IL-6 trans-signaling, but in the specific system modeled, its impact is limited under normal conditions due to its already high concentration compared to IL-6." +mw810ff751_fa4e_4143_bd50_169b3e325e1e,sR_IL6_sgp130,sR_IL6_sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context from the document, 'sR_IL6_sgp130' seems to be a part of the IL-6 signaling pathway and is likely a reference to a complex involving soluble IL-6 receptor components. Here's a summary based on the information provided and general knowledge: + +- **Biological Function:** The complex is involved in modulating IL-6 signaling, particularly influencing the trans-signaling mechanism. Soluble gp130 (sgp130) acts as a natural inhibitor of IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing it from associating with membrane-bound gp130, which is necessary for signal transduction. + +- **Role in Pathways:** It is a critical modulator in the IL-6 signaling pathway. Normally, IL-6 binds to the soluble IL-6 receptor (sIL-6R), and this complex can further engage with gp130 on cell surfaces to propagate downstream signaling events. The sgp130 serves as a sink for these IL-6/sIL-6R complexes, limiting their ability to bind to cellular gp130 and hence reducing downstream signaling such as STAT3 activation. + +- **Interactions with Other Molecules:** The complex interacts primarily with IL-6 and its soluble receptor (sIL-6R). It prevents these molecules from engaging with cell-surface gp130, thus acting as a competitive inhibitor in the pathway. + +- **Importance in the Biological System:** In the context of the system being modeled, sgp130 is crucial as it regulates the balance of IL-6 signaling. Its high baseline concentration relative to IL-6 suggests it plays a stabilization role in keeping the system responsive only to significant changes in IL-6 levels. However, its effectiveness as a therapeutic agent, such as in Crohn’s disease, may require high and frequent dosing due to its large baseline presence and minimal effect on system dynamics under normal conditions. + +No direct information about 'sR_IL6_sgp130' as a separate distinct entity is found in the context, suggesting it might be inferred from understanding sgp130's complex with IL-6 and sIL-6R within the described signaling and therapeutic contexts." +mw114aa90f_5f5b_4fe8_9406_361c8489b6a1,CRP,CRP,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The term 'CRP' within the context provided refers to C-reactive protein, rather than a distinct biological species. C-reactive protein is a well-known biomarker present in the bloodstream, often used to assess inflammation within the body. Here's a summary of relevant background information about CRP based on the context and general biological understanding: + +- **Biological Function**: C-reactive protein is an acute-phase protein produced by the liver in response to inflammation. Its primary role is to bind to the surface of dead or dying cells (and some types of bacteria) to activate the complement system, thereby promoting phagocytosis by macrophages. This function is part of the body's innate immune response, aiding in clearing pathogens and dead cells from the bloodstream. + +- **Role in Pathways**: CRP is part of the body's acute-phase response to inflammation. Its levels in the blood increase rapidly in response to inflammatory cytokines, such as interleukin-6 (IL-6). This makes CRP an integral component in pathways related to the immune system's response to infection, injury, or chronic inflammatory diseases. + +- **Interactions with Other Molecules**: CRP interacts with the complement system components, particularly C1q, to initiate the complement cascade, a series of reactions that help eliminate pathogens. It also interacts with receptors on the surfaces of immune cells, such as Fcγ receptors, facilitating opsonization and phagocytosis. The document mentions interactions with IL-6 and its receptor IL-6Rα, as CRP production is highly influenced by IL-6 signaling. + +- **Importance in Biological Systems**: In the context of the model described, CRP is used as a biomarker to assess inflammation levels in patients, particularly those with conditions such as Crohn's disease. The model measures CRP levels to validate its predictions regarding drug effects on inflammatory pathways, highlighting its utility in monitoring disease activity and treatment efficacy. + +Overall, CRP is a crucial component in biological models focused on inflammatory diseases due to its rapid and measurable response to changes in underlying inflammation." +mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc,sR,sR,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context, the species named 'sR' (ID: mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc) is likely related to the IL-6 signaling pathway. However, specific details about 'sR' are not provided directly in the context. Given that 'sR' is mentioned alongside IL-6, sIL-6R, and sgp130, it could be inferred that 'sR' is a component or modifier in the interleukin-6 (IL-6) signaling pathway. + +### Inferred Background Information + +**Biological Function**: +- It is probable that 'sR' is related to IL-6 signaling, potentially as a soluble receptor or co-receptor. Soluble receptors often exist as naturally occurring antagonists or helpers of cytokine signaling, modulating the pathway's activity. + +**Role in Pathways**: +- 'sR' might be involved in modulating the availability or activity of IL-6, similar to how sgp130 and sIL-6R work. sIL-6R is known to allow cells that do not possess membrane-bound IL-6R to respond to IL-6 through a process known as trans-signaling. + +**Interactions with Other Molecules**: +- It may interact with IL-6 or IL-6 receptor complexes. This interaction is crucial in the modulation of the pathway, likely affecting the downstream signaling events such as the activation of STAT3 (Signal Transducer and Activator of Transcription 3). + +**Importance in the Biological System**: +- Given its potential role in cytokine signaling, 'sR' would be important in regulating inflammatory responses, immune system signaling, and possibly in the pathophysiology of diseases where IL-6 is a key player, such as autoimmune diseases. + +### Contextual Consideration +- The provided context includes a discussion on sensitivity analysis and the role of sgp130 with IL-6, which highlights the intricate balance within the cytokine signaling pathways. Though 'sR' is not explicitly expanded upon, understanding the dynamics of similar molecules like sIL-6R and sgp130 offers insights into its potential biological significance. + +This inferred information aligns with typical roles of soluble cytokine receptors in biological systems. However, the exact nature and function of 'sR' would require further specific details or experimental data." +mw03db56ac_8dc6_4931_ae82_fef706d2ee3d,sR_IL6,sR_IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species labeled 'sR_IL6' in the context provided appears to refer to a soluble receptor for interleukin-6 (IL-6), often denoted as sIL-6R. Soluble IL-6 receptors play a crucial role in IL-6 trans-signaling pathways, which differ from classical signaling by involving the soluble receptor form (sIL-6R) rather than the membrane-bound IL-6 receptor (IL-6R). + +### Biological Function: +- **Soluble IL-6 Receptor (sIL-6R):** Its primary function is to bind to the cytokine IL-6, forming a complex that can activate cells that do not have membrane-bound IL-6 receptors. This process is known as ""trans-signaling"" and allows for a wider range of cells to respond to IL-6, expanding its biological effects. + +### Role in Pathways: +- **Trans-signaling Pathway:** In trans-signaling, the IL-6/sIL-6R complex associates with the membrane protein gp130, facilitating intracellular signaling cascades such as the JAK/STAT pathway. This activation leads to gene transcription and biological responses in target cells. +- **Classical Signaling Pathway:** sIL-6R is involved in sequestering IL-6 in the presence of the regulatory protein sgp130, modulating the signaling capacity by preventing excessive inflammatory signaling. + +### Interactions with Other Molecules: +- **IL-6:** The soluble receptor interacts with IL-6 to initiate trans-signaling. +- **gp130:** Binds the IL-6/sIL-6R complex, essential for downstream signal transduction. +- **sgp130:** Acts as a natural inhibitor by sequestering IL-6/sIL-6R complexes, dampening potential overactivation of IL-6 signaling. + +### Importance in the Biological System: +In the context of Crohn's disease and immune regulation, the IL-6/sIL-6R complex plays a critical role. Modulating this pathway can influence disease progression and therapeutic outcomes. Targeting the IL-6/sIL-6R complex could offer promising treatments by adjusting the immune response and inflammation characteristic of the condition. + +The context suggests that sIL-6R could be involved in a model for chronic inflammatory conditions, highlighting its significance in promoting or inhibiting inflammation through different signaling pathways. By understanding its interactions and functions, potential strategies can be developed for therapeutic interventions, such as using antibodies to modify its activity." +mwf345ed7a_0622_403c_b816_c8749a2c9ded,Ab,Ab,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided documents, there isn't direct and specific information regarding the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded) in the given context. However, based on general knowledge and context clues, 'Ab' likely refers to an antibody, given the reference to serum Ab concentrations and interaction with IL-6 and sIL-6Rα complexes. + +1. **Biological Function**: Antibodies (Ab) are proteins produced by the immune system that recognize and bind to specific antigens, such as pathogens (viruses, bacteria) or other target molecules. Their primary function is to neutralize these antigens and facilitate their destruction by other immune cells. + +2. **Role in Pathways**: In the context provided, 'Ab' is involved in targeting the IL-6 and IL-6Rα pathways. This is indicative of its role in modulating inflammatory responses, likely through the inhibition of the IL-6 signaling pathway. + +3. **Interactions with Other Molecules**: The document mentions the anti-IL-6 Ab dose response and its effects on serum CRP suppression. The interaction specifically involves the binding of the antibody to IL-6 and the IL-6/sIL-6Rα complex, which suggests its use in blocking or reducing the inflammatory signaling mediated by these molecules. + +4. **Importance in the Biological System**: The blocking or modulation of IL-6 signaling by antibodies plays a significant role in managing inflammatory diseases. The context implies that targeting IL-6 and its receptor complexes can be part of a therapeutic strategy for conditions characterized by excessive inflammation, such as inflammatory bowel diseases. + +Given these points, 'Ab' in this context seems to be associated with therapeutic antibodies used to manage inflammation by interfering with specific cytokine pathways, particularly involving IL-6. This type of intervention is crucial in diseases where cytokine signaling contributes to the pathology." +mw1da111f2_a036_4392_8512_015005bdcbb7,Ab_sR,Ab_sR,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The specific species 'Ab_sR' (ID: mw1da111f2_a036_4392_8512_015005bdcbb7) located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e does not seem to be explicitly mentioned in the provided context. However, based on the context and general knowledge, we can infer some relevant background information about similar biological components that usually appear in such contexts. + +The context mentions components such as sIL-6R, IL-6, and their interactions, which are indicative of a role in inflammatory response pathways. sIL-6R is a soluble form of the IL-6 receptor, and it typically participates in what's known as IL-6 trans-signaling. In this process, instead of the membrane-bound receptor, IL-6 binds to sIL-6R to form a complex that can interact with the gp130 protein, initiating signaling cascades even in cells that do not express the full receptor. This mechanism is important in regulating immune responses, inflammation, and possibly chronic inflammatory diseases by influencing the production of acute-phase proteins like C-reactive protein (CRP). + +Given this understanding, 'Ab_sR' could potentially refer to an antibody or an interaction factor related to the soluble receptor pathways, possibly playing a regulatory or inhibitory role in these pathways through binding interactions. Its importance might then be deduced from its capability to modulate these signaling pathways, with potential therapeutic implications for diseases driven by excessive IL-6 signaling. + +If Ab_sR is an antibody, it could play a role similar to antibodies against IL-6 or IL-6Rα, aiming to disrupt or modify these signaling pathways, potentially reducing inflammatory responses as a therapeutic strategy. Such antibodies are being explored in contexts of autoimmune diseases, cancers, and inflammatory disorders. + +Note: This inference is made based on the context provided and common biological functions of related components. Further specific information would be required for more accurate detailing of Ab_sR's role." +mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac,Ab_sR_IL6,Ab_sR_IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The context provided does not directly specify information about a species named 'Ab_sR_IL6'. However, based on general knowledge and the context given, we can make some inferences and provide related information: + +1. **Biological Function**: Given the naming convention used ('Ab_sR_IL6'), it is likely that this refers to an antibody (Ab) targeting a soluble receptor (sR) for interleukin-6 (IL-6), possibly inhibiting its action. IL-6 is a cytokine involved in inflammatory and immune responses. + +2. **Role in Pathways**: IL-6 typically signals through its receptor complex, including IL-6R and gp130, to activate downstream signaling pathways like JAK/STAT, leading to the activation of transcription factors such as STAT3. This cascade leads to the expression of various genes involved in inflammation and immune regulation. + +3. **Interactions with Other Molecules**: Based on the context, the antibody could be interacting with the IL-6/sIL-6R complex to modulate its effects. The text describes interactions involving sIL-6R and IL-6, potentially including competition or inhibition by antibodies that alter the signaling outcomes and inflammatory responses. + +4. **Importance in the Biological System Being Modeled**: In the context of the model described, inhibiting the IL-6/sIL-6R interaction is a focus, likely due to its role in conditions like Crohn's Disease or rheumatoid arthritis. Modifying this pathway's activity through an antibody such as 'Ab_sR_IL6' might be of therapeutic significance, potentially helping to suppress excessive inflammatory responses, as suggested by the interest in CRP (C-reactive protein) suppression and dose-response relationships. + +In summary, 'Ab_sR_IL6' is likely conceptualized as an antibody targeting the soluble IL-6 receptor to interfere with IL-6 mediated signaling pathways, which are pivotal in certain inflammatory diseases. While specific details are not provided in the context, this inference aligns with common therapeutic strategies involving cytokine signaling modulation." +CRP_Suppression___,CRP Suppression (%),CRP Suppression (%),mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the context provided, ""CRP Suppression (%)"" refers to the measurement of the reduction in serum C-reactive protein (CRP) levels. CRP is a biological marker of inflammation, and its levels can be indicative of inflammatory responses in the body. Understanding the suppression of CRP levels has the following implications: + +1. **Biological Function**: CRP is an acute phase protein, produced by the liver in response to inflammation. It plays a role in the body's immune response, indicating tissue damage or inflammation. + +2. **Role in Pathways**: CRP is involved in the inflammatory pathway. Suppressing CRP levels typically suggests an underlying modulation of the inflammatory response, often facilitated through interventions like antibodies targeting specific inflammatory cytokines or receptors, such as IL-6 or IL-6Rα in this context. + +3. **Interactions with Other Molecules**: The context implies interactions with Interleukin-6 (IL-6) and its receptor (IL-6Rα). Treatments with anti–IL-6 or anti–IL-6Rα antibodies reduce CRP levels, thereby modulating inflammation, as indicated by the provided data on drug dose and CRP suppression. + +4. **Importance in the Biological System**: Suppression of serum CRP is an important indicator of the efficacy of drugs, like anti-IL-6 or anti-IL-6Rα antibodies, in reducing inflammatory responses. This makes CRP suppression a critical measure for evaluating the outcome of therapeutic interventions aimed at inflammatory diseases. + +While the context does not directly describe CRP Suppression (%) as a biological species, it is a measure of the effectiveness of treatments targeting inflammatory pathways. Interactions that lead to its suppression are essential for understanding therapeutic impacts on inflammation-related conditions." +CRP____of_baseline,CRP (% of baseline),CRP (% of baseline),mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The term ""CRP (% of baseline)"" is referring to C-reactive protein (CRP) levels measured as a percentage of a baseline value. In the context provided, it appears to be a metric used in the modeling and analysis of clinical trial data related to anti–IL-6Rα antibody treatments, specifically tocilizumab, which is an anti-inflammatory medication. Here's a summary based on the context and general knowledge about CRP: + +1. **Biological Function:** + - CRP is a protein produced by the liver in response to inflammation. It is part of the acute phase response to inflammation and is a biomarker commonly used to assess inflammation and tissue injury. + +2. **Role in Pathways:** + - CRP is a key player in the acute inflammatory response and is involved in pathways that react to injury, infection, and inflammation. It interacts with the immune system to facilitate the clearance of necrotic and apoptotic cells and bacteria. + +3. **Interactions with Other Molecules:** + - CRP levels are influenced by the presence of pro-inflammatory cytokines, particularly interleukin-6 (IL-6). This context highlights the interaction between CRP levels and anti–IL-6Rα antibodies, which inhibit IL-6 signaling and therefore can suppress CRP production as part of their therapeutic action. + +4. **Importance in the Biological System Being Modeled:** + - In the given context, CRP (% of baseline) serves as an important biomarker for evaluating the efficacy of tocilizumab treatment in suppressing inflammation. The model uses CRP levels to compare and validate simulation results against clinical trial data, indicating its critical role in assessing treatment impacts. + +No specific unique details beyond this general framework are detailed in the context, but from a systems biology perspective, CRP measurement is significant for understanding inflammatory processes and the body's response to therapeutic interventions." +mw80848184_e2dd_47ce_86d7_7a21479342bd,gp130,gp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species named 'gp130' refers to a protein that plays a significant role in the signaling pathway involving interleukin-6 (IL-6) and its receptor. + +### Biological Function: +- **gp130 is a Signal Transducer**: It is primarily a signal-transducing component of the IL-6 receptor complex. It does not bind IL-6 by itself but acts as a signal transducer when associated with IL-6 and IL-6 receptor (IL-6R). + +### Role in Pathways: +- **Interaction with IL-6/IL-6R**: gp130 is crucial in the formation of the signaling complex with IL-6 and its soluble receptor sIL-6R. This complex is central to IL-6 signaling pathways. +- **Inhibition of IL-6 Trans-Signaling**: A fusion protein known as sgp130Fc, which combines the extracellular portion of gp130 with an Fc region, has been shown to inhibit IL-6 trans-signaling, demonstrating gp130’s role in regulatory mechanisms. + +### Interactions with Other Molecules: +- **Complex Formation**: It forms a complex with IL-6 and IL-6R, contributing to signal transduction. +- **Natural Inhibitor**: Soluble gp130 (sgp130) serves as a natural inhibitor of the IL-6/sIL-6R signaling pathway, preventing excessive signal transduction. + +### Importance in the Biological System: +- **Regulatory Role**: The high baseline level of soluble gp130 (sgp130) in the system acts as a buffering agent against changes in the levels of IL-6/sIL-6R complex, highlighting its regulatory importance. +- **Therapeutic Potential**: Therapeutic approaches using sgp130 to target IL-6 signaling pathways, such as in the treatment of Crohn’s disease, underscore its clinical significance. + +Given these roles, gp130 is a critical component in the IL-6 signaling pathway and has potential therapeutic implications due to its regulatory capacities in controlling inflammatory responses." +mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a,R_IL6_gp130,R_IL6_gp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species named 'R_IL6_gp130', based on its naming and the context provided, likely refers to a complex or interaction involving the cytokine interleukin-6 (IL-6) and the signal transducer glycoprotein 130 (gp130). While the specific document does not provide detailed information about R_IL6_gp130, general knowledge about the IL-6/gp130 interaction helps us understand its potential biological significance. + +### Biological Function: +- **IL-6:** It is a cytokine involved in the regulation of immune responses, inflammation, and hematopoiesis. It plays a crucial role in acute phase responses and is produced at sites of inflammation. +- **gp130:** It serves as a signal transducer in the cytokine receptor complex, particularly for the IL-6 family of cytokines. It is involved in several cellular processes, including cell growth and differentiation. + +### Role in Pathways: +- The IL-6/gp130 interaction is central to both classical and trans-signaling pathways. In classical signaling, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), which then associates with gp130 to initiate downstream signaling. +- In trans-signaling, IL-6 binds to a soluble form of the IL-6 receptor (sIL-6R), and this complex can then associate with gp130 on the target cell surface, allowing cells that do not express membrane-bound IL-6R to respond to IL-6. + +### Interactions with Other Molecules: +- gp130 is a common subunit shared by several cytokine receptors in the IL-6 family, meaning it participates in a variety of signaling complexes. +- The soluble form of gp130 (sgp130) can act as a natural inhibitor by binding to IL-6/sIL-6R complexes and preventing them from interacting with membrane-bound gp130. + +### Importance in the Biological System Being Modeled: +- Given the context of inflammatory diseases such as Crohn’s disease, the IL-6/gp130 axis is likely a critical component in the inflammatory response modulation. +- The application of sgp130, or its fusion forms like sgp130Fc, demonstrates the pathway's therapeutic significance as a target for damping excessive IL-6-mediated signaling in inflammatory diseases. + +In summary, R_IL6_gp130 refers to a key interaction in the IL-6 signaling pathway, emphasizing its role in inflammatory responses and its potential as a therapeutic target in autoimmune diseases like Crohn's." +mw4638f126_8cb8_4021_ab41_6ae195743ba0,"sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context and general knowledge, here is the background information on the species 'sR_IL6' with the identifier 'mw4638f126_8cb8_4021_ab41_6ae195743ba0', situated within 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e': + +1. **Biological Function**: 'sR_IL6' likely refers to the soluble receptor for Interleukin-6 (sIL-6R). Soluble receptors such as sIL-6R can bind to the cytokine IL-6, acting as a co-receptor that allows IL-6 to engage in signaling pathways even in cells that do not express the membrane-bound IL-6 receptor. + +2. **Role in Pathways**: In the immune system, IL-6 can signal through two main pathways: + - **Classical signaling**: IL-6 binds to membrane-bound IL-6R and recruits the gp130 protein to initiate downstream signaling. + - **Trans-signaling**: sIL-6R, in complex with IL-6, engages gp130 on cells that do not have the IL-6 receptor, thus expanding the range of cells that can respond to IL-6. This is particularly relevant in inflammatory responses and is studied in contexts such as Crohn's disease. + +3. **Interactions with Other Molecules**: + - sIL-6R forms a complex with IL-6 which can then bind to gp130, leading to activation of downstream signaling pathways such as the JAK/STAT pathway. + - sIL-6R can be sequestered by sgp130, a soluble form of gp130, which can regulate the availability of the IL-6/sIL-6R complex for signaling. + - C-reactive protein (CRP) is involved in the production of sIL-6R through a process known as CRP-mediated shedding. + +4. **Importance in the Biological System**: + - sIL-6R plays a crucial role in mediating IL-6 trans-signaling, particularly in contexts like chronic inflammation and autoimmune diseases such as Crohn's disease. + - The presence of sIL-6R enables IL-6 to exert its effects even in cells lacking direct IL-6 receptors, thereby widening its scope of action within the immune regulatory processes. + - Understanding the dynamics of sIL-6R in combination with IL-6 is important for therapeutic considerations, as targeting these complexes can influence pharmacological outcomes in disease states. + +Thus, sR_IL6 (inferred as sIL-6R) is integral to the IL-6 signaling pathways, facilitating broad immunological responses through its role in trans-signaling and interaction with IL-6 and other molecular regulators like sgp130." +mw10315fa3_6f13_4618_bda8_a8694bd3c374,R,R,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Given the context provided, the information about the species named 'R' (ID: mw10315fa3_6f13_4618_bda8_a8694bd3c374) is not directly mentioned in the documents. However, we can make inferences based on the information about related molecules and pathways described in the context, particularly those involving IL-6 (interleukin-6) and its receptor. + +### Inferred Background Information about 'R': + +1. **Biological Function**: + - Since the context discusses IL-6 and its receptors (sIL-6R and IL-6Rα), 'R' could potentially be related to components in the IL-6 signaling pathway. IL-6 is a cytokine involved in inflammation and immune response regulation. + +2. **Role in Pathways**: + - IL-6 interacts with both membrane-bound and soluble forms of its receptor (IL-6R) to initiate downstream signaling cascades, such as the JAK/STAT pathway, which leads to the activation of transcription factors like STAT3 (signal transducer and activator of transcription 3). + - The pathway is involved in the transcription of various genes, including those coding for acute-phase proteins like CRP (C-reactive protein), indicating a role in inflammatory processes and liver function. + +3. **Interactions with Other Molecules**: + - IL-6, in combination with its receptor, can activate a signaling complex that involves the JAK proteins and STAT3, influencing gene expression. Soluble forms of the receptor, such as sIL-6R, play a role in trans-signaling, which can modulate responses in cells that do not express the membrane-bound receptor. + +4. **Importance in the Biological System**: + - Given that IL-6 signaling impacts acute-phase response and immune regulation, molecules within this pathway, including 'R' if it is part of this system, are crucial for modulating inflammatory responses. They may be targeted in therapeutic contexts, such as with anti–IL-6 or anti–IL-6Rα therapies, which are indicated in the documents as treatments influencing biomarkers like CRP. + +In conclusion, without specific data directly linked to 'R', it can be inferred that 'R' is potentially part of the IL-6 pathway components, involved in immune and inflammatory responses, and plays a significant role in cellular signaling and communication within this biological system." +mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1,"IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, the species referred to as 'IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is likely Interleukin-6 (IL-6), a cytokine involved in various biological processes. Here is a summary of relevant background information about IL-6: + +1. **Biological Function:** + - IL-6 is a cytokine that plays a crucial role in immune regulation. It is involved in the inflammatory response and is essential for the body's defense against infections and injuries. + +2. **Role in Pathways:** + - IL-6 signaling can occur through two main pathways: + - **Classical Pathway:** This involves the membrane-bound IL-6 receptor (IL-6Rα) where IL-6 binds to IL-6Rα, forming a complex that recruits a membrane-bound gp130 coreceptor, triggering downstream signaling cascades. + - **Trans-signaling Pathway:** This involves the soluble IL-6 receptor (sIL-6Rα). The IL-6/sIL-6Rα complex can associate with gp130 to initiate signaling in cells that do not express the membrane-bound IL-6Rα. This pathway is particularly important in inflammatory diseases. + +3. **Interactions with Other Molecules:** + - IL-6 interacts with IL-6Rα and gp130 to form a receptor complex that activates intracellular signaling pathways. + - It leads to the phosphorylation of Janus kinase (Jak) family proteins and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3), which are critical for transmitting the signal inside the cell. + +4. **Importance in the Biological System Being Modeled:** + - In the context of Crohn's disease, IL-6 contributes to enhanced T-cell survival and resistance to apoptosis in the lamina propria, along with elevated chemokine secretion. This makes it a significant player in the disease's pathology. + - The study of IL-6 and its pathways is crucial in understanding its role in diseases such as Crohn's disease and rheumatoid arthritis, and in developing therapeutic interventions targeting IL-6 signaling. + +Overall, IL-6 is an important cytokine with significant roles in immune response and inflammation, making it a key target for research in immune-mediated diseases." +mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83,R_IL6,R_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, there is no specific mention of a species named 'R_IL6'. However, based on the context and related molecules mentioned, it is possible to infer some insights into what 'R_IL6' might relate to. + +### Biological Function: +- **IL-6:** IL-6 (Interleukin-6) is a cytokine involved in immune response, inflammation, and hematopoiesis. It plays a significant role in the body's defense mechanisms and is implicated in various diseases when dysregulated. + +### Role in Pathways: +- **IL-6 Signaling Pathway:** This pathway involves the binding of IL-6 to its receptor, IL-6R, and generally leads to the activation of JAK/STAT signaling pathways. This signaling can induce transcription and various immune responses. + +### Interactions with Other Molecules: +- **IL-6R and sIL-6R (soluble IL-6 receptor):** The IL-6 signaling requires the complex formation of IL-6 with its receptor IL-6R, including its soluble form sIL-6R. This complex can further bind to another molecule, gp130 (glycoprotein 130), which is necessary for signal transduction. +- **STAT3:** The context mentions pSTAT3 signaling, indicating that IL-6 signaling involves phosphorylation of STAT3, a transcription factor that mediates various gene expressions in response to IL-6. + +### Importance in the Biological System Being Modeled: +- **Regulation and Modeling:** IL-6 is involved in the regulation of immune processes, and its signaling is crucial in understanding conditions like Crohn's disease or rheumatoid arthritis. The context mentions modeling efforts and pharmacokinetic analyses suggesting a focus on IL-6 and its receptor interactions. +- **Treatment Implications:** The modeling discussed, such as the dose-response characteristics, indicates IL-6's importance in therapeutic frameworks, potentially focusing on disorders with immune dysregulation. + +### Potential Inference for 'R_IL6': +- While there is no direct mention of 'R_IL6', it could potentially refer to a variant, receptor, or complex of IL-6 involved in signaling pathways. It might be modeled similarly in studies related to immune regulation or therapeutic targeting. Given the context, it is likely associated with IL-6's complex pathways and interactions within the immune system. + +In summary, 'R_IL6' could be a component related to IL-6 signaling, likely significant in immune system modeling and therapeutic interventions." +mw0eb6c959_d408_45a0_a450_928b8c5876bb,Ractive,Ractive,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided does not include specific information about a species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). However, I can provide inferential information based on the general context described, which involves IL-6 signaling and therapeutic interventions in conditions like rheumatoid arthritis and Crohn’s disease. + +1. **Biological Function:** + - Although 'Ractive' is not directly mentioned, within the context of an immune regulation framework, it could be hypothesized that 'Ractive' might represent a molecule involved in the immune response or signal transduction, perhaps similar to interleukins or receptors. + +2. **Role in Pathways:** + - Considering the IL-6 signaling pathway is a focal point of the study, 'Ractive' might play a role similar to elements of the IL-6 signaling cascade. This could involve participation in cytokine signaling or acting as a receptor or receptor complex, similar to IL-6 or its soluble receptor counterparts. + +3. **Interactions with Other Molecules:** + - 'Ractive' might engage in interactions akin to the IL-6 and its soluble receptor interactions. Such molecules often form complexes that could be potential targets for therapeutic antibodies or other modulators, a common approach in autoimmune conditions like those discussed. + +4. **Importance in the Biological System:** + - If 'Ractive' partakes in a pathway analogous to IL-6 signaling, it could be crucial in mediating inflammatory responses, playing a part in disease progression or resolution, and thus presenting itself as a possible target for therapeutic intervention. + +Without specific information on 'Ractive' from the text, these interpretations are speculative and should be considered within the broader context of known signaling pathways and therapeutic targets discussed in the study." +mw42054cd7_17af_46da_970c_7f99151906ad,STAT3,STAT3,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context and general knowledge: + +### Biological Function of STAT3 +STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor activated by phosphorylation. It is a key player in transmitting signals from various cytokines and growth factors to the cell nucleus, where it modifies gene expression. STAT3 is critical for regulating numerous biological processes, including cell growth, apoptosis, and immune response. + +### Role in Pathways +STAT3 is involved in the JAK-STAT signaling pathway. Upon activation, typically by cytokines such as IL-6, STAT3 is phosphorylated by associated Janus kinases (JAKs), dimerizes, and translocates to the nucleus. In this context, STAT3 appears integral to the IL-6 signaling pathway, which is involved in various cellular responses, including inflammation, immune function, and acute-phase reactions. + +### Interactions with Other Molecules +Within the IL-6 signaling pathway, STAT3 interacts with molecules such as the IL-6 receptor (IL-6R), gp130, and soluble forms of these receptors (sIL-6R and sgp130). The phosphorylation of STAT3 (pSTAT3) indicates its activation and subsequent transcriptional regulation of target genes. + +### Importance in Biological Systems +STAT3 plays a significant role in mediating the effects of cytokines like IL-6, which are crucial in immune responses and inflammation. The context mentions disease models such as Crohn's disease, where increased activation of STAT3 (pSTAT3) in tissues is noted, highlighting its potential role in the disease's inflammatory processes. This suggests that STAT3's regulation is pivotal in understanding and developing therapeutic approaches for immune and inflammatory disorders. + +In summary, STAT3 is a central molecule in cytokine signaling pathways that influence immune function and inflammation, making it a critical target for studying diseases characterized by dysregulated immune responses, such as Crohn's disease." +mw39c2e431_fdc3_4964_be29_6ca856620b1b,pSTAT3,pSTAT3,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided mainly revolves around the IL-6 signaling pathway and its components, such as IL-6Rα, gp130, sIL-6Rα, sgp130, and CRP, with sporadic mentions of STAT3 and pSTAT3. Here’s a summary focused on pSTAT3 based on the document and broader biological knowledge: + +### pSTAT3 Biological Function +- **pSTAT3** refers to the phosphorylated form of STAT3 (Signal Transducer and Activator of Transcription 3). +- STAT3 is a transcription factor activated in response to cytokines like IL-6. +- When phosphorylated, STAT3 dimerizes and translocates to the nucleus to regulate the expression of target genes. + +### Role in Pathways +- **IL-6 Signaling**: pSTAT3 is a critical component of the IL-6 signaling pathway. The binding of IL-6 to its receptor leads to the activation of the JAK kinases, which in turn phosphorylate STAT3. +- **Gene Expression**: pSTAT3 influences the transcription of various genes involved in immune responses, cell survival, and proliferation. + +### Interactions with Other Molecules +- **IL-6 and sIL-6Rα**: The context describes the significance of trans-signaling mediated by IL-6 and its soluble receptor forms, which lead to STAT3 phosphorylation. +- **gp130**: This coreceptor is crucial for the activation of STAT3. It binds the IL-6/sIL-6R complex leading to STAT3 phosphorylation. +- **CRP and other gene products**: The activation of STAT3 can influence the expression of C-reactive protein and other acute-phase proteins. + +### Importance in the Biological System +- **Pathological Conditions**: The document mentions increased pSTAT3 levels in colon biopsies in the context of Crohn’s disease, suggesting its role in inflammatory bowel diseases. +- **Biological Significance**: Being a part of the IL-6 signaling pathway, pSTAT3 is important in mediating immune responses and might have implications in various diseases due to dysregulated cytokine signaling. + +In summary, pSTAT3 is a pivotal signaling molecule involved in transcriptional regulation, primarily within the IL-6-mediated pathway. Its phosphorylation status determines its activity, which can impact various biological processes and contributes to disease states such as inflammatory bowel disease." +mwd5313618_89eb_4c8c_bc82_66f10f966349,"CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",CRP,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species referred to as ""CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)"" in the provided context likely represents C-reactive protein (CRP), based on the common abbreviation for C-reactive protein. Here is a summary of the relevant background information regarding CRP: + +1. **Biological Function:** + - CRP is an acute-phase protein produced by the liver in response to inflammation. Its primary function is to bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system via C1q. + +2. **Role in Pathways:** + - CRP is often used as a clinical biomarker for inflammation. It plays a significant role in the pathway of immune response, particularly in recognizing and promoting the clearance of pathogens and damaged cells, thereby serving as a marker of inflammation and immune system activation. + - In the context of the simulation model discussed, changes in CRP levels can indicate the effectiveness of drug treatments targeting the IL-6 signaling pathway, as CRP levels are a downstream effect of cytokine signaling, particularly IL-6. + +3. **Interactions with Other Molecules:** + - CRP interacts with various components of the immune system such as the complement system. It works closely with interleukin-6 (IL-6), as IL-6 is a major inducer of CRP synthesis in the liver. + - The context mentions interactions with drugs such as anti-IL-6Rα antibodies, which suggests that CRP levels are used to measure the impact of these treatments on inflammation levels in diseases like Crohn's disease. + +4. **Importance in the Biological System Being Modeled:** + - Within the modeled system (as described in the context), CRP serves as a critical marker for inflammation, allowing researchers to predict the impact of various treatment strategies on inflammatory diseases like Crohn's disease. + - The model’s ability to predict changes in CRP levels helps in studying the effects of perturbations through different therapeutic approaches aimed at inhibiting the IL-6 signaling pathway. + +Overall, CRP is an important indicator of inflammation and is crucial in the validation and assessment of disease models involving inflammatory processes, such as those involving IL-6 signaling." +mw2e464cf3_a09c_4b7c_9f3c_06720016a48e,"sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, specific information about the species 'sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned. However, inferring from the general context of the documents, which involve molecular interactions and pathways related to the IL-6 signaling system, the following insights can be suggested: + +1. **Biological Function**: + - The 'sR' component is likely a part of the IL-6 signaling pathway. In similar contexts, 'sR' often denotes soluble receptors. Soluble receptors can modulate the activity of their respective cytokines or hormones by binding to them and altering their bioavailability or impacting downstream signaling pathways. + +2. **Role in Pathways**: + - Considering the IL-6 pathway is mentioned, the 'sR' species might function in the classical signaling or trans-signaling pathways of IL-6. In these pathways, soluble receptors either enhance or inhibit signal transduction, impacting gene expression mediated by factors like STAT3. + +3. **Interactions with Other Molecules**: + - The context suggests interaction with the IL-6 cytokine, as soluble IL-6 receptors (e.g., sIL-6R) bind IL-6, forming a complex (IL-6:sR) that may interact with other receptor components, such as gp130, to elicit a cellular response. These interactions are crucial for regulating inflammatory responses and immune function. + +4. **Importance in the Biological System Being Modeled**: + - Soluble receptors are significant in maintaining homeostasis and regulating the intensity of cytokine signaling. The modeling aspect suggests that understanding the dynamic balance of these components (like sgp130, mentioned in the document) is crucial for accurately predicting system behavior under various conditions and treatments, especially targeting IL-6 or its receptors. + +In summary, 'sR' in this context is likely a soluble receptor involved in the IL-6 signaling pathway, influencing immune responses by modulating cytokine availability and activity." +mw36ea78c1_ed71_4def_96d3_857a442d7195,CRPExtracellular,CRPExtracellular,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species named 'CRPExtracellular' likely refers to the extracellular form of C-reactive protein (CRP), a well-known biomarker and acute-phase protein in various biological systems, particularly in the context of inflammation. + +### Biological Function +C-reactive protein (CRP) is produced by the liver in response to inflammation. It is an acute-phase protein that plays a critical role in the host's defense mechanism. CRP is part of the innate immune system as it binds to the surface of dead or dying cells and certain bacteria to activate the complement system, promoting phagocytosis by macrophages. + +### Role in Pathways +In the context of the provided documents, CRP is linked to the IL-6 signaling pathway. IL-6 is a cytokine that stimulates the production of CRP in the liver. The IL-6 mediated pathway contributes to inflammatory responses, and CRP serves as a downstream marker for inflammation. The model mentioned explores strategies to treat Crohn's disease by inhibiting IL-6 signaling, which suggests a modulation of CRP levels. + +### Interactions with Other Molecules +CRP interacts with various molecules and systems in the body: +- It binds to phosphocholine on the surface of dead cells and some types of bacteria. +- CRP activates the complement system, which enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells. +- CRP levels are used to assess the extent of inflammation in response to stimuli like IL-6, another cytokine involved in the body's inflammatory response. + +### Importance in the Biological System Being Modeled +In the biological model presented in the documents, CRP serves as a critical biomarker to evaluate the efficacy of therapeutic strategies targeting IL-6 signaling in inflammatory diseases like Crohn's disease. The documents emphasize the model's capacity to predict the response of CRP levels to different treatment strategies, validating the trained model against clinical trial data. Suppression of CRP is an indicator of effective inhibition of inflammation, showcasing the importance of CRP measurement in assessing the success of interventions aimed at controlling inflammatory pathways. + +In summary, CRPExtracellular represents the extracellular C-reactive protein operating as a biomarker for inflammation, influenced by IL-6 signaling pathways, and significant in evaluating treatment efficacy for diseases characterized by chronic inflammation." +mw147d30ec_478e_4090_b496_128a131d29eb,"sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sgp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species referred to as 'sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' appears to be a protein known as sgp130 located in a specific biological context (ID: mw147d30ec_478e_4090_b496_128a131d29eb). Here is a summary of the relevant background information: + +1. **Biological Function**: + sgp130 is a soluble form of gp130, which is a component of the IL-6 receptor complex. sgp130 acts by binding to the IL-6/sIL-6Rα complex, thereby inhibiting IL-6 trans-signaling. This function is crucial as IL-6 trans-signaling is associated with various inflammatory and autoimmune conditions. + +2. **Role in Pathways**: + sgp130 plays a role in the IL-6 signaling pathway by inhibiting the formation of active signaling complexes. This modulation of the pathway can potentially reduce inflammatory responses mediated through IL-6 trans-signaling. + +3. **Interactions with Other Molecules**: + sgp130 interacts specifically with the complex formed by IL-6 and its soluble receptor sIL-6Rα. By binding to this complex, sgp130 prevents the subsequent interaction with the membrane-bound gp130, effectively blocking signal transduction. + +4. **Importance in the Biological System Being Modeled**: + In the context of therapeutic applications, particularly for conditions such as Crohn's disease, sgp130 is evaluated for its potential use in inhibiting inflammatory signaling. Despite being present in large concentrations compared to IL-6, sensitivity analyses suggest that the therapeutic effectiveness of sgp130-based interventions may require very high doses due to its minimal impact on overall system dynamics at typical concentrations. This is because sgp130 naturally exists in excess relative to IL-6, limiting its impact when used in moderate amounts. + +5. **Relevance in Systems Biology Model**: + The systems biology model suggests that while sgp130 has a role, its overall impact on key output parameters (such as CRP levels) is limited unless used in substantial amounts. It highlights the need for potentially better therapeutic targets like IL-6 and sIL-6Rα, where alterations could more significantly affect system outputs. + +Overall, sgp130 serves a regulatory function in IL-6 mediated signaling, highlighting its role in inflammatory pathways but with suggested limitations for therapeutic application based on the systems biology model being considered." +mwab41493c_6349_45f1_a226_3030cfed0e06,"sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR_IL6_sgp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, the species 'sR_IL6_sgp130', identified by the ID mwab41493c_6349_45f1_a226_3030cfed0e06, appears to be related to a fusion protein that plays a role in inhibiting IL-6 trans-signaling pathways. This fusion protein, popularly referred to as sgp130Fc, combines the extracellular portion of glycoprotein 130 (gp130) with the Fc region of human IgG1. + +**Biological Function:** +sR_IL6_sgp130 acts to bind specifically to the IL-6/sIL-6Rα complex, which is pivotal in mediating IL-6 trans-signaling. By binding to this complex, it effectively prevents the signaling process that would typically activate downstream pathways, such as the phosphorylation of STAT3 (pSTAT3) and subsequent gene transcription. + +**Role in Pathways:** +Its primary role resides in the inhibition of IL-6 trans-signaling, which is critical in the context of inflammatory responses and diseases like Crohn’s disease. The simulations and models cited suggest that this species is involved in modifying the dose-response relationship of certain therapeutic interventions, leading to outcomes like CRP suppression. + +**Interactions with Other Molecules:** +sR_IL6_sgp130 interacts predominantly with the IL-6/sIL-6Rα complex. The sgp130 component has a high affinity for this complex, which is a major interaction through which it achieves its inhibitory functions. + +**Importance in the Biological System Being Modeled:** +In the system, while sR_IL6_sgp130 is present in high baseline levels and exerts limited effects on steady-state system dynamics due to its excess relative to free IL-6 concentrations, it remains a pivotal molecule for therapeutic applications. Its primary importance lies in its use as a potential therapeutic intervention, especially considered for conditions with elevated IL-6 trans-signaling, requiring very high and frequent doses to be effective due to its baseline levels. + +This summary indicates that sR_IL6_sgp130 is critical in the context of therapies aiming to modulate IL-6 signaling pathways, providing insights into the need for precise dosing strategies to achieve therapeutic benefits." +mwf405687b_7401_44ec_a0d6_4a2b35c13e8a,"Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab_sR,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, no specific information about the species named 'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' was found in the excerpts from the document. However, I can infer some potential characteristics and roles it might have based on general biological knowledge and the information typically associated with similar components. + +1. **Biological Function**: Generally, ""Ab"" in a biological context often refers to antibodies. If 'Ab_sR' is indeed an antibody or related to antibody activity, its function could be to bind to specific antigens, perhaps part of a signaling pathway or immune response mechanism. + +2. **Role in Pathways**: The context mentions IL-6 and its receptor interactions, which are part of immune signaling pathways. If 'Ab_sR' is interacting with such pathways, it could be modulating or inhibiting specific signals, particularly in inflammatory or immune responses. + +3. **Interactions with Other Molecules**: As the context heavily references IL-6, IL-6R, and associated signaling components like STAT3 and SOCS, it is plausible that 'Ab_sR' could interact with these molecules. It might bind to a receptor or signaling molecule to alter its activity. + +4. **Importance in the Biological System**: Assuming 'Ab_sR' is an antibody related to receptor activity, it could be crucial in modulating inflammatory responses or other cytokine-related pathways. In systems biology models, such antibodies are often used to simulate therapeutic interventions, inhibiting specific pathways to predict changes in disease states or therapeutic outcomes. + +Without explicit details from the document, these inferences remain general and speculative. Further details would be needed for precise characterization." +mw3667a5e1_02c9_44a0_acb4_b0431faa822d,"Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, there isn't directly available specific information about the species named 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, we can infer its role based on general knowledge and the content present in the documents. + +1. **Biological Function:** 'Ab' likely refers to an antibody, given the context of medical and pharmacological studies. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. + +2. **Role in Pathways:** Antibodies are a crucial part of the immune response, often engaging in pathways related to immune regulation and inflammatory responses. Specifically, within the context, it seems to be involved in pathways targeting IL-6 or IL-6Rα, which are significant in inflammatory processes and immune system signaling, especially in conditions like inflammatory bowel diseases and other inflammatory responses. + +3. **Interactions with Other Molecules:** Within the context, the antibodies interact with IL-6 and sIL-6Rα (soluble IL-6 receptor alpha). These interactions are essential as they form complexes that are targets for therapeutic interventions to suppress inflammatory markers like C-reactive protein (CRP). The effectiveness of such interventions can vary based on whether IL-6 and its receptor are targeted individually or together. + +4. **Importance in the Biological System:** Antibodies, like the one inferred (potentially anti-IL-6 or similar), are important in modulating the immune response and are used in therapeutic settings to treat diseases where cytokine activity (like that of IL-6) is dysregulated. They help reduce undesirable inflammation and are thus a critical part of managing inflammatory diseases. + +In summary, while specific details about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' are not provided, it is most likely a therapeutic antibody involved in pathways targeting IL-6 and its receptor, pivotal in controlling inflammation within biological systems." +mw772cbf20_3fc1_4800_ae59_77884f1ae333,Ab_R,Ab_R,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The document provided does not explicitly mention the species 'Ab_R' with the ID 'mw772cbf20_3fc1_4800_ae59_77884f1ae333.' Therefore, I will infer what 'Ab_R' might pertain to based on the general knowledge presented in the context and common biological components. + +1. **Biological Function:** + - Given that the context mentions anti-IL-6 and anti-IL-6Rα antibodies, it is plausible that 'Ab_R' could represent an antibody (Ab) related to these immune system components. + +2. **Role in Pathways:** + - Antibodies targeting the IL-6/IL-6Rα pathway are involved in modulating inflammatory responses. IL-6 is a cytokine involved in immune regulation, and its receptor, IL-6Rα, can exist in both a soluble and membrane-bound form, playing roles in signaling cascades that promote inflammation. + +3. **Interactions with Other Molecules:** + - If 'Ab_R' is, in fact, an antibody similar to anti-IL-6 or anti-IL-6Rα, it would likely bind to these targets to inhibit cytokine signaling, thereby reducing inflammation. It may interact with IL-6, IL-6Rα, or both. + +4. **Importance in the Biological System Being Modeled:** + - The context of the document suggests a focus on modeling pharmacokinetics and pharmacodynamics (PK/PD) of antibodies targeting IL-6/IL-6Rα pathways, often to evaluate potential therapeutic interventions for conditions involving chronic inflammation, such as autoimmune diseases or inflammatory diseases like Crohn’s disease (CD). + - Such antibodies can serve as therapeutic agents to suppress the inflammatory response by antagonizing the IL-6 pathway, therefore reducing downstream effects like C-reactive protein (CRP) levels, which is a marker of inflammation. + +Conclusively, while the document does not provide direct information on 'Ab_R,' it is likely aligned with therapeutic antibodies targeting cytokine signaling pathways to control inflammation within a modeled biological framework." +mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf,"Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab_sR_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned in the provided context. However, it is possible to infer details about this species based on the context and general knowledge about similar biological components, such as sIL-6R and IL-6. + +1. **Biological Function**: + - Since 'Ab_sR_IL6' likely refers to an antibody (Ab) targeting soluble IL-6 receptor (sIL-6R), its primary function would be to bind soluble IL-6R, potentially inhibiting its interaction with IL-6. + +2. **Role in Pathways**: + - In immune regulation pathways, particularly those involving interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R) can form complexes with IL-6 to mediate signaling even in cells that do not express membrane-bound IL-6R. By targeting sIL-6R, the antibody could disrupt these signaling cascades, serving as a potential therapeutic strategy in diseases characterized by excessive IL-6 signaling, such as rheumatoid arthritis or Crohn’s disease. + +3. **Interactions with Other Molecules**: + - Ab_sR_IL6 would primarily interact with sIL-6R, preventing it from binding to IL-6. This could impede the formation of the IL-6/sIL-6R complex, potentially reducing downstream signaling through the STAT3 pathway and other associated responses, such as C-reactive protein (CRP) production in the liver. + +4. **Importance in the Biological System Being Modeled**: + - In the context of a model focused on immune regulation, particularly in conditions like Crohn’s disease, targeting sIL-6R with an antibody could be critical in modulating the inflammatory response. By acting on the IL-6 signaling pathway, such an approach could help manage systemic inflammation and related symptoms. + +While there is no specific mention of 'Ab_sR_IL6' in the provided documents, understanding its potential role can be inferred based on known dynamics of IL-6, sIL-6R, and their involvement in immune and inflammatory processes." +mw7becb5fe_8da8_4285_a821_0d77ad811b62,"sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR_IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no specific mention or detailed description of a species or molecule named 'sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, we can infer information about its potential biological role based on general knowledge of similar components in the context of the document, which discusses IL-6 signaling pathways. + +The document prominently features IL-6 (Interleukin-6) and its role in the context of immune regulation, particularly in relation to Crohn’s disease. IL-6 is a cytokine involved in inflammation and immune responses. It signals through two main pathways: classical signaling and trans-signaling. In classical signaling, IL-6 binds to its membrane-bound receptor, IL-6R, and subsequently recruits gp130, leading to the activation of downstream pathways such as the JAK/STAT pathway. In trans-signaling, IL-6 can also bind to a soluble form of its receptor, sIL-6R, allowing it to act on cells that do not express membrane-bound IL-6R. + +Given the emphasis on IL-6 and sIL-6R in the context, 'sR_IL6' could refer to a soluble receptor or a related soluble component in the IL-6 signaling pathway. This type of molecule typically facilitates trans-signaling interactions. It may interact with IL-6 to form a complex that can then engage with another component, sgp130, to modulate signaling. This complex plays a role in regulating immune responses and could have therapeutic implications, especially in diseases like Crohn’s disease where IL-6 signaling is dysregulated. + +In summary, if 'sR_IL6' is indeed related to IL-6 signaling, its biological importance might lie in modulating inflammatory responses through trans-signaling, interacting with IL-6 and possibly other soluble receptors or signaling molecules in this pathway. Its role would be crucial in maintaining homeostasis in immune function and could be a target for therapeutic interventions." +mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca,"gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",gp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, here is the summarized background information about the gp130 species: + +1. **Biological Function**: gp130 is a protein that plays a critical role in signaling pathways, specifically as part of the interleukin-6 (IL-6) signaling pathway. It acts as a key signal transducer and is involved in the formation of a signaling complex with the IL-6 receptor. + +2. **Role in Pathways**: gp130 is an integral component of the signaling complex formed between IL-6 and its soluble receptor, sIL-6Rα. The complex formation is crucial for IL-6 trans-signaling, which is implicated in various inflammatory responses. + +3. **Interactions with Other Molecules**: gp130 interacts with IL-6 and sIL-6Rα to form a hexameric complex that is necessary for initiating the downstream signaling cascade. Soluble gp130 (sgp130) acts as a natural inhibitor by binding to this complex, thereby preventing trans-signaling. + +4. **Importance in the Biological System**: In the context of the system being modeled, soluble gp130 (sgp130) is considered a potential therapeutic agent, especially in conditions like Crohn's disease, due to its ability to inhibit IL-6 trans-signaling. However, the effectiveness of sgp130 is dependent on achieving high and frequent doses, as small alterations in sgp130 levels have minimal impact due to its high baseline concentration relative to IL-6. + +Overall, gp130 is pivotal for IL-6-mediated signaling, and modifications in its activity can potentially modulate inflammatory pathways, making it a significant target in certain therapeutic approaches." +mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9,"R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",R_IL6_gp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context provided, the species named 'R_IL6_gp130' appears to relate to the interleukin-6 (IL-6) signaling pathway, which involves the interaction of IL-6 with its receptor components for signal transduction. Although specific details about this species are not directly provided in the context, we can infer its characteristics and role based on the general knowledge of similar biological components involved in IL-6 signaling: + +1. **Biological Function**: R_IL6_gp130 likely represents a complex involving IL-6, its specific receptor, and the signal transducer gp130. In the IL-6 signaling pathway, gp130 serves as a critical signal transducer that, upon activation by the IL-6/IL-6 receptor complex, initiates intracellular signaling cascades that influence gene expression. + +2. **Role in Pathways**: This species is part of the IL-6 signaling pathway, which can activate the JAK/STAT signaling cascade, resulting in the phosphorylation of STAT3 (Signal Transducer and Activator of Transcription 3). This pathway is crucial in mediating inflammatory responses and plays a role in various physiological and pathological processes, including immune regulation, inflammation, and cell growth. + +3. **Interactions with Other Molecules**: R_IL6_gp130 likely interacts with IL-6 and its soluble receptor (sIL-6R), as well as with gp130. This interaction forms a complex that facilitates signal transduction through the gp130 component, leading to downstream effects such as the activation of STAT3. It can also interact with inhibitors like soluble gp130 (sgp130) or fusion proteins designed to modulate this signaling pathway. + +4. **Importance in the Biological System**: Within the context described, R_IL6_gp130 is important for understanding the dynamics of IL-6 signaling, especially in inflammatory conditions such as Crohn's disease. The IL-6 pathway is targeted for therapeutic intervention, suggesting its significance in disease pathology and treatment. + +In summary, R_IL6_gp130 likely represents a key component of the IL-6 signaling pathway, central to mediating the effects of IL-6 through gp130 in inflammation and immune response, as inferred from the general function of similar complexes." +mw6cce2109_0e32_4dd9_98ec_41173e8ef07d,"Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",Ractive,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there appears to be no specific information about the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' within the text. However, the context discusses the IL-6 signaling pathway and its components, particularly focusing on the interactions between IL-6, sIL-6Rα, and therapeutic antibodies, such as the humanized anti-interleukin 6 receptor antibody (tocilizumab). This suggests a theme centered around immune response regulation, specifically in diseases like rheumatoid arthritis and possibly Crohn's disease. + +In the absence of specific information about 'Ractive', we can infer its potential role based on the discussed biological components. It is likely that 'Ractive' could be involved in the pathways related to cytokine signaling, immune modulation, or therapeutic interactions similar to those of IL-6 or its receptor complex. Its importance in the system may be linked to modulating immune responses or serving as a target or mediator in therapeutic approaches within the context of the mentioned diseases. + +In systems biology modeling, species or molecules like 'Ractive' could be critical for either transmitting signals within a pathway, modifying the activity of other molecules, or acting as a checkpoint or target for drugs designed to alter biological responses in conditions like Crohn's disease or rheumatoid arthritis." +mw2b255f94_8018_4b99_bde8_918eeac45446,"STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",STAT3,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, the species 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is likely referring to the well-known protein STAT3, a signal transducer and activator of transcription 3. Here is the relevant background information about STAT3: + +1. **Biological Function**: + - STAT3 is involved in the phosphorylation process as part of cell signaling. Phosphorylated STAT3 (pSTAT3) is indicative of its active state, which can translocate to the nucleus to act as a transcription factor. + - It plays a crucial role in relaying signals from cytokine receptors, like the IL-6 receptor complex, to the nucleus, influencing gene expression. + +2. **Role in Pathways**: + - STAT3 is a central component of the JAK-STAT signaling pathway. Once activated, it typically mediates the effects of cytokines, such as IL-6, contributing to various cellular responses, including growth, differentiation, and survival. + - The context mentions its involvement in pathways activated by IL-6, a cytokine that triggers immune responses, inflammation, and acute-phase reactions. + +3. **Interactions with Other Molecules**: + - STAT3 gets activated by cytokines binding to their respective receptors, leading to JAK kinases' activation, which subsequently phosphorylates STAT3. + - It interacts with components of the IL-6 receptor family, specifically affecting the pathways involving IL-6 trans-signaling. + - The context also suggests interactions involving sIL-6R (a soluble IL-6 receptor) and sgp130 (a soluble form of the co-receptor gp130), where pSTAT3 acts in various compartments like the GI tract and liver depending on cytokine signaling. + +4. **Importance in the Biological System**: + - STAT3 is important in modeling biological systems that involve immune responses or inflammation, such as in the context of Crohn's disease, as indicated by increased pSTAT3 levels in serum and tissues affected by the disease. + - Its role as a transcription factor makes it key in regulating downstream gene expression that could contribute to disease pathology and the body's response to inflammation. + +In summary, although there is no direct mention of a species specifically labeled 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' in the document, the general characteristics and functions of STAT3 can be inferred based on common scientific knowledge and the provided context about IL-6 signaling and related pathways." +mw48867e93_f170_44e8_ac7a_185b23e1bf3b,"pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",pSTAT3,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context provided, specific information about the biological species 'pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is not explicitly detailed. However, we can infer its role and significance based on the general knowledge about pSTAT3 and its involvement in biological processes. + +1. **Biological Function:** + - pSTAT3, or phosphorylated STAT3, is a form of Signal Transducer and Activator of Transcription 3 (STAT3) that becomes activated through phosphorylation. This activation enables pSTAT3 to translocate to the cell nucleus, where it functions as a transcription factor, promoting the expression of various genes involved in cell growth, survival, and differentiation. + +2. **Role in Pathways:** + - In the context described, pSTAT3 is associated with IL-6 signaling, which involves classical and trans-signaling pathways. IL-6 is a cytokine involved in immune response, and its interaction with receptors such as IL-6R and gp130 leads to the activation of JAK kinases and subsequent phosphorylation of STAT3 (pSTAT3). This signaling cascade is crucial in mediating responses to inflammation and stress. + +3. **Interactions with Other Molecules:** + - pSTAT3 interacts with the IL-6 receptor complex, including sIL-6R (soluble IL-6 receptor) and sgp130 (soluble gp130). The complex formation and subsequent signaling facilitate various downstream effects. pSTAT3 is known to regulate the expression of suppressor of cytokine signaling (SOCS) proteins and other gene products involved in modulating immune responses. + +4. **Importance in the Biological System Being Modeled:** + - pSTAT3 plays a critical role in inflammatory responses, as highlighted by its reported increase in serum concentrations in conditions like Crohn’s disease. It is involved in the transcriptional regulation of acute-phase proteins such as C-reactive protein (CRP) and other gene products that are significant in the immune response and inflammation within the gastrointestinal tract and liver. + +This inferred information helps underscore the importance of pSTAT3 in immune modulation and its potential implications in inflammatory diseases, even though specific details about its ID-specific characteristics in the context were not provided." +mw0083d743_836f_4238_a17f_4602193d5bc0,geneProduct,geneProduct,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The provided context from the document does not include specific details about the biological species or molecule identified as 'geneProduct' with the ID: mw0083d743_836f_4238_a17f_4602193d5bc0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. There is no explicit mention of this molecule's biological function, role in pathways, interactions with other molecules, or its importance in the biological system being modeled. + +Based on the context, which predominantly discusses interleukin-6 (IL-6) pathways, receptors, and related molecules (e.g., sIL-6R, gp130, and sgp130), we can infer that 'geneProduct' might be related to the IL-6 signaling pathway or another signaling molecule involved in inflammatory or immune responses. In systems biologically concerned with inflammation or cytokine signaling, such gene products might typically be involved in cell signaling cascades, playing roles in activating transcription factors, interacting with receptors or co-receptors, and affecting the expression of downstream genes important for cellular responses. + +Since specific data is not available, hypothetical pathways could involve roles similar to those of IL-6 or its receptors—modulating inflammatory responses, and participating in acute phase reactions, including CRP production in the liver. Gene products in such pathways often interact with other cytokines, receptors, and intracellular signaling proteins to exert their effects, potentially influencing processes like cell proliferation, differentiation, and survival." +mwd31f52cc_04e7_40e0_885f_c7b2d9e62215,"sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context provided, there is no explicit mention of the species 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' directly in the excerpts. However, we can infer some related information using general knowledge and by examining the related components and interactions in the context shared. + +The context revolves around the interaction and dynamics involving the Interleukin-6 (IL-6) signaling pathway, soluble IL-6 receptor (sIL-6R), and the involvement of other molecules like sgp130. + +### Inferred Background Information about 'sR': + +1. **Biological Function:** + - In the context of cytokine signaling, receptors like sR are generally involved in recognizing and binding to specific signaling molecules (e.g., cytokines such as IL-6) to facilitate their biological functions. Therefore, 'sR' could act as a receptor or part of a receptor complex in signaling pathways. + +2. **Role in Pathways:** + - Given the presence of IL-6 and its receptor dynamics (e.g., IL-6/sIL-6R complex) in the context, 'sR' might participate in cytokine signaling pathways, potentially serving as a modulator that enhances or inhibits signal transduction depending on its specific interactions with IL-6 or other pathway components like sgp130. + +3. **Interactions with Other Molecules:** + - The sIL-6R forms complexes with IL-6, which then interact with membrane-bound receptors to initiate signaling cascades like the activation of STAT3. 'sR' might potentially interact similarly, indicating a critical role in modifying the intensity or outcome of the signaling process. + +4. **Importance in the Biological System Being Modeled:** + - The balance of soluble receptors and cytokines (such as IL-6/sIL-6R) and their interactions with other molecules (e.g., sgp130) are essential for controlling inflammatory responses and other downstream effects (e.g., CRP production in the liver). + - Given this, 'sR' could play a pivotal regulatory role, affecting the system's sensitivity to changes in cytokine levels and potentially serving as a target for therapeutic interventions. + +### Conclusion: + +While the provided document excerpts do not explicitly detail 'sR's identity or function, its inferred associations with key players like IL-6, sIL-6R, and sgp130 suggest a role in cytokine signaling modulation, particularly in pathways relevant to inflammation and immune response. For specific molecular functions and pathway roles, further examination of full-length documents or additional sources would be required." +mw2c9b0499_3325_4394_8af3_bbf653a944a0,"IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context and general knowledge, the species named 'IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' is likely referring to Interleukin-6 (IL-6), a cytokine involved in various biological functions and pathways. Here is a summary of its roles and significance: + +1. **Biological Function:** + - IL-6 is a multifunctional cytokine that plays a critical role in immune response regulation, inflammation, and hematopoiesis. + - It is known to be a mediator of fever and of the acute phase response. + +2. **Role in Pathways:** + - IL-6 signaling occurs via two main pathways: the classical signaling pathway and the trans-signaling pathway. + - The classical pathway involves IL-6 binding to a membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of IL-6Rα (sIL-6Rα). + - Both pathways converge on a signal transduction cascade that activates Janus kinase (Jak) proteins and leads to the phosphorylation of signal transducer and activator of transcription 3 (STAT3). + +3. **Interactions with Other Molecules:** + - IL-6 interacts with its receptor IL-6Rα (either membrane-bound or soluble) and forms a complex that recruits the gp130 coreceptor. + - This interaction is crucial for activating downstream signaling pathways that are involved in immune responses. + +4. **Importance in the Biological System:** + - IL-6 is particularly important in inflammatory diseases such as Crohn's disease, where it contributes to enhanced T-cell survival and resistance to apoptosis in the intestinal mucosa, as well as elevated chemokine secretion. + - It plays a significant role in the pathophysiology of autoimmune diseases and chronic inflammatory conditions, making it a target for therapeutic interventions such as with specific antibodies like tocilizumab. + +In summary, IL-6 is a central cytokine in immune regulation and inflammatory processes, which makes it a pivotal part of the biological system being modeled, particularly in the context of diseases like Crohn's disease." +mwd65b5b39_dc1b_4e77_a999_67277a880e5e,"sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sgp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, here is the background information about the species 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)': + +### Biological Function: +sgp130, known here as a species variant, reflects a biological molecule related to the inhibition of IL-6 trans-signaling. It specifically refers to a fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is designed to inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex. + +### Role in Pathways: +sgp130 plays a role in pathways involving the interleukin-6 (IL-6) signaling cascade. It specifically targets the IL-6/sIL-6Rα complex, blocking the trans-signaling pathway that can contribute to inflammatory responses, such as those observed in Crohn’s disease. + +### Interactions with Other Molecules: +sgp130 interacts with the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc binds this complex with the same affinity as natural sgp130, thus inhibiting the signaling pathways mediated by IL-6. + +### Importance in the Biological System: +sgp130 appears to be of limited effect in altering the steady-state values of certain biomarkers unless present in large quantities. It exists in excess compared to free IL-6, leading to minimal effect from small perturbations in its levels. Hence, any significant observable effects require substantial changes in sgp130 concentrations. + +Despite its biological function, the context suggests that sgp130-based therapeutic strategies may not be as robust as anticipated. The sensitivity analysis indicated that the output biomarkers are less affected by sgp130 levels, making IL-6 and sIL-6Rα more potent targets for intervention in the studied system. This contributes to understanding its therapeutic potential limitations, particularly in addressing diseases like Crohn's where IL-6 signaling is implicated." +mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3,"sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR_IL6_sgp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The species sR_IL6_sgp130, identified as mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 within the context provided, appears to involve components related to interleukin-6 (IL-6) signaling pathways. Here is the summary of the background based on the given context and general knowledge: + +### Biological Function +- **Fusion Protein**: The document mentions a fusion protein involving sgp130, which combines the extracellular portion of the gp130 protein with the Fc region of human IgG1. This fusion protein, known as sgp130Fc, is designed to inhibit IL-6 trans-signaling in cells. + +### Role in Pathways +- **IL-6 Trans-Signaling**: The primary role of sgp130Fc is to inhibit IL-6 trans-signaling. In the IL-6 signaling pathway, IL-6 can signal through its receptor complex involving IL-6R and gp130, leading to downstream effects such as the activation of STAT3 transcription factors. The fusion protein acts to prevent this signaling pathway by binding to the IL-6/sIL-6Rα complex. +- **Simulations in Crohn’s Disease**: The sgp130Fc protein is being studied for its therapeutic potential in inflammatory conditions like Crohn’s disease, where IL-6 signaling plays a significant role. + +### Interactions with Other Molecules +- **Binding with IL-6/sIL-6Rα Complex**: The sgp130Fc is assumed to bind with the IL-6/sIL-6Rα complex with affinities similar to natural sgp130. The presence of sgp130Fc in large quantities suggests it primarily functions by excess binding to this complex, thereby preventing excessive IL-6 signaling. + +### Importance in the Biological System +- **Therapeutic Potential**: The document outlines the use of sgp130Fc as a potential therapeutic intervention in diseases with aberrant IL-6 signaling, such as Crohn’s disease. It has been shown to only be effective at very high doses due to its interaction landscape. +- **Limited Systemic Impact**: Due to high baseline levels of sgp130 compared to IL-6, small changes in sgp130 do not significantly affect the system, implying its role predominantly emerges under conditions requiring high-dose applications or alterations. + +Overall, while the document primarily discusses the use of a related molecule (sgp130Fc), it emphasizes the relevance of sgp130 interactions within IL-6-related pathways, underscoring its importance in modulating immune and inflammatory responses within certain pathological contexts." +mwf7796221_1fea_4274_a93e_c00adbf5778c,"Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no specific detailed information available about the species or molecule 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' with the ID mwf7796221_1fea_4274_a93e_c00adbf5778c. However, from the context and general knowledge, we can infer the following: + +1. **Biological Function**: The document references serum antibody (Ab) concentrations in nmol/l, which suggests that 'Ab' likely stands for an antibody. Antibodies are proteins produced by the immune system to identify and neutralize pathogens such as bacteria and viruses. + +2. **Role in Pathways**: The context mentions anti-IL-6/sIL-6Rα interactions. Antibodies targeting the interleukin-6 (IL-6) pathway are typically used in treatments to modulate immune responses, particularly in inflammatory conditions. They can bind to IL-6 or its receptor to inhibit the downstream signaling pathway. + +3. **Interactions with Other Molecules**: The document discusses the anti-IL-6 Ab's effect in relation to IL-6 and sIL-6Rα. This suggests that the antibody in question interacts specifically with these cytokines or cytokine receptors, playing a role in reducing inflammation by interfering with the IL-6 signaling pathway. + +4. **Importance in the Biological System**: The antibody’s importance seems to be related to its therapeutic role in modulating the immune response, particularly in diseases involving heavy inflammation. This can include conditions like inflammatory bowel diseases or other autoimmune disorders, where targeting IL-6 or its receptor can have significant therapeutic effects. + +In summary, based on the context and typical characteristics of antibodies in similar biological systems, 'Ab' is likely an antibody involved in targeting the IL-6 signaling pathway, important for managing inflammatory responses in various conditions." +mw5d764bb8_5693_4ac8_9557_f65992cc5eb0,"Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab_sR,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no specific mention or details about the species named 'Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, I can infer potential roles and functions based on adjacent biological components and typical interactions within such systems, especially considering the discussion around IL-6 pathways and related molecules in the context. + +1. **Biological Function**: In this particular study context, sIL-6R (soluble Interleukin-6 receptor) and IL-6 (a cytokine involved in inflammation and immune responses) are key components. Ab_sR might refer to an antibody-related soluble receptor component or variant. If related to IL-6/sIL-6R pathways, its function could involve modulation of immune responses or inflammation via binding interactions. + +2. **Role in Pathways**: The surrounding context heavily discusses the interaction of IL-6 with its receptor and the subsequent signaling pathways, such as the Jak-STAT pathway (notably leading to STAT3 activation), indicating a role in cytokine-receptor interactions. Ab_sR could interact within these pathways, perhaps as an intermediary or a modulator influencing signal transduction. + +3. **Interactions with Other Molecules**: If analogous to sIL-6R or anti-IL-6 therapeutic antibodies, Ab_sR might interact with IL-6, potentially modulating its effects by altered binding dynamics or competitive inhibition. Such interactions could influence downstream signaling events leading to transcriptional changes (e.g., expression of SOCS or CRP). + +4. **Importance in Biological System Being Modeled**: In systems modeling inflammatory responses, any component similar to an antibody interacting with cytokines like IL-6 is critical. It could predictively simulate treatment outcomes for inflammatory diseases or evaluate drug efficacy (e.g., CRP suppression in inflammatory cases). Ab_sR may hold similar significance if it's part of experimental or theoretical models assessing cytokine network modulation. + +While these are educated guesses based on typical roles and interactions of analogous proteins within such biological systems, exact functions and roles of Ab_sR would be best determined by specifics from the cited source text." +mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2,"Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab_sR_IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2) does not have specific background information provided explicitly in the context you shared. However, I can infer potential characteristics based on general knowledge about similar components. + +### Inferred Background Information: + +1. **Biological Function:** + - 'Ab_sR_IL6' likely refers to an antibody ('Ab') targeting the soluble form of the interleukin-6 receptor (sIL-6R). This suggests it is involved in neutralizing or modulating the biological effects of sIL-6R, potentially inhibiting its interaction with interleukin-6 (IL-6). + +2. **Role in Pathways:** + - The context described the targeting of the IL-6/sIL-6R complex as a treatment strategy for conditions involving excessive IL-6 signaling, such as Crohn's disease. 'Ab_sR_IL6' might play a role in suppressing IL-6-mediated pathways, thereby reducing inflammation or immune responses associated with diseases like Crohn's disease or rheumatoid arthritis. + +3. **Interactions with Other Molecules:** + - Interacts with sIL-6R, preventing the formation of the IL-6/sIL-6R complex. This interaction would diminish the activity of the classical and trans-signaling pathways mediated by IL-6, leading to reduced activation of downstream signaling molecules like STAT3 and associated gene transcription. + +4. **Importance in the Biological System Being Modeled:** + - Its importance lies in modulating inflammation by impacting IL-6 signaling. As IL-6 is crucial in immune response modulation, controlling its activity can lead to therapeutic benefits in diseases characterized by inflammation and immune dysregulation. + +Broadly, 'Ab_sR_IL6' serves as a critical component in therapeutic models aiming to attenuate aberrant IL-6 signaling pathways in immune-mediated diseases." +mwbc2f5464_81e5_43fd_8b39_f5a2756af72f,"Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)",Ab,mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87,"The provided context does not contain direct information specifically about the species 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, from the available information, we can infer some details based on the general context and related biological components mentioned: + +1. **Biological Function**: The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects like bacteria and viruses. They play a crucial role in targeting specific antigens for the immune response. + +2. **Role in Pathways**: The context discusses the interaction between anti-IL-6 antibodies and IL-6/sIL-6Rα complex. IL-6 is a cytokine involved in inflammation and infection responses. Hence, antibodies targeting IL-6 pathways are often part of therapeutic interventions for inflammatory diseases. + +3. **Interactions with Other Molecules**: The document mentions the targeting of IL-6 and IL-6/sIL-6Rα complexes, suggesting that this antibody interacts with these molecules, likely inhibiting their function to reduce inflammation as indicated by the suppression of CRP (C-reactive protein), a marker of inflammation. + +4. **Importance in the Biological System Being Modeled**: The antibody's role appears to be significant in modulating inflammatory responses by targeting key molecular pathways involving IL-6 and its receptors. This indicates its potential therapeutic value in treating conditions where IL-6 is implicated, such as autoimmune or inflammatory diseases. + +In summary, while the antibody 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)' is not directly described in the context, inferred information suggests it likely functions as an IL-6 pathway inhibitor in an inflammatory response model, emphasizing its role in treatment strategies aimed at modulating immune responses." From 8266302f321f8fb0afbb8f7bafd983eff233059c Mon Sep 17 00:00:00 2001 From: ShengZhaoDE Date: Fri, 7 Mar 2025 13:16:45 +0100 Subject: [PATCH 10/14] update --- notebook/sbml_rag_notebook.ipynb | 1674 +++++++++++++++++++++++++++++- 1 file changed, 1631 insertions(+), 43 deletions(-) diff --git a/notebook/sbml_rag_notebook.ipynb b/notebook/sbml_rag_notebook.ipynb index 5c7f2cef..554a3483 100644 --- a/notebook/sbml_rag_notebook.ipynb +++ b/notebook/sbml_rag_notebook.ipynb @@ -110,9 +110,51 @@ "Loading and processing PDF...\n", "Extracting keywords from PDF...\n", "Parsing SBML model for species...\n", - "Limiting processing to 1 species (out of 44 total)\n", - "Extracting background information for 1 species...\n", - "Processing species 1/1: IL6\n" + "Extracting background information for 44 species...\n", + "Processing species 1/44: IL6\n", + "Processing species 2/44: sgp130\n", + "Processing species 3/44: sR_IL6_sgp130\n", + "Processing species 4/44: CRP\n", + "Processing species 5/44: sR\n", + "Processing species 6/44: sR_IL6\n", + "Processing species 7/44: Ab\n", + "Processing species 8/44: Ab_sR\n", + "Processing species 9/44: Ab_sR_IL6\n", + "Processing species 10/44: CRP Suppression (%)\n", + "Processing species 11/44: CRP (% of baseline)\n", + "Processing species 12/44: gp130\n", + "Processing species 13/44: R_IL6_gp130\n", + "Processing species 14/44: sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + "Processing species 15/44: R\n", + "Processing species 16/44: IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + "Processing species 17/44: R_IL6\n", + "Processing species 18/44: Ractive\n", + "Processing species 19/44: STAT3\n", + "Processing species 20/44: pSTAT3\n", + "Processing species 21/44: CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + "Processing species 22/44: sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + "Processing species 23/44: CRPExtracellular\n", + "Processing species 24/44: sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + "Processing species 25/44: sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + "Processing species 26/44: Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + "Processing species 27/44: Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + "Processing species 28/44: Ab_R\n", + "Processing species 29/44: Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + "Processing species 30/44: sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + "Processing species 31/44: gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)\n", + "Processing species 32/44: R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)\n", + "Processing species 33/44: Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)\n", + "Processing species 34/44: STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)\n", + "Processing species 35/44: pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)\n", + "Processing species 36/44: geneProduct\n", + "Processing species 37/44: sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + "Processing species 38/44: IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + "Processing species 39/44: sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + "Processing species 40/44: sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + "Processing species 41/44: Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + "Processing species 42/44: Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + "Processing species 43/44: Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + "Processing species 44/44: Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)\n" ] } ], @@ -147,24 +189,24 @@ "PDF Keywords:\n", "1. Crohns disease\n", "2. IL-6\n", - "3. T-cells\n", - "4. apoptosis\n", - "5. inflammation\n", - "6. IL-6Rα\n", - "7. sIL-6Rα\n", - "8. gp130\n", - "9. Jak\n", - "10. STAT3\n", - "11. CRP\n", - "12. hepatocytes\n", - "13. leukocytes\n", + "3. IL-6R\n", + "4. sIL-6R\n", + "5. CRP\n", + "6. gp130\n", + "7. Jak\n", + "8. STAT3\n", + "9. T-cells\n", + "10. hepatocytes\n", + "11. apoptosis\n", + "12. inflammation\n", + "13. GI tract\n", "14. sgp130\n", "15. tocilizumab\n", - "16. GI tract\n", - "17. liver\n", - "18. monoclonal antibodies\n", - "19. SOCS\n", - "20. circulation\n" + "16. cytokines\n", + "17. Janus kinase\n", + "18. lamina propria\n", + "19. leukocytes\n", + "20. chemokine\n" ] } ], @@ -221,21 +263,540 @@ " IL6\n", " IL6\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " IL6, or Interleukin 6, is a cytokine that play...\n", + " The provided context outlines the biological f...\n", + " \n", + " \n", + " 1\n", + " mwbbbce920_e8dd_4320_9386_fc94bfb2fc99\n", + " sgp130\n", + " sgp130\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " Based on the context provided, sgp130 is a bio...\n", + " \n", + " \n", + " 2\n", + " mw810ff751_fa4e_4143_bd50_169b3e325e1e\n", + " sR_IL6_sgp130\n", + " sR_IL6_sgp130\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " Based on the provided context from the documen...\n", + " \n", + " \n", + " 3\n", + " mw114aa90f_5f5b_4fe8_9406_361c8489b6a1\n", + " CRP\n", + " CRP\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " The term 'CRP' within the context provided ref...\n", + " \n", + " \n", + " 4\n", + " mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc\n", + " sR\n", + " sR\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " Based on the provided context, the species nam...\n", + " \n", + " \n", + " 5\n", + " mw03db56ac_8dc6_4931_ae82_fef706d2ee3d\n", + " sR_IL6\n", + " sR_IL6\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " The species labeled 'sR_IL6' in the context pr...\n", + " \n", + " \n", + " 6\n", + " mwf345ed7a_0622_403c_b816_c8749a2c9ded\n", + " Ab\n", + " Ab\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " Based on the provided documents, there isn't d...\n", + " \n", + " \n", + " 7\n", + " mw1da111f2_a036_4392_8512_015005bdcbb7\n", + " Ab_sR\n", + " Ab_sR\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " The specific species 'Ab_sR' (ID: mw1da111f2_a...\n", + " \n", + " \n", + " 8\n", + " mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac\n", + " Ab_sR_IL6\n", + " Ab_sR_IL6\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " The context provided does not directly specify...\n", + " \n", + " \n", + " 9\n", + " CRP_Suppression___\n", + " CRP Suppression (%)\n", + " CRP Suppression (%)\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " Based on the context provided, \"CRP Suppressio...\n", + " \n", + " \n", + " 10\n", + " CRP____of_baseline\n", + " CRP (% of baseline)\n", + " CRP (% of baseline)\n", + " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", + " The term \"CRP (% of baseline)\" is referring to...\n", + " \n", + " \n", + " 11\n", + " mw80848184_e2dd_47ce_86d7_7a21479342bd\n", + " gp130\n", + " gp130\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " The species named 'gp130' refers to a protein ...\n", + " \n", + " \n", + " 12\n", + " mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a\n", + " R_IL6_gp130\n", + " R_IL6_gp130\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " The species named 'R_IL6_gp130', based on its ...\n", + " \n", + " \n", + " 13\n", + " mw4638f126_8cb8_4021_ab41_6ae195743ba0\n", + " sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e...\n", + " sR_IL6\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " Based on the provided context and general know...\n", + " \n", + " \n", + " 14\n", + " mw10315fa3_6f13_4618_bda8_a8694bd3c374\n", + " R\n", + " R\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " Given the context provided, the information ab...\n", + " \n", + " \n", + " 15\n", + " mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1\n", + " IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + " IL6\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " Based on the context provided, the species ref...\n", + " \n", + " \n", + " 16\n", + " mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83\n", + " R_IL6\n", + " R_IL6\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " Based on the context provided, there is no spe...\n", + " \n", + " \n", + " 17\n", + " mw0eb6c959_d408_45a0_a450_928b8c5876bb\n", + " Ractive\n", + " Ractive\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " The context provided does not include specific...\n", + " \n", + " \n", + " 18\n", + " mw42054cd7_17af_46da_970c_7f99151906ad\n", + " STAT3\n", + " STAT3\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " Based on the provided context and general know...\n", + " \n", + " \n", + " 19\n", + " mw39c2e431_fdc3_4964_be29_6ca856620b1b\n", + " pSTAT3\n", + " pSTAT3\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " The context provided mainly revolves around th...\n", + " \n", + " \n", + " 20\n", + " mwd5313618_89eb_4c8c_bc82_66f10f966349\n", + " CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + " CRP\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " The species referred to as \"CRP (mw88ca8d9a_f5...\n", + " \n", + " \n", + " 21\n", + " mw2e464cf3_a09c_4b7c_9f3c_06720016a48e\n", + " sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + " sR\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " Based on the provided context, specific inform...\n", + " \n", + " \n", + " 22\n", + " mw36ea78c1_ed71_4def_96d3_857a442d7195\n", + " CRPExtracellular\n", + " CRPExtracellular\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " The species named 'CRPExtracellular' likely re...\n", + " \n", + " \n", + " 23\n", + " mw147d30ec_478e_4090_b496_128a131d29eb\n", + " sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e...\n", + " sgp130\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " The species referred to as 'sgp130 (mw88ca8d9a...\n", + " \n", + " \n", + " 24\n", + " mwab41493c_6349_45f1_a226_3030cfed0e06\n", + " sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f...\n", + " sR_IL6_sgp130\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " Based on the provided context, the species 'sR...\n", + " \n", + " \n", + " 25\n", + " mwf405687b_7401_44ec_a0d6_4a2b35c13e8a\n", + " Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,...\n", + " Ab_sR\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " Based on the provided context, no specific inf...\n", + " \n", + " \n", + " 26\n", + " mw3667a5e1_02c9_44a0_acb4_b0431faa822d\n", + " Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", + " Ab\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " Based on the context provided, there isn't dir...\n", + " \n", + " \n", + " 27\n", + " mw772cbf20_3fc1_4800_ae59_77884f1ae333\n", + " Ab_R\n", + " Ab_R\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " The document provided does not explicitly ment...\n", + " \n", + " \n", + " 28\n", + " mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf\n", + " Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a...\n", + " Ab_sR_IL6\n", + " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", + " The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9...\n", + " \n", + " \n", + " 29\n", + " mw7becb5fe_8da8_4285_a821_0d77ad811b62\n", + " sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5...\n", + " sR_IL6\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the provided context, there is no spe...\n", + " \n", + " \n", + " 30\n", + " mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca\n", + " gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,...\n", + " gp130\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the provided context, here is the sum...\n", + " \n", + " \n", + " 31\n", + " mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9\n", + " R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fc...\n", + " R_IL6_gp130\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the context provided, the species nam...\n", + " \n", + " \n", + " 32\n", + " mw6cce2109_0e32_4dd9_98ec_41173e8ef07d\n", + " Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b...\n", + " Ractive\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the provided context, there appears t...\n", + " \n", + " \n", + " 33\n", + " mw2b255f94_8018_4b99_bde8_918eeac45446\n", + " STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,...\n", + " STAT3\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the provided context, the species 'ST...\n", + " \n", + " \n", + " 34\n", + " mw48867e93_f170_44e8_ac7a_185b23e1bf3b\n", + " pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5...\n", + " pSTAT3\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the context provided, specific inform...\n", + " \n", + " \n", + " 35\n", + " mw0083d743_836f_4238_a17f_4602193d5bc0\n", + " geneProduct\n", + " geneProduct\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " The provided context from the document does no...\n", + " \n", + " \n", + " 36\n", + " mwd31f52cc_04e7_40e0_885f_c7b2d9e62215\n", + " sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + " sR\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the context provided, there is no exp...\n", + " \n", + " \n", + " 37\n", + " mw2c9b0499_3325_4394_8af3_bbf653a944a0\n", + " IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + " IL6\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the provided context and general know...\n", + " \n", + " \n", + " 38\n", + " mwd65b5b39_dc1b_4e77_a999_67277a880e5e\n", + " sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5...\n", + " sgp130\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the provided context, here is the bac...\n", + " \n", + " \n", + " 39\n", + " mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3\n", + " sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3...\n", + " sR_IL6_sgp130\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " The species sR_IL6_sgp130, identified as mw633...\n", + " \n", + " \n", + " 40\n", + " mwf7796221_1fea_4274_a93e_c00adbf5778c\n", + " Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", + " Ab\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the provided context, there is no spe...\n", + " \n", + " \n", + " 41\n", + " mw5d764bb8_5693_4ac8_9557_f65992cc5eb0\n", + " Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,...\n", + " Ab_sR\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " Based on the provided context, there is no spe...\n", + " \n", + " \n", + " 42\n", + " mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2\n", + " Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb1...\n", + " Ab_sR_IL6\n", + " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", + " The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4...\n", + " \n", + " \n", + " 43\n", + " mwbc2f5464_81e5_43fd_8b39_f5a2756af72f\n", + " Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)\n", + " Ab\n", + " mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87\n", + " The provided context does not contain direct i...\n", " \n", " \n", "\n", "" ], "text/plain": [ - " id name original_name \\\n", - "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 IL6 \n", + " id \\\n", + "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b \n", + "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 \n", + "2 mw810ff751_fa4e_4143_bd50_169b3e325e1e \n", + "3 mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 \n", + "4 mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc \n", + "5 mw03db56ac_8dc6_4931_ae82_fef706d2ee3d \n", + "6 mwf345ed7a_0622_403c_b816_c8749a2c9ded \n", + "7 mw1da111f2_a036_4392_8512_015005bdcbb7 \n", + "8 mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac \n", + "9 CRP_Suppression___ \n", + "10 CRP____of_baseline \n", + "11 mw80848184_e2dd_47ce_86d7_7a21479342bd \n", + "12 mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a \n", + "13 mw4638f126_8cb8_4021_ab41_6ae195743ba0 \n", + "14 mw10315fa3_6f13_4618_bda8_a8694bd3c374 \n", + "15 mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 \n", + "16 mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 \n", + "17 mw0eb6c959_d408_45a0_a450_928b8c5876bb \n", + "18 mw42054cd7_17af_46da_970c_7f99151906ad \n", + "19 mw39c2e431_fdc3_4964_be29_6ca856620b1b \n", + "20 mwd5313618_89eb_4c8c_bc82_66f10f966349 \n", + "21 mw2e464cf3_a09c_4b7c_9f3c_06720016a48e \n", + "22 mw36ea78c1_ed71_4def_96d3_857a442d7195 \n", + "23 mw147d30ec_478e_4090_b496_128a131d29eb \n", + "24 mwab41493c_6349_45f1_a226_3030cfed0e06 \n", + "25 mwf405687b_7401_44ec_a0d6_4a2b35c13e8a \n", + "26 mw3667a5e1_02c9_44a0_acb4_b0431faa822d \n", + "27 mw772cbf20_3fc1_4800_ae59_77884f1ae333 \n", + "28 mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf \n", + "29 mw7becb5fe_8da8_4285_a821_0d77ad811b62 \n", + "30 mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca \n", + "31 mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9 \n", + "32 mw6cce2109_0e32_4dd9_98ec_41173e8ef07d \n", + "33 mw2b255f94_8018_4b99_bde8_918eeac45446 \n", + "34 mw48867e93_f170_44e8_ac7a_185b23e1bf3b \n", + "35 mw0083d743_836f_4238_a17f_4602193d5bc0 \n", + "36 mwd31f52cc_04e7_40e0_885f_c7b2d9e62215 \n", + "37 mw2c9b0499_3325_4394_8af3_bbf653a944a0 \n", + "38 mwd65b5b39_dc1b_4e77_a999_67277a880e5e \n", + "39 mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 \n", + "40 mwf7796221_1fea_4274_a93e_c00adbf5778c \n", + "41 mw5d764bb8_5693_4ac8_9557_f65992cc5eb0 \n", + "42 mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2 \n", + "43 mwbc2f5464_81e5_43fd_8b39_f5a2756af72f \n", "\n", - " compartment \\\n", - "0 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + " name original_name \\\n", + "0 IL6 IL6 \n", + "1 sgp130 sgp130 \n", + "2 sR_IL6_sgp130 sR_IL6_sgp130 \n", + "3 CRP CRP \n", + "4 sR sR \n", + "5 sR_IL6 sR_IL6 \n", + "6 Ab Ab \n", + "7 Ab_sR Ab_sR \n", + "8 Ab_sR_IL6 Ab_sR_IL6 \n", + "9 CRP Suppression (%) CRP Suppression (%) \n", + "10 CRP (% of baseline) CRP (% of baseline) \n", + "11 gp130 gp130 \n", + "12 R_IL6_gp130 R_IL6_gp130 \n", + "13 sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e... sR_IL6 \n", + "14 R R \n", + "15 IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) IL6 \n", + "16 R_IL6 R_IL6 \n", + "17 Ractive Ractive \n", + "18 STAT3 STAT3 \n", + "19 pSTAT3 pSTAT3 \n", + "20 CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) CRP \n", + "21 sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) sR \n", + "22 CRPExtracellular CRPExtracellular \n", + "23 sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e... sgp130 \n", + "24 sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f... sR_IL6_sgp130 \n", + "25 Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,... Ab_sR \n", + "26 Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) Ab \n", + "27 Ab_R Ab_R \n", + "28 Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a... Ab_sR_IL6 \n", + "29 sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5... sR_IL6 \n", + "30 gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,... gp130 \n", + "31 R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fc... R_IL6_gp130 \n", + "32 Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b... Ractive \n", + "33 STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,... STAT3 \n", + "34 pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5... pSTAT3 \n", + "35 geneProduct geneProduct \n", + "36 sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) sR \n", + "37 IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) IL6 \n", + "38 sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5... sgp130 \n", + "39 sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3... sR_IL6_sgp130 \n", + "40 Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) Ab \n", + "41 Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,... Ab_sR \n", + "42 Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb1... Ab_sR_IL6 \n", + "43 Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4) Ab \n", "\n", - " background \n", - "0 IL6, or Interleukin 6, is a cytokine that play... " + " compartment \\\n", + "0 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "1 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "2 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "3 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "4 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "5 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "6 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "7 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "8 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "9 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "10 mw53ffe9e6_beef_45c4_90a5_a79197ed506e \n", + "11 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "12 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "13 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "14 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "15 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "16 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "17 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "18 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "19 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "20 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "21 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "22 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "23 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "24 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "25 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "26 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "27 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "28 mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e \n", + "29 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "30 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "31 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "32 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "33 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "34 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "35 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "36 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "37 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "38 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "39 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "40 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "41 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "42 mwe9501423_9fb4_494b_b5b6_288f3fcb17b5 \n", + "43 mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87 \n", + "\n", + " background \n", + "0 The provided context outlines the biological f... \n", + "1 Based on the context provided, sgp130 is a bio... \n", + "2 Based on the provided context from the documen... \n", + "3 The term 'CRP' within the context provided ref... \n", + "4 Based on the provided context, the species nam... \n", + "5 The species labeled 'sR_IL6' in the context pr... \n", + "6 Based on the provided documents, there isn't d... \n", + "7 The specific species 'Ab_sR' (ID: mw1da111f2_a... \n", + "8 The context provided does not directly specify... \n", + "9 Based on the context provided, \"CRP Suppressio... \n", + "10 The term \"CRP (% of baseline)\" is referring to... \n", + "11 The species named 'gp130' refers to a protein ... \n", + "12 The species named 'R_IL6_gp130', based on its ... \n", + "13 Based on the provided context and general know... \n", + "14 Given the context provided, the information ab... \n", + "15 Based on the context provided, the species ref... \n", + "16 Based on the context provided, there is no spe... \n", + "17 The context provided does not include specific... \n", + "18 Based on the provided context and general know... \n", + "19 The context provided mainly revolves around th... \n", + "20 The species referred to as \"CRP (mw88ca8d9a_f5... \n", + "21 Based on the provided context, specific inform... \n", + "22 The species named 'CRPExtracellular' likely re... \n", + "23 The species referred to as 'sgp130 (mw88ca8d9a... \n", + "24 Based on the provided context, the species 'sR... \n", + "25 Based on the provided context, no specific inf... \n", + "26 Based on the context provided, there isn't dir... \n", + "27 The document provided does not explicitly ment... \n", + "28 The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9... \n", + "29 Based on the provided context, there is no spe... \n", + "30 Based on the provided context, here is the sum... \n", + "31 Based on the context provided, the species nam... \n", + "32 Based on the provided context, there appears t... \n", + "33 Based on the provided context, the species 'ST... \n", + "34 Based on the context provided, specific inform... \n", + "35 The provided context from the document does no... \n", + "36 Based on the context provided, there is no exp... \n", + "37 Based on the provided context and general know... \n", + "38 Based on the provided context, here is the bac... \n", + "39 The species sR_IL6_sgp130, identified as mw633... \n", + "40 Based on the provided context, there is no spe... \n", + "41 Based on the provided context, there is no spe... \n", + "42 The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4... \n", + "43 The provided context does not contain direct i... " ] }, "execution_count": 6, @@ -269,13 +830,825 @@ "================================================================================\n", "1. IL6 (ID: mwf626e95e_543f_41e4_aad4_c6bf60ab345b)\n", "================================================================================\n", - "IL6, or Interleukin 6, is a cytokine that plays a significant role in the immune system. It is particularly important in the context of Crohn's disease, as it contributes to enhanced T-cell survival and apoptosis resistance in the lamina propria, along with increased chemokine secretion. IL-6 signaling occurs through two pathways: the classical pathway mediated by the membrane-bound IL-6 receptor (IL-6Rα) and the trans-signaling pathway mediated by the soluble IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of the gp130 coreceptor to form a receptor complex that initiates downstream signaling cascades.\n", + "The provided context outlines the biological function and role of IL-6, a cytokine important in the immune system. Based on the information:\n", + "\n", + "1. **Biological Function**:\n", + " IL-6 is a cytokine involved in immune regulation. It plays a crucial role in enhancing T-cell survival and resistance to apoptosis, particularly in the context of Crohn’s Disease, as well as in promoting chemokine secretion.\n", + "\n", + "2. **Role in Pathways**:\n", + " IL-6 signaling can proceed via two distinct pathways:\n", + " - The classical pathway, which involves the membrane-bound IL-6 receptor (IL-6Rα).\n", + " - The trans-signaling pathway, which involves a soluble IL-6 receptor (sIL-6Rα). In both pathways, IL-6 forms a complex with its respective receptor, which then recruits the gp130 coreceptor, leading to the formation of a hexameric receptor complex. This complex initiates phosphorylation of gp130-bound Janus kinase (Jak) proteins and subsequent activation of STAT3 (Signal Transducer and Activator of Transcription 3).\n", + "\n", + "3. **Interactions with Other Molecules**:\n", + " IL-6 interacts with its membrane-bound and soluble receptors to initiate signaling. The interaction sequence involves IL-6 binding to IL-6Rα, recruiting gp130, and activating downstream signaling molecules like Jak family proteins and STAT3.\n", + "\n", + "4. **Importance in the Biological System Being Modeled**:\n", + " IL-6 is highlighted as a significant contributor in the pathophysiology of Crohn’s Disease due to its roles in promoting immune cell activities that lead to inflammation. The ability of IL-6 to engage in both classical and trans-signaling pathways suggests it is a versatile mediator in inflammatory processes, making it a critical target for therapeutic interventions.\n", + "\n", + "5. **General Knowledge and Inference**:\n", + " Beyond the context, IL-6 is generally known to be involved in inflammation and is a key player in various inflammatory diseases. It is a target for drugs like tocilizumab, which inhibit IL-6 signaling by preventing the interaction of IL-6 with its receptor, thus being an important therapeutic strategy in diseases such as rheumatoid arthritis.\n", + "\n", + "In summary, IL-6 is a multifunctional cytokine central to immune regulation and inflammation, making it a crucial element in disease models, particularly those addressing inflammatory conditions like Crohn's Disease.\n", + "\n", + "================================================================================\n", + "2. sgp130 (ID: mwbbbce920_e8dd_4320_9386_fc94bfb2fc99)\n", + "================================================================================\n", + "Based on the context provided, sgp130 is a biological molecule that plays a role in inhibiting IL-6 trans-signaling. Here is a summary of its background information:\n", + "\n", + "1. **Biological Function**: sgp130 is derived from the extracellular portion of the gp130 protein. It serves to inhibit the signaling pathway of interleukin-6 (IL-6) by binding to the IL-6/sIL-6Rα complex, thereby preventing it from activating downstream signaling pathways. This inhibition is achieved by a fusion protein called sgp130Fc, which combines sgp130 with the Fc region of human IgG1.\n", + "\n", + "2. **Role in Pathways**: sgp130 influences the IL-6 signaling pathway, specifically targeting the trans-signaling aspect. IL-6 is a pro-inflammatory cytokine that can signal through a complex with soluble IL-6 receptor (sIL-6Rα) and gp130. By interfering with this pathway, sgp130 can modulate inflammatory responses.\n", + "\n", + "3. **Interactions with Other Molecules**: The primary interaction of sgp130 is with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 inhibits its ability to signal through the cell surface-bound gp130, thus blocking IL-6 mediated effects. The interaction between sgp130 and the IL-6/sIL-6Rα complex is central to its function.\n", + "\n", + "4. **Importance in the Biological System Being Modeled**: While sgp130 can effectively inhibit IL-6 trans-signaling, the context indicates that its role in the system being modeled is limited. The sensitivity analysis within the model shows that alterations in sgp130 levels have minimal effects on the steady-state values of output parameters due to the high baseline level of sgp130 compared to the relatively low concentration of free IL-6. This suggests that sgp130-based therapies may not be as impactful unless used at high and frequent doses. The model under discussion aimed at simulating its potential therapeutic use in conditions like Crohn’s disease.\n", + "\n", + "Overall, sgp130 is important for modulating IL-6 trans-signaling, but in the specific system modeled, its impact is limited under normal conditions due to its already high concentration compared to IL-6.\n", + "\n", + "================================================================================\n", + "3. sR_IL6_sgp130 (ID: mw810ff751_fa4e_4143_bd50_169b3e325e1e)\n", + "================================================================================\n", + "Based on the provided context from the document, 'sR_IL6_sgp130' seems to be a part of the IL-6 signaling pathway and is likely a reference to a complex involving soluble IL-6 receptor components. Here's a summary based on the information provided and general knowledge:\n", + "\n", + "- **Biological Function:** The complex is involved in modulating IL-6 signaling, particularly influencing the trans-signaling mechanism. Soluble gp130 (sgp130) acts as a natural inhibitor of IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing it from associating with membrane-bound gp130, which is necessary for signal transduction.\n", + "\n", + "- **Role in Pathways:** It is a critical modulator in the IL-6 signaling pathway. Normally, IL-6 binds to the soluble IL-6 receptor (sIL-6R), and this complex can further engage with gp130 on cell surfaces to propagate downstream signaling events. The sgp130 serves as a sink for these IL-6/sIL-6R complexes, limiting their ability to bind to cellular gp130 and hence reducing downstream signaling such as STAT3 activation.\n", + "\n", + "- **Interactions with Other Molecules:** The complex interacts primarily with IL-6 and its soluble receptor (sIL-6R). It prevents these molecules from engaging with cell-surface gp130, thus acting as a competitive inhibitor in the pathway.\n", + "\n", + "- **Importance in the Biological System:** In the context of the system being modeled, sgp130 is crucial as it regulates the balance of IL-6 signaling. Its high baseline concentration relative to IL-6 suggests it plays a stabilization role in keeping the system responsive only to significant changes in IL-6 levels. However, its effectiveness as a therapeutic agent, such as in Crohn’s disease, may require high and frequent dosing due to its large baseline presence and minimal effect on system dynamics under normal conditions.\n", + "\n", + "No direct information about 'sR_IL6_sgp130' as a separate distinct entity is found in the context, suggesting it might be inferred from understanding sgp130's complex with IL-6 and sIL-6R within the described signaling and therapeutic contexts.\n", + "\n", + "================================================================================\n", + "4. CRP (ID: mw114aa90f_5f5b_4fe8_9406_361c8489b6a1)\n", + "================================================================================\n", + "The term 'CRP' within the context provided refers to C-reactive protein, rather than a distinct biological species. C-reactive protein is a well-known biomarker present in the bloodstream, often used to assess inflammation within the body. Here's a summary of relevant background information about CRP based on the context and general biological understanding:\n", + "\n", + "- **Biological Function**: C-reactive protein is an acute-phase protein produced by the liver in response to inflammation. Its primary role is to bind to the surface of dead or dying cells (and some types of bacteria) to activate the complement system, thereby promoting phagocytosis by macrophages. This function is part of the body's innate immune response, aiding in clearing pathogens and dead cells from the bloodstream.\n", + "\n", + "- **Role in Pathways**: CRP is part of the body's acute-phase response to inflammation. Its levels in the blood increase rapidly in response to inflammatory cytokines, such as interleukin-6 (IL-6). This makes CRP an integral component in pathways related to the immune system's response to infection, injury, or chronic inflammatory diseases.\n", + "\n", + "- **Interactions with Other Molecules**: CRP interacts with the complement system components, particularly C1q, to initiate the complement cascade, a series of reactions that help eliminate pathogens. It also interacts with receptors on the surfaces of immune cells, such as Fcγ receptors, facilitating opsonization and phagocytosis. The document mentions interactions with IL-6 and its receptor IL-6Rα, as CRP production is highly influenced by IL-6 signaling.\n", + "\n", + "- **Importance in Biological Systems**: In the context of the model described, CRP is used as a biomarker to assess inflammation levels in patients, particularly those with conditions such as Crohn's disease. The model measures CRP levels to validate its predictions regarding drug effects on inflammatory pathways, highlighting its utility in monitoring disease activity and treatment efficacy.\n", + "\n", + "Overall, CRP is a crucial component in biological models focused on inflammatory diseases due to its rapid and measurable response to changes in underlying inflammation.\n", + "\n", + "================================================================================\n", + "5. sR (ID: mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc)\n", + "================================================================================\n", + "Based on the provided context, the species named 'sR' (ID: mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc) is likely related to the IL-6 signaling pathway. However, specific details about 'sR' are not provided directly in the context. Given that 'sR' is mentioned alongside IL-6, sIL-6R, and sgp130, it could be inferred that 'sR' is a component or modifier in the interleukin-6 (IL-6) signaling pathway.\n", + "\n", + "### Inferred Background Information\n", + "\n", + "**Biological Function**:\n", + "- It is probable that 'sR' is related to IL-6 signaling, potentially as a soluble receptor or co-receptor. Soluble receptors often exist as naturally occurring antagonists or helpers of cytokine signaling, modulating the pathway's activity.\n", + "\n", + "**Role in Pathways**:\n", + "- 'sR' might be involved in modulating the availability or activity of IL-6, similar to how sgp130 and sIL-6R work. sIL-6R is known to allow cells that do not possess membrane-bound IL-6R to respond to IL-6 through a process known as trans-signaling.\n", + "\n", + "**Interactions with Other Molecules**:\n", + "- It may interact with IL-6 or IL-6 receptor complexes. This interaction is crucial in the modulation of the pathway, likely affecting the downstream signaling events such as the activation of STAT3 (Signal Transducer and Activator of Transcription 3).\n", + "\n", + "**Importance in the Biological System**:\n", + "- Given its potential role in cytokine signaling, 'sR' would be important in regulating inflammatory responses, immune system signaling, and possibly in the pathophysiology of diseases where IL-6 is a key player, such as autoimmune diseases.\n", + "\n", + "### Contextual Consideration\n", + "- The provided context includes a discussion on sensitivity analysis and the role of sgp130 with IL-6, which highlights the intricate balance within the cytokine signaling pathways. Though 'sR' is not explicitly expanded upon, understanding the dynamics of similar molecules like sIL-6R and sgp130 offers insights into its potential biological significance.\n", + " \n", + "This inferred information aligns with typical roles of soluble cytokine receptors in biological systems. However, the exact nature and function of 'sR' would require further specific details or experimental data.\n", + "\n", + "================================================================================\n", + "6. sR_IL6 (ID: mw03db56ac_8dc6_4931_ae82_fef706d2ee3d)\n", + "================================================================================\n", + "The species labeled 'sR_IL6' in the context provided appears to refer to a soluble receptor for interleukin-6 (IL-6), often denoted as sIL-6R. Soluble IL-6 receptors play a crucial role in IL-6 trans-signaling pathways, which differ from classical signaling by involving the soluble receptor form (sIL-6R) rather than the membrane-bound IL-6 receptor (IL-6R).\n", + "\n", + "### Biological Function:\n", + "- **Soluble IL-6 Receptor (sIL-6R):** Its primary function is to bind to the cytokine IL-6, forming a complex that can activate cells that do not have membrane-bound IL-6 receptors. This process is known as \"trans-signaling\" and allows for a wider range of cells to respond to IL-6, expanding its biological effects.\n", + "\n", + "### Role in Pathways:\n", + "- **Trans-signaling Pathway:** In trans-signaling, the IL-6/sIL-6R complex associates with the membrane protein gp130, facilitating intracellular signaling cascades such as the JAK/STAT pathway. This activation leads to gene transcription and biological responses in target cells.\n", + "- **Classical Signaling Pathway:** sIL-6R is involved in sequestering IL-6 in the presence of the regulatory protein sgp130, modulating the signaling capacity by preventing excessive inflammatory signaling.\n", + "\n", + "### Interactions with Other Molecules:\n", + "- **IL-6:** The soluble receptor interacts with IL-6 to initiate trans-signaling.\n", + "- **gp130:** Binds the IL-6/sIL-6R complex, essential for downstream signal transduction.\n", + "- **sgp130:** Acts as a natural inhibitor by sequestering IL-6/sIL-6R complexes, dampening potential overactivation of IL-6 signaling.\n", + "\n", + "### Importance in the Biological System:\n", + "In the context of Crohn's disease and immune regulation, the IL-6/sIL-6R complex plays a critical role. Modulating this pathway can influence disease progression and therapeutic outcomes. Targeting the IL-6/sIL-6R complex could offer promising treatments by adjusting the immune response and inflammation characteristic of the condition.\n", + "\n", + "The context suggests that sIL-6R could be involved in a model for chronic inflammatory conditions, highlighting its significance in promoting or inhibiting inflammation through different signaling pathways. By understanding its interactions and functions, potential strategies can be developed for therapeutic interventions, such as using antibodies to modify its activity.\n", + "\n", + "================================================================================\n", + "7. Ab (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded)\n", + "================================================================================\n", + "Based on the provided documents, there isn't direct and specific information regarding the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded) in the given context. However, based on general knowledge and context clues, 'Ab' likely refers to an antibody, given the reference to serum Ab concentrations and interaction with IL-6 and sIL-6Rα complexes.\n", + "\n", + "1. **Biological Function**: Antibodies (Ab) are proteins produced by the immune system that recognize and bind to specific antigens, such as pathogens (viruses, bacteria) or other target molecules. Their primary function is to neutralize these antigens and facilitate their destruction by other immune cells.\n", + "\n", + "2. **Role in Pathways**: In the context provided, 'Ab' is involved in targeting the IL-6 and IL-6Rα pathways. This is indicative of its role in modulating inflammatory responses, likely through the inhibition of the IL-6 signaling pathway.\n", + "\n", + "3. **Interactions with Other Molecules**: The document mentions the anti-IL-6 Ab dose response and its effects on serum CRP suppression. The interaction specifically involves the binding of the antibody to IL-6 and the IL-6/sIL-6Rα complex, which suggests its use in blocking or reducing the inflammatory signaling mediated by these molecules.\n", + "\n", + "4. **Importance in the Biological System**: The blocking or modulation of IL-6 signaling by antibodies plays a significant role in managing inflammatory diseases. The context implies that targeting IL-6 and its receptor complexes can be part of a therapeutic strategy for conditions characterized by excessive inflammation, such as inflammatory bowel diseases.\n", + "\n", + "Given these points, 'Ab' in this context seems to be associated with therapeutic antibodies used to manage inflammation by interfering with specific cytokine pathways, particularly involving IL-6. This type of intervention is crucial in diseases where cytokine signaling contributes to the pathology.\n", + "\n", + "================================================================================\n", + "8. Ab_sR (ID: mw1da111f2_a036_4392_8512_015005bdcbb7)\n", + "================================================================================\n", + "The specific species 'Ab_sR' (ID: mw1da111f2_a036_4392_8512_015005bdcbb7) located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e does not seem to be explicitly mentioned in the provided context. However, based on the context and general knowledge, we can infer some relevant background information about similar biological components that usually appear in such contexts. \n", + "\n", + "The context mentions components such as sIL-6R, IL-6, and their interactions, which are indicative of a role in inflammatory response pathways. sIL-6R is a soluble form of the IL-6 receptor, and it typically participates in what's known as IL-6 trans-signaling. In this process, instead of the membrane-bound receptor, IL-6 binds to sIL-6R to form a complex that can interact with the gp130 protein, initiating signaling cascades even in cells that do not express the full receptor. This mechanism is important in regulating immune responses, inflammation, and possibly chronic inflammatory diseases by influencing the production of acute-phase proteins like C-reactive protein (CRP).\n", + "\n", + "Given this understanding, 'Ab_sR' could potentially refer to an antibody or an interaction factor related to the soluble receptor pathways, possibly playing a regulatory or inhibitory role in these pathways through binding interactions. Its importance might then be deduced from its capability to modulate these signaling pathways, with potential therapeutic implications for diseases driven by excessive IL-6 signaling.\n", + "\n", + "If Ab_sR is an antibody, it could play a role similar to antibodies against IL-6 or IL-6Rα, aiming to disrupt or modify these signaling pathways, potentially reducing inflammatory responses as a therapeutic strategy. Such antibodies are being explored in contexts of autoimmune diseases, cancers, and inflammatory disorders. \n", + "\n", + "Note: This inference is made based on the context provided and common biological functions of related components. Further specific information would be required for more accurate detailing of Ab_sR's role.\n", + "\n", + "================================================================================\n", + "9. Ab_sR_IL6 (ID: mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac)\n", + "================================================================================\n", + "The context provided does not directly specify information about a species named 'Ab_sR_IL6'. However, based on general knowledge and the context given, we can make some inferences and provide related information:\n", + "\n", + "1. **Biological Function**: Given the naming convention used ('Ab_sR_IL6'), it is likely that this refers to an antibody (Ab) targeting a soluble receptor (sR) for interleukin-6 (IL-6), possibly inhibiting its action. IL-6 is a cytokine involved in inflammatory and immune responses.\n", + "\n", + "2. **Role in Pathways**: IL-6 typically signals through its receptor complex, including IL-6R and gp130, to activate downstream signaling pathways like JAK/STAT, leading to the activation of transcription factors such as STAT3. This cascade leads to the expression of various genes involved in inflammation and immune regulation.\n", + "\n", + "3. **Interactions with Other Molecules**: Based on the context, the antibody could be interacting with the IL-6/sIL-6R complex to modulate its effects. The text describes interactions involving sIL-6R and IL-6, potentially including competition or inhibition by antibodies that alter the signaling outcomes and inflammatory responses.\n", + "\n", + "4. **Importance in the Biological System Being Modeled**: In the context of the model described, inhibiting the IL-6/sIL-6R interaction is a focus, likely due to its role in conditions like Crohn's Disease or rheumatoid arthritis. Modifying this pathway's activity through an antibody such as 'Ab_sR_IL6' might be of therapeutic significance, potentially helping to suppress excessive inflammatory responses, as suggested by the interest in CRP (C-reactive protein) suppression and dose-response relationships.\n", + "\n", + "In summary, 'Ab_sR_IL6' is likely conceptualized as an antibody targeting the soluble IL-6 receptor to interfere with IL-6 mediated signaling pathways, which are pivotal in certain inflammatory diseases. While specific details are not provided in the context, this inference aligns with common therapeutic strategies involving cytokine signaling modulation.\n", + "\n", + "================================================================================\n", + "10. CRP Suppression (%) (ID: CRP_Suppression___)\n", + "================================================================================\n", + "Based on the context provided, \"CRP Suppression (%)\" refers to the measurement of the reduction in serum C-reactive protein (CRP) levels. CRP is a biological marker of inflammation, and its levels can be indicative of inflammatory responses in the body. Understanding the suppression of CRP levels has the following implications:\n", + "\n", + "1. **Biological Function**: CRP is an acute phase protein, produced by the liver in response to inflammation. It plays a role in the body's immune response, indicating tissue damage or inflammation.\n", + "\n", + "2. **Role in Pathways**: CRP is involved in the inflammatory pathway. Suppressing CRP levels typically suggests an underlying modulation of the inflammatory response, often facilitated through interventions like antibodies targeting specific inflammatory cytokines or receptors, such as IL-6 or IL-6Rα in this context.\n", + "\n", + "3. **Interactions with Other Molecules**: The context implies interactions with Interleukin-6 (IL-6) and its receptor (IL-6Rα). Treatments with anti–IL-6 or anti–IL-6Rα antibodies reduce CRP levels, thereby modulating inflammation, as indicated by the provided data on drug dose and CRP suppression.\n", + "\n", + "4. **Importance in the Biological System**: Suppression of serum CRP is an important indicator of the efficacy of drugs, like anti-IL-6 or anti-IL-6Rα antibodies, in reducing inflammatory responses. This makes CRP suppression a critical measure for evaluating the outcome of therapeutic interventions aimed at inflammatory diseases.\n", + "\n", + "While the context does not directly describe CRP Suppression (%) as a biological species, it is a measure of the effectiveness of treatments targeting inflammatory pathways. Interactions that lead to its suppression are essential for understanding therapeutic impacts on inflammation-related conditions.\n", + "\n", + "================================================================================\n", + "11. CRP (% of baseline) (ID: CRP____of_baseline)\n", + "================================================================================\n", + "The term \"CRP (% of baseline)\" is referring to C-reactive protein (CRP) levels measured as a percentage of a baseline value. In the context provided, it appears to be a metric used in the modeling and analysis of clinical trial data related to anti–IL-6Rα antibody treatments, specifically tocilizumab, which is an anti-inflammatory medication. Here's a summary based on the context and general knowledge about CRP:\n", + "\n", + "1. **Biological Function:**\n", + " - CRP is a protein produced by the liver in response to inflammation. It is part of the acute phase response to inflammation and is a biomarker commonly used to assess inflammation and tissue injury.\n", + "\n", + "2. **Role in Pathways:**\n", + " - CRP is a key player in the acute inflammatory response and is involved in pathways that react to injury, infection, and inflammation. It interacts with the immune system to facilitate the clearance of necrotic and apoptotic cells and bacteria.\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " - CRP levels are influenced by the presence of pro-inflammatory cytokines, particularly interleukin-6 (IL-6). This context highlights the interaction between CRP levels and anti–IL-6Rα antibodies, which inhibit IL-6 signaling and therefore can suppress CRP production as part of their therapeutic action.\n", + "\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - In the given context, CRP (% of baseline) serves as an important biomarker for evaluating the efficacy of tocilizumab treatment in suppressing inflammation. The model uses CRP levels to compare and validate simulation results against clinical trial data, indicating its critical role in assessing treatment impacts.\n", + "\n", + "No specific unique details beyond this general framework are detailed in the context, but from a systems biology perspective, CRP measurement is significant for understanding inflammatory processes and the body's response to therapeutic interventions.\n", + "\n", + "================================================================================\n", + "12. gp130 (ID: mw80848184_e2dd_47ce_86d7_7a21479342bd)\n", + "================================================================================\n", + "The species named 'gp130' refers to a protein that plays a significant role in the signaling pathway involving interleukin-6 (IL-6) and its receptor. \n", + "\n", + "### Biological Function:\n", + "- **gp130 is a Signal Transducer**: It is primarily a signal-transducing component of the IL-6 receptor complex. It does not bind IL-6 by itself but acts as a signal transducer when associated with IL-6 and IL-6 receptor (IL-6R).\n", + "\n", + "### Role in Pathways:\n", + "- **Interaction with IL-6/IL-6R**: gp130 is crucial in the formation of the signaling complex with IL-6 and its soluble receptor sIL-6R. This complex is central to IL-6 signaling pathways.\n", + "- **Inhibition of IL-6 Trans-Signaling**: A fusion protein known as sgp130Fc, which combines the extracellular portion of gp130 with an Fc region, has been shown to inhibit IL-6 trans-signaling, demonstrating gp130’s role in regulatory mechanisms.\n", + "\n", + "### Interactions with Other Molecules:\n", + "- **Complex Formation**: It forms a complex with IL-6 and IL-6R, contributing to signal transduction.\n", + "- **Natural Inhibitor**: Soluble gp130 (sgp130) serves as a natural inhibitor of the IL-6/sIL-6R signaling pathway, preventing excessive signal transduction.\n", + "\n", + "### Importance in the Biological System:\n", + "- **Regulatory Role**: The high baseline level of soluble gp130 (sgp130) in the system acts as a buffering agent against changes in the levels of IL-6/sIL-6R complex, highlighting its regulatory importance.\n", + "- **Therapeutic Potential**: Therapeutic approaches using sgp130 to target IL-6 signaling pathways, such as in the treatment of Crohn’s disease, underscore its clinical significance.\n", + " \n", + "Given these roles, gp130 is a critical component in the IL-6 signaling pathway and has potential therapeutic implications due to its regulatory capacities in controlling inflammatory responses.\n", + "\n", + "================================================================================\n", + "13. R_IL6_gp130 (ID: mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a)\n", + "================================================================================\n", + "The species named 'R_IL6_gp130', based on its naming and the context provided, likely refers to a complex or interaction involving the cytokine interleukin-6 (IL-6) and the signal transducer glycoprotein 130 (gp130). While the specific document does not provide detailed information about R_IL6_gp130, general knowledge about the IL-6/gp130 interaction helps us understand its potential biological significance.\n", + "\n", + "### Biological Function:\n", + "- **IL-6:** It is a cytokine involved in the regulation of immune responses, inflammation, and hematopoiesis. It plays a crucial role in acute phase responses and is produced at sites of inflammation.\n", + "- **gp130:** It serves as a signal transducer in the cytokine receptor complex, particularly for the IL-6 family of cytokines. It is involved in several cellular processes, including cell growth and differentiation.\n", + "\n", + "### Role in Pathways:\n", + "- The IL-6/gp130 interaction is central to both classical and trans-signaling pathways. In classical signaling, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), which then associates with gp130 to initiate downstream signaling.\n", + "- In trans-signaling, IL-6 binds to a soluble form of the IL-6 receptor (sIL-6R), and this complex can then associate with gp130 on the target cell surface, allowing cells that do not express membrane-bound IL-6R to respond to IL-6.\n", + "\n", + "### Interactions with Other Molecules:\n", + "- gp130 is a common subunit shared by several cytokine receptors in the IL-6 family, meaning it participates in a variety of signaling complexes.\n", + "- The soluble form of gp130 (sgp130) can act as a natural inhibitor by binding to IL-6/sIL-6R complexes and preventing them from interacting with membrane-bound gp130.\n", + "\n", + "### Importance in the Biological System Being Modeled:\n", + "- Given the context of inflammatory diseases such as Crohn’s disease, the IL-6/gp130 axis is likely a critical component in the inflammatory response modulation.\n", + "- The application of sgp130, or its fusion forms like sgp130Fc, demonstrates the pathway's therapeutic significance as a target for damping excessive IL-6-mediated signaling in inflammatory diseases.\n", + "\n", + "In summary, R_IL6_gp130 refers to a key interaction in the IL-6 signaling pathway, emphasizing its role in inflammatory responses and its potential as a therapeutic target in autoimmune diseases like Crohn's.\n", + "\n", + "================================================================================\n", + "14. sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw4638f126_8cb8_4021_ab41_6ae195743ba0)\n", + "================================================================================\n", + "Based on the provided context and general knowledge, here is the background information on the species 'sR_IL6' with the identifier 'mw4638f126_8cb8_4021_ab41_6ae195743ba0', situated within 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e':\n", + "\n", + "1. **Biological Function**: 'sR_IL6' likely refers to the soluble receptor for Interleukin-6 (sIL-6R). Soluble receptors such as sIL-6R can bind to the cytokine IL-6, acting as a co-receptor that allows IL-6 to engage in signaling pathways even in cells that do not express the membrane-bound IL-6 receptor.\n", + "\n", + "2. **Role in Pathways**: In the immune system, IL-6 can signal through two main pathways:\n", + " - **Classical signaling**: IL-6 binds to membrane-bound IL-6R and recruits the gp130 protein to initiate downstream signaling.\n", + " - **Trans-signaling**: sIL-6R, in complex with IL-6, engages gp130 on cells that do not have the IL-6 receptor, thus expanding the range of cells that can respond to IL-6. This is particularly relevant in inflammatory responses and is studied in contexts such as Crohn's disease.\n", + "\n", + "3. **Interactions with Other Molecules**: \n", + " - sIL-6R forms a complex with IL-6 which can then bind to gp130, leading to activation of downstream signaling pathways such as the JAK/STAT pathway.\n", + " - sIL-6R can be sequestered by sgp130, a soluble form of gp130, which can regulate the availability of the IL-6/sIL-6R complex for signaling.\n", + " - C-reactive protein (CRP) is involved in the production of sIL-6R through a process known as CRP-mediated shedding.\n", + "\n", + "4. **Importance in the Biological System**: \n", + " - sIL-6R plays a crucial role in mediating IL-6 trans-signaling, particularly in contexts like chronic inflammation and autoimmune diseases such as Crohn's disease.\n", + " - The presence of sIL-6R enables IL-6 to exert its effects even in cells lacking direct IL-6 receptors, thereby widening its scope of action within the immune regulatory processes.\n", + " - Understanding the dynamics of sIL-6R in combination with IL-6 is important for therapeutic considerations, as targeting these complexes can influence pharmacological outcomes in disease states.\n", + "\n", + "Thus, sR_IL6 (inferred as sIL-6R) is integral to the IL-6 signaling pathways, facilitating broad immunological responses through its role in trans-signaling and interaction with IL-6 and other molecular regulators like sgp130.\n", + "\n", + "================================================================================\n", + "15. R (ID: mw10315fa3_6f13_4618_bda8_a8694bd3c374)\n", + "================================================================================\n", + "Given the context provided, the information about the species named 'R' (ID: mw10315fa3_6f13_4618_bda8_a8694bd3c374) is not directly mentioned in the documents. However, we can make inferences based on the information about related molecules and pathways described in the context, particularly those involving IL-6 (interleukin-6) and its receptor.\n", + "\n", + "### Inferred Background Information about 'R':\n", + "\n", + "1. **Biological Function**:\n", + " - Since the context discusses IL-6 and its receptors (sIL-6R and IL-6Rα), 'R' could potentially be related to components in the IL-6 signaling pathway. IL-6 is a cytokine involved in inflammation and immune response regulation.\n", + "\n", + "2. **Role in Pathways**:\n", + " - IL-6 interacts with both membrane-bound and soluble forms of its receptor (IL-6R) to initiate downstream signaling cascades, such as the JAK/STAT pathway, which leads to the activation of transcription factors like STAT3 (signal transducer and activator of transcription 3).\n", + " - The pathway is involved in the transcription of various genes, including those coding for acute-phase proteins like CRP (C-reactive protein), indicating a role in inflammatory processes and liver function.\n", + "\n", + "3. **Interactions with Other Molecules**:\n", + " - IL-6, in combination with its receptor, can activate a signaling complex that involves the JAK proteins and STAT3, influencing gene expression. Soluble forms of the receptor, such as sIL-6R, play a role in trans-signaling, which can modulate responses in cells that do not express the membrane-bound receptor.\n", + "\n", + "4. **Importance in the Biological System**:\n", + " - Given that IL-6 signaling impacts acute-phase response and immune regulation, molecules within this pathway, including 'R' if it is part of this system, are crucial for modulating inflammatory responses. They may be targeted in therapeutic contexts, such as with anti–IL-6 or anti–IL-6Rα therapies, which are indicated in the documents as treatments influencing biomarkers like CRP.\n", + "\n", + "In conclusion, without specific data directly linked to 'R', it can be inferred that 'R' is potentially part of the IL-6 pathway components, involved in immune and inflammatory responses, and plays a significant role in cellular signaling and communication within this biological system.\n", + "\n", + "================================================================================\n", + "16. IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1)\n", + "================================================================================\n", + "Based on the context provided, the species referred to as 'IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is likely Interleukin-6 (IL-6), a cytokine involved in various biological processes. Here is a summary of relevant background information about IL-6:\n", + "\n", + "1. **Biological Function:**\n", + " - IL-6 is a cytokine that plays a crucial role in immune regulation. It is involved in the inflammatory response and is essential for the body's defense against infections and injuries.\n", + "\n", + "2. **Role in Pathways:**\n", + " - IL-6 signaling can occur through two main pathways:\n", + " - **Classical Pathway:** This involves the membrane-bound IL-6 receptor (IL-6Rα) where IL-6 binds to IL-6Rα, forming a complex that recruits a membrane-bound gp130 coreceptor, triggering downstream signaling cascades.\n", + " - **Trans-signaling Pathway:** This involves the soluble IL-6 receptor (sIL-6Rα). The IL-6/sIL-6Rα complex can associate with gp130 to initiate signaling in cells that do not express the membrane-bound IL-6Rα. This pathway is particularly important in inflammatory diseases.\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " - IL-6 interacts with IL-6Rα and gp130 to form a receptor complex that activates intracellular signaling pathways.\n", + " - It leads to the phosphorylation of Janus kinase (Jak) family proteins and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3), which are critical for transmitting the signal inside the cell.\n", + "\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - In the context of Crohn's disease, IL-6 contributes to enhanced T-cell survival and resistance to apoptosis in the lamina propria, along with elevated chemokine secretion. This makes it a significant player in the disease's pathology.\n", + " - The study of IL-6 and its pathways is crucial in understanding its role in diseases such as Crohn's disease and rheumatoid arthritis, and in developing therapeutic interventions targeting IL-6 signaling.\n", + "\n", + "Overall, IL-6 is an important cytokine with significant roles in immune response and inflammation, making it a key target for research in immune-mediated diseases.\n", + "\n", + "================================================================================\n", + "17. R_IL6 (ID: mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83)\n", + "================================================================================\n", + "Based on the context provided, there is no specific mention of a species named 'R_IL6'. However, based on the context and related molecules mentioned, it is possible to infer some insights into what 'R_IL6' might relate to.\n", + "\n", + "### Biological Function:\n", + "- **IL-6:** IL-6 (Interleukin-6) is a cytokine involved in immune response, inflammation, and hematopoiesis. It plays a significant role in the body's defense mechanisms and is implicated in various diseases when dysregulated.\n", + "\n", + "### Role in Pathways:\n", + "- **IL-6 Signaling Pathway:** This pathway involves the binding of IL-6 to its receptor, IL-6R, and generally leads to the activation of JAK/STAT signaling pathways. This signaling can induce transcription and various immune responses.\n", + "\n", + "### Interactions with Other Molecules:\n", + "- **IL-6R and sIL-6R (soluble IL-6 receptor):** The IL-6 signaling requires the complex formation of IL-6 with its receptor IL-6R, including its soluble form sIL-6R. This complex can further bind to another molecule, gp130 (glycoprotein 130), which is necessary for signal transduction.\n", + "- **STAT3:** The context mentions pSTAT3 signaling, indicating that IL-6 signaling involves phosphorylation of STAT3, a transcription factor that mediates various gene expressions in response to IL-6.\n", + "\n", + "### Importance in the Biological System Being Modeled:\n", + "- **Regulation and Modeling:** IL-6 is involved in the regulation of immune processes, and its signaling is crucial in understanding conditions like Crohn's disease or rheumatoid arthritis. The context mentions modeling efforts and pharmacokinetic analyses suggesting a focus on IL-6 and its receptor interactions.\n", + "- **Treatment Implications:** The modeling discussed, such as the dose-response characteristics, indicates IL-6's importance in therapeutic frameworks, potentially focusing on disorders with immune dysregulation.\n", + "\n", + "### Potential Inference for 'R_IL6':\n", + "- While there is no direct mention of 'R_IL6', it could potentially refer to a variant, receptor, or complex of IL-6 involved in signaling pathways. It might be modeled similarly in studies related to immune regulation or therapeutic targeting. Given the context, it is likely associated with IL-6's complex pathways and interactions within the immune system.\n", + "\n", + "In summary, 'R_IL6' could be a component related to IL-6 signaling, likely significant in immune system modeling and therapeutic interventions.\n", + "\n", + "================================================================================\n", + "18. Ractive (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb)\n", + "================================================================================\n", + "The context provided does not include specific information about a species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). However, I can provide inferential information based on the general context described, which involves IL-6 signaling and therapeutic interventions in conditions like rheumatoid arthritis and Crohn’s disease.\n", + "\n", + "1. **Biological Function:**\n", + " - Although 'Ractive' is not directly mentioned, within the context of an immune regulation framework, it could be hypothesized that 'Ractive' might represent a molecule involved in the immune response or signal transduction, perhaps similar to interleukins or receptors.\n", + "\n", + "2. **Role in Pathways:**\n", + " - Considering the IL-6 signaling pathway is a focal point of the study, 'Ractive' might play a role similar to elements of the IL-6 signaling cascade. This could involve participation in cytokine signaling or acting as a receptor or receptor complex, similar to IL-6 or its soluble receptor counterparts.\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " - 'Ractive' might engage in interactions akin to the IL-6 and its soluble receptor interactions. Such molecules often form complexes that could be potential targets for therapeutic antibodies or other modulators, a common approach in autoimmune conditions like those discussed.\n", + "\n", + "4. **Importance in the Biological System:**\n", + " - If 'Ractive' partakes in a pathway analogous to IL-6 signaling, it could be crucial in mediating inflammatory responses, playing a part in disease progression or resolution, and thus presenting itself as a possible target for therapeutic intervention.\n", + "\n", + "Without specific information on 'Ractive' from the text, these interpretations are speculative and should be considered within the broader context of known signaling pathways and therapeutic targets discussed in the study.\n", + "\n", + "================================================================================\n", + "19. STAT3 (ID: mw42054cd7_17af_46da_970c_7f99151906ad)\n", + "================================================================================\n", + "Based on the provided context and general knowledge:\n", + "\n", + "### Biological Function of STAT3\n", + "STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor activated by phosphorylation. It is a key player in transmitting signals from various cytokines and growth factors to the cell nucleus, where it modifies gene expression. STAT3 is critical for regulating numerous biological processes, including cell growth, apoptosis, and immune response.\n", + "\n", + "### Role in Pathways\n", + "STAT3 is involved in the JAK-STAT signaling pathway. Upon activation, typically by cytokines such as IL-6, STAT3 is phosphorylated by associated Janus kinases (JAKs), dimerizes, and translocates to the nucleus. In this context, STAT3 appears integral to the IL-6 signaling pathway, which is involved in various cellular responses, including inflammation, immune function, and acute-phase reactions.\n", + "\n", + "### Interactions with Other Molecules\n", + "Within the IL-6 signaling pathway, STAT3 interacts with molecules such as the IL-6 receptor (IL-6R), gp130, and soluble forms of these receptors (sIL-6R and sgp130). The phosphorylation of STAT3 (pSTAT3) indicates its activation and subsequent transcriptional regulation of target genes.\n", + "\n", + "### Importance in Biological Systems\n", + "STAT3 plays a significant role in mediating the effects of cytokines like IL-6, which are crucial in immune responses and inflammation. The context mentions disease models such as Crohn's disease, where increased activation of STAT3 (pSTAT3) in tissues is noted, highlighting its potential role in the disease's inflammatory processes. This suggests that STAT3's regulation is pivotal in understanding and developing therapeutic approaches for immune and inflammatory disorders.\n", + "\n", + "In summary, STAT3 is a central molecule in cytokine signaling pathways that influence immune function and inflammation, making it a critical target for studying diseases characterized by dysregulated immune responses, such as Crohn's disease.\n", + "\n", + "================================================================================\n", + "20. pSTAT3 (ID: mw39c2e431_fdc3_4964_be29_6ca856620b1b)\n", + "================================================================================\n", + "The context provided mainly revolves around the IL-6 signaling pathway and its components, such as IL-6Rα, gp130, sIL-6Rα, sgp130, and CRP, with sporadic mentions of STAT3 and pSTAT3. Here’s a summary focused on pSTAT3 based on the document and broader biological knowledge:\n", + "\n", + "### pSTAT3 Biological Function\n", + "- **pSTAT3** refers to the phosphorylated form of STAT3 (Signal Transducer and Activator of Transcription 3).\n", + "- STAT3 is a transcription factor activated in response to cytokines like IL-6.\n", + "- When phosphorylated, STAT3 dimerizes and translocates to the nucleus to regulate the expression of target genes.\n", + "\n", + "### Role in Pathways\n", + "- **IL-6 Signaling**: pSTAT3 is a critical component of the IL-6 signaling pathway. The binding of IL-6 to its receptor leads to the activation of the JAK kinases, which in turn phosphorylate STAT3.\n", + "- **Gene Expression**: pSTAT3 influences the transcription of various genes involved in immune responses, cell survival, and proliferation.\n", + "\n", + "### Interactions with Other Molecules\n", + "- **IL-6 and sIL-6Rα**: The context describes the significance of trans-signaling mediated by IL-6 and its soluble receptor forms, which lead to STAT3 phosphorylation.\n", + "- **gp130**: This coreceptor is crucial for the activation of STAT3. It binds the IL-6/sIL-6R complex leading to STAT3 phosphorylation.\n", + "- **CRP and other gene products**: The activation of STAT3 can influence the expression of C-reactive protein and other acute-phase proteins.\n", + "\n", + "### Importance in the Biological System\n", + "- **Pathological Conditions**: The document mentions increased pSTAT3 levels in colon biopsies in the context of Crohn’s disease, suggesting its role in inflammatory bowel diseases.\n", + "- **Biological Significance**: Being a part of the IL-6 signaling pathway, pSTAT3 is important in mediating immune responses and might have implications in various diseases due to dysregulated cytokine signaling.\n", + "\n", + "In summary, pSTAT3 is a pivotal signaling molecule involved in transcriptional regulation, primarily within the IL-6-mediated pathway. Its phosphorylation status determines its activity, which can impact various biological processes and contributes to disease states such as inflammatory bowel disease.\n", + "\n", + "================================================================================\n", + "21. CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mwd5313618_89eb_4c8c_bc82_66f10f966349)\n", + "================================================================================\n", + "The species referred to as \"CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\" in the provided context likely represents C-reactive protein (CRP), based on the common abbreviation for C-reactive protein. Here is a summary of the relevant background information regarding CRP:\n", + "\n", + "1. **Biological Function:**\n", + " - CRP is an acute-phase protein produced by the liver in response to inflammation. Its primary function is to bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system via C1q.\n", + "\n", + "2. **Role in Pathways:**\n", + " - CRP is often used as a clinical biomarker for inflammation. It plays a significant role in the pathway of immune response, particularly in recognizing and promoting the clearance of pathogens and damaged cells, thereby serving as a marker of inflammation and immune system activation.\n", + " - In the context of the simulation model discussed, changes in CRP levels can indicate the effectiveness of drug treatments targeting the IL-6 signaling pathway, as CRP levels are a downstream effect of cytokine signaling, particularly IL-6.\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " - CRP interacts with various components of the immune system such as the complement system. It works closely with interleukin-6 (IL-6), as IL-6 is a major inducer of CRP synthesis in the liver.\n", + " - The context mentions interactions with drugs such as anti-IL-6Rα antibodies, which suggests that CRP levels are used to measure the impact of these treatments on inflammation levels in diseases like Crohn's disease.\n", + "\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - Within the modeled system (as described in the context), CRP serves as a critical marker for inflammation, allowing researchers to predict the impact of various treatment strategies on inflammatory diseases like Crohn's disease.\n", + " - The model’s ability to predict changes in CRP levels helps in studying the effects of perturbations through different therapeutic approaches aimed at inhibiting the IL-6 signaling pathway.\n", + "\n", + "Overall, CRP is an important indicator of inflammation and is crucial in the validation and assessment of disease models involving inflammatory processes, such as those involving IL-6 signaling.\n", + "\n", + "================================================================================\n", + "22. sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw2e464cf3_a09c_4b7c_9f3c_06720016a48e)\n", + "================================================================================\n", + "Based on the provided context, specific information about the species 'sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned. However, inferring from the general context of the documents, which involve molecular interactions and pathways related to the IL-6 signaling system, the following insights can be suggested:\n", + "\n", + "1. **Biological Function**:\n", + " - The 'sR' component is likely a part of the IL-6 signaling pathway. In similar contexts, 'sR' often denotes soluble receptors. Soluble receptors can modulate the activity of their respective cytokines or hormones by binding to them and altering their bioavailability or impacting downstream signaling pathways.\n", + "\n", + "2. **Role in Pathways**:\n", + " - Considering the IL-6 pathway is mentioned, the 'sR' species might function in the classical signaling or trans-signaling pathways of IL-6. In these pathways, soluble receptors either enhance or inhibit signal transduction, impacting gene expression mediated by factors like STAT3.\n", + "\n", + "3. **Interactions with Other Molecules**:\n", + " - The context suggests interaction with the IL-6 cytokine, as soluble IL-6 receptors (e.g., sIL-6R) bind IL-6, forming a complex (IL-6:sR) that may interact with other receptor components, such as gp130, to elicit a cellular response. These interactions are crucial for regulating inflammatory responses and immune function.\n", + "\n", + "4. **Importance in the Biological System Being Modeled**:\n", + " - Soluble receptors are significant in maintaining homeostasis and regulating the intensity of cytokine signaling. The modeling aspect suggests that understanding the dynamic balance of these components (like sgp130, mentioned in the document) is crucial for accurately predicting system behavior under various conditions and treatments, especially targeting IL-6 or its receptors.\n", + "\n", + "In summary, 'sR' in this context is likely a soluble receptor involved in the IL-6 signaling pathway, influencing immune responses by modulating cytokine availability and activity.\n", + "\n", + "================================================================================\n", + "23. CRPExtracellular (ID: mw36ea78c1_ed71_4def_96d3_857a442d7195)\n", + "================================================================================\n", + "The species named 'CRPExtracellular' likely refers to the extracellular form of C-reactive protein (CRP), a well-known biomarker and acute-phase protein in various biological systems, particularly in the context of inflammation.\n", + "\n", + "### Biological Function\n", + "C-reactive protein (CRP) is produced by the liver in response to inflammation. It is an acute-phase protein that plays a critical role in the host's defense mechanism. CRP is part of the innate immune system as it binds to the surface of dead or dying cells and certain bacteria to activate the complement system, promoting phagocytosis by macrophages.\n", + "\n", + "### Role in Pathways\n", + "In the context of the provided documents, CRP is linked to the IL-6 signaling pathway. IL-6 is a cytokine that stimulates the production of CRP in the liver. The IL-6 mediated pathway contributes to inflammatory responses, and CRP serves as a downstream marker for inflammation. The model mentioned explores strategies to treat Crohn's disease by inhibiting IL-6 signaling, which suggests a modulation of CRP levels.\n", + "\n", + "### Interactions with Other Molecules\n", + "CRP interacts with various molecules and systems in the body:\n", + "- It binds to phosphocholine on the surface of dead cells and some types of bacteria.\n", + "- CRP activates the complement system, which enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells.\n", + "- CRP levels are used to assess the extent of inflammation in response to stimuli like IL-6, another cytokine involved in the body's inflammatory response.\n", + "\n", + "### Importance in the Biological System Being Modeled\n", + "In the biological model presented in the documents, CRP serves as a critical biomarker to evaluate the efficacy of therapeutic strategies targeting IL-6 signaling in inflammatory diseases like Crohn's disease. The documents emphasize the model's capacity to predict the response of CRP levels to different treatment strategies, validating the trained model against clinical trial data. Suppression of CRP is an indicator of effective inhibition of inflammation, showcasing the importance of CRP measurement in assessing the success of interventions aimed at controlling inflammatory pathways.\n", + "\n", + "In summary, CRPExtracellular represents the extracellular C-reactive protein operating as a biomarker for inflammation, influenced by IL-6 signaling pathways, and significant in evaluating treatment efficacy for diseases characterized by chronic inflammation.\n", + "\n", + "================================================================================\n", + "24. sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw147d30ec_478e_4090_b496_128a131d29eb)\n", + "================================================================================\n", + "The species referred to as 'sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' appears to be a protein known as sgp130 located in a specific biological context (ID: mw147d30ec_478e_4090_b496_128a131d29eb). Here is a summary of the relevant background information:\n", + "\n", + "1. **Biological Function**: \n", + " sgp130 is a soluble form of gp130, which is a component of the IL-6 receptor complex. sgp130 acts by binding to the IL-6/sIL-6Rα complex, thereby inhibiting IL-6 trans-signaling. This function is crucial as IL-6 trans-signaling is associated with various inflammatory and autoimmune conditions.\n", + "\n", + "2. **Role in Pathways**:\n", + " sgp130 plays a role in the IL-6 signaling pathway by inhibiting the formation of active signaling complexes. This modulation of the pathway can potentially reduce inflammatory responses mediated through IL-6 trans-signaling.\n", + "\n", + "3. **Interactions with Other Molecules**:\n", + " sgp130 interacts specifically with the complex formed by IL-6 and its soluble receptor sIL-6Rα. By binding to this complex, sgp130 prevents the subsequent interaction with the membrane-bound gp130, effectively blocking signal transduction.\n", + "\n", + "4. **Importance in the Biological System Being Modeled**:\n", + " In the context of therapeutic applications, particularly for conditions such as Crohn's disease, sgp130 is evaluated for its potential use in inhibiting inflammatory signaling. Despite being present in large concentrations compared to IL-6, sensitivity analyses suggest that the therapeutic effectiveness of sgp130-based interventions may require very high doses due to its minimal impact on overall system dynamics at typical concentrations. This is because sgp130 naturally exists in excess relative to IL-6, limiting its impact when used in moderate amounts.\n", + "\n", + "5. **Relevance in Systems Biology Model**:\n", + " The systems biology model suggests that while sgp130 has a role, its overall impact on key output parameters (such as CRP levels) is limited unless used in substantial amounts. It highlights the need for potentially better therapeutic targets like IL-6 and sIL-6Rα, where alterations could more significantly affect system outputs.\n", + "\n", + "Overall, sgp130 serves a regulatory function in IL-6 mediated signaling, highlighting its role in inflammatory pathways but with suggested limitations for therapeutic application based on the systems biology model being considered.\n", + "\n", + "================================================================================\n", + "25. sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mwab41493c_6349_45f1_a226_3030cfed0e06)\n", + "================================================================================\n", + "Based on the provided context, the species 'sR_IL6_sgp130', identified by the ID mwab41493c_6349_45f1_a226_3030cfed0e06, appears to be related to a fusion protein that plays a role in inhibiting IL-6 trans-signaling pathways. This fusion protein, popularly referred to as sgp130Fc, combines the extracellular portion of glycoprotein 130 (gp130) with the Fc region of human IgG1. \n", + "\n", + "**Biological Function:**\n", + "sR_IL6_sgp130 acts to bind specifically to the IL-6/sIL-6Rα complex, which is pivotal in mediating IL-6 trans-signaling. By binding to this complex, it effectively prevents the signaling process that would typically activate downstream pathways, such as the phosphorylation of STAT3 (pSTAT3) and subsequent gene transcription.\n", + "\n", + "**Role in Pathways:**\n", + "Its primary role resides in the inhibition of IL-6 trans-signaling, which is critical in the context of inflammatory responses and diseases like Crohn’s disease. The simulations and models cited suggest that this species is involved in modifying the dose-response relationship of certain therapeutic interventions, leading to outcomes like CRP suppression.\n", + "\n", + "**Interactions with Other Molecules:**\n", + "sR_IL6_sgp130 interacts predominantly with the IL-6/sIL-6Rα complex. The sgp130 component has a high affinity for this complex, which is a major interaction through which it achieves its inhibitory functions.\n", + "\n", + "**Importance in the Biological System Being Modeled:**\n", + "In the system, while sR_IL6_sgp130 is present in high baseline levels and exerts limited effects on steady-state system dynamics due to its excess relative to free IL-6 concentrations, it remains a pivotal molecule for therapeutic applications. Its primary importance lies in its use as a potential therapeutic intervention, especially considered for conditions with elevated IL-6 trans-signaling, requiring very high and frequent doses to be effective due to its baseline levels.\n", + "\n", + "This summary indicates that sR_IL6_sgp130 is critical in the context of therapies aiming to modulate IL-6 signaling pathways, providing insights into the need for precise dosing strategies to achieve therapeutic benefits.\n", + "\n", + "================================================================================\n", + "26. Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mwf405687b_7401_44ec_a0d6_4a2b35c13e8a)\n", + "================================================================================\n", + "Based on the provided context, no specific information about the species named 'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' was found in the excerpts from the document. However, I can infer some potential characteristics and roles it might have based on general biological knowledge and the information typically associated with similar components.\n", + "\n", + "1. **Biological Function**: Generally, \"Ab\" in a biological context often refers to antibodies. If 'Ab_sR' is indeed an antibody or related to antibody activity, its function could be to bind to specific antigens, perhaps part of a signaling pathway or immune response mechanism.\n", + "\n", + "2. **Role in Pathways**: The context mentions IL-6 and its receptor interactions, which are part of immune signaling pathways. If 'Ab_sR' is interacting with such pathways, it could be modulating or inhibiting specific signals, particularly in inflammatory or immune responses.\n", + "\n", + "3. **Interactions with Other Molecules**: As the context heavily references IL-6, IL-6R, and associated signaling components like STAT3 and SOCS, it is plausible that 'Ab_sR' could interact with these molecules. It might bind to a receptor or signaling molecule to alter its activity.\n", + "\n", + "4. **Importance in the Biological System**: Assuming 'Ab_sR' is an antibody related to receptor activity, it could be crucial in modulating inflammatory responses or other cytokine-related pathways. In systems biology models, such antibodies are often used to simulate therapeutic interventions, inhibiting specific pathways to predict changes in disease states or therapeutic outcomes.\n", + "\n", + "Without explicit details from the document, these inferences remain general and speculative. Further details would be needed for precise characterization.\n", + "\n", + "================================================================================\n", + "27. Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw3667a5e1_02c9_44a0_acb4_b0431faa822d)\n", + "================================================================================\n", + "Based on the context provided, there isn't directly available specific information about the species named 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, we can infer its role based on general knowledge and the content present in the documents.\n", + "\n", + "1. **Biological Function:** 'Ab' likely refers to an antibody, given the context of medical and pharmacological studies. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects, such as bacteria and viruses.\n", + "\n", + "2. **Role in Pathways:** Antibodies are a crucial part of the immune response, often engaging in pathways related to immune regulation and inflammatory responses. Specifically, within the context, it seems to be involved in pathways targeting IL-6 or IL-6Rα, which are significant in inflammatory processes and immune system signaling, especially in conditions like inflammatory bowel diseases and other inflammatory responses.\n", + "\n", + "3. **Interactions with Other Molecules:** Within the context, the antibodies interact with IL-6 and sIL-6Rα (soluble IL-6 receptor alpha). These interactions are essential as they form complexes that are targets for therapeutic interventions to suppress inflammatory markers like C-reactive protein (CRP). The effectiveness of such interventions can vary based on whether IL-6 and its receptor are targeted individually or together.\n", + "\n", + "4. **Importance in the Biological System:** Antibodies, like the one inferred (potentially anti-IL-6 or similar), are important in modulating the immune response and are used in therapeutic settings to treat diseases where cytokine activity (like that of IL-6) is dysregulated. They help reduce undesirable inflammation and are thus a critical part of managing inflammatory diseases.\n", + "\n", + "In summary, while specific details about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' are not provided, it is most likely a therapeutic antibody involved in pathways targeting IL-6 and its receptor, pivotal in controlling inflammation within biological systems.\n", + "\n", + "================================================================================\n", + "28. Ab_R (ID: mw772cbf20_3fc1_4800_ae59_77884f1ae333)\n", + "================================================================================\n", + "The document provided does not explicitly mention the species 'Ab_R' with the ID 'mw772cbf20_3fc1_4800_ae59_77884f1ae333.' Therefore, I will infer what 'Ab_R' might pertain to based on the general knowledge presented in the context and common biological components.\n", + "\n", + "1. **Biological Function:**\n", + " - Given that the context mentions anti-IL-6 and anti-IL-6Rα antibodies, it is plausible that 'Ab_R' could represent an antibody (Ab) related to these immune system components. \n", + "\n", + "2. **Role in Pathways:**\n", + " - Antibodies targeting the IL-6/IL-6Rα pathway are involved in modulating inflammatory responses. IL-6 is a cytokine involved in immune regulation, and its receptor, IL-6Rα, can exist in both a soluble and membrane-bound form, playing roles in signaling cascades that promote inflammation.\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " - If 'Ab_R' is, in fact, an antibody similar to anti-IL-6 or anti-IL-6Rα, it would likely bind to these targets to inhibit cytokine signaling, thereby reducing inflammation. It may interact with IL-6, IL-6Rα, or both.\n", + "\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - The context of the document suggests a focus on modeling pharmacokinetics and pharmacodynamics (PK/PD) of antibodies targeting IL-6/IL-6Rα pathways, often to evaluate potential therapeutic interventions for conditions involving chronic inflammation, such as autoimmune diseases or inflammatory diseases like Crohn’s disease (CD).\n", + " - Such antibodies can serve as therapeutic agents to suppress the inflammatory response by antagonizing the IL-6 pathway, therefore reducing downstream effects like C-reactive protein (CRP) levels, which is a marker of inflammation.\n", + "\n", + "Conclusively, while the document does not provide direct information on 'Ab_R,' it is likely aligned with therapeutic antibodies targeting cytokine signaling pathways to control inflammation within a modeled biological framework.\n", + "\n", + "================================================================================\n", + "29. Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf)\n", + "================================================================================\n", + "The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned in the provided context. However, it is possible to infer details about this species based on the context and general knowledge about similar biological components, such as sIL-6R and IL-6.\n", + "\n", + "1. **Biological Function**: \n", + " - Since 'Ab_sR_IL6' likely refers to an antibody (Ab) targeting soluble IL-6 receptor (sIL-6R), its primary function would be to bind soluble IL-6R, potentially inhibiting its interaction with IL-6.\n", + "\n", + "2. **Role in Pathways**:\n", + " - In immune regulation pathways, particularly those involving interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R) can form complexes with IL-6 to mediate signaling even in cells that do not express membrane-bound IL-6R. By targeting sIL-6R, the antibody could disrupt these signaling cascades, serving as a potential therapeutic strategy in diseases characterized by excessive IL-6 signaling, such as rheumatoid arthritis or Crohn’s disease.\n", + "\n", + "3. **Interactions with Other Molecules**:\n", + " - Ab_sR_IL6 would primarily interact with sIL-6R, preventing it from binding to IL-6. This could impede the formation of the IL-6/sIL-6R complex, potentially reducing downstream signaling through the STAT3 pathway and other associated responses, such as C-reactive protein (CRP) production in the liver.\n", + "\n", + "4. **Importance in the Biological System Being Modeled**:\n", + " - In the context of a model focused on immune regulation, particularly in conditions like Crohn’s disease, targeting sIL-6R with an antibody could be critical in modulating the inflammatory response. By acting on the IL-6 signaling pathway, such an approach could help manage systemic inflammation and related symptoms.\n", + "\n", + "While there is no specific mention of 'Ab_sR_IL6' in the provided documents, understanding its potential role can be inferred based on known dynamics of IL-6, sIL-6R, and their involvement in immune and inflammatory processes.\n", + "\n", + "================================================================================\n", + "30. sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mw7becb5fe_8da8_4285_a821_0d77ad811b62)\n", + "================================================================================\n", + "Based on the provided context, there is no specific mention or detailed description of a species or molecule named 'sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, we can infer information about its potential biological role based on general knowledge of similar components in the context of the document, which discusses IL-6 signaling pathways.\n", + "\n", + "The document prominently features IL-6 (Interleukin-6) and its role in the context of immune regulation, particularly in relation to Crohn’s disease. IL-6 is a cytokine involved in inflammation and immune responses. It signals through two main pathways: classical signaling and trans-signaling. In classical signaling, IL-6 binds to its membrane-bound receptor, IL-6R, and subsequently recruits gp130, leading to the activation of downstream pathways such as the JAK/STAT pathway. In trans-signaling, IL-6 can also bind to a soluble form of its receptor, sIL-6R, allowing it to act on cells that do not express membrane-bound IL-6R.\n", + "\n", + "Given the emphasis on IL-6 and sIL-6R in the context, 'sR_IL6' could refer to a soluble receptor or a related soluble component in the IL-6 signaling pathway. This type of molecule typically facilitates trans-signaling interactions. It may interact with IL-6 to form a complex that can then engage with another component, sgp130, to modulate signaling. This complex plays a role in regulating immune responses and could have therapeutic implications, especially in diseases like Crohn’s disease where IL-6 signaling is dysregulated.\n", + "\n", + "In summary, if 'sR_IL6' is indeed related to IL-6 signaling, its biological importance might lie in modulating inflammatory responses through trans-signaling, interacting with IL-6 and possibly other soluble receptors or signaling molecules in this pathway. Its role would be crucial in maintaining homeostasis in immune function and could be a target for therapeutic interventions.\n", + "\n", + "================================================================================\n", + "31. gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca)\n", + "================================================================================\n", + "Based on the provided context, here is the summarized background information about the gp130 species:\n", + "\n", + "1. **Biological Function**: gp130 is a protein that plays a critical role in signaling pathways, specifically as part of the interleukin-6 (IL-6) signaling pathway. It acts as a key signal transducer and is involved in the formation of a signaling complex with the IL-6 receptor.\n", + "\n", + "2. **Role in Pathways**: gp130 is an integral component of the signaling complex formed between IL-6 and its soluble receptor, sIL-6Rα. The complex formation is crucial for IL-6 trans-signaling, which is implicated in various inflammatory responses.\n", + "\n", + "3. **Interactions with Other Molecules**: gp130 interacts with IL-6 and sIL-6Rα to form a hexameric complex that is necessary for initiating the downstream signaling cascade. Soluble gp130 (sgp130) acts as a natural inhibitor by binding to this complex, thereby preventing trans-signaling.\n", + "\n", + "4. **Importance in the Biological System**: In the context of the system being modeled, soluble gp130 (sgp130) is considered a potential therapeutic agent, especially in conditions like Crohn's disease, due to its ability to inhibit IL-6 trans-signaling. However, the effectiveness of sgp130 is dependent on achieving high and frequent doses, as small alterations in sgp130 levels have minimal impact due to its high baseline concentration relative to IL-6.\n", + "\n", + "Overall, gp130 is pivotal for IL-6-mediated signaling, and modifications in its activity can potentially modulate inflammatory pathways, making it a significant target in certain therapeutic approaches.\n", + "\n", + "================================================================================\n", + "32. R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9)\n", + "================================================================================\n", + "Based on the context provided, the species named 'R_IL6_gp130' appears to relate to the interleukin-6 (IL-6) signaling pathway, which involves the interaction of IL-6 with its receptor components for signal transduction. Although specific details about this species are not directly provided in the context, we can infer its characteristics and role based on the general knowledge of similar biological components involved in IL-6 signaling:\n", + "\n", + "1. **Biological Function**: R_IL6_gp130 likely represents a complex involving IL-6, its specific receptor, and the signal transducer gp130. In the IL-6 signaling pathway, gp130 serves as a critical signal transducer that, upon activation by the IL-6/IL-6 receptor complex, initiates intracellular signaling cascades that influence gene expression.\n", + "\n", + "2. **Role in Pathways**: This species is part of the IL-6 signaling pathway, which can activate the JAK/STAT signaling cascade, resulting in the phosphorylation of STAT3 (Signal Transducer and Activator of Transcription 3). This pathway is crucial in mediating inflammatory responses and plays a role in various physiological and pathological processes, including immune regulation, inflammation, and cell growth.\n", + "\n", + "3. **Interactions with Other Molecules**: R_IL6_gp130 likely interacts with IL-6 and its soluble receptor (sIL-6R), as well as with gp130. This interaction forms a complex that facilitates signal transduction through the gp130 component, leading to downstream effects such as the activation of STAT3. It can also interact with inhibitors like soluble gp130 (sgp130) or fusion proteins designed to modulate this signaling pathway.\n", + "\n", + "4. **Importance in the Biological System**: Within the context described, R_IL6_gp130 is important for understanding the dynamics of IL-6 signaling, especially in inflammatory conditions such as Crohn's disease. The IL-6 pathway is targeted for therapeutic intervention, suggesting its significance in disease pathology and treatment.\n", + "\n", + "In summary, R_IL6_gp130 likely represents a key component of the IL-6 signaling pathway, central to mediating the effects of IL-6 through gp130 in inflammation and immune response, as inferred from the general function of similar complexes.\n", + "\n", + "================================================================================\n", + "33. Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw6cce2109_0e32_4dd9_98ec_41173e8ef07d)\n", + "================================================================================\n", + "Based on the provided context, there appears to be no specific information about the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' within the text. However, the context discusses the IL-6 signaling pathway and its components, particularly focusing on the interactions between IL-6, sIL-6Rα, and therapeutic antibodies, such as the humanized anti-interleukin 6 receptor antibody (tocilizumab). This suggests a theme centered around immune response regulation, specifically in diseases like rheumatoid arthritis and possibly Crohn's disease.\n", + "\n", + "In the absence of specific information about 'Ractive', we can infer its potential role based on the discussed biological components. It is likely that 'Ractive' could be involved in the pathways related to cytokine signaling, immune modulation, or therapeutic interactions similar to those of IL-6 or its receptor complex. Its importance in the system may be linked to modulating immune responses or serving as a target or mediator in therapeutic approaches within the context of the mentioned diseases.\n", + "\n", + "In systems biology modeling, species or molecules like 'Ractive' could be critical for either transmitting signals within a pathway, modifying the activity of other molecules, or acting as a checkpoint or target for drugs designed to alter biological responses in conditions like Crohn's disease or rheumatoid arthritis.\n", + "\n", + "================================================================================\n", + "34. STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw2b255f94_8018_4b99_bde8_918eeac45446)\n", + "================================================================================\n", + "Based on the provided context, the species 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is likely referring to the well-known protein STAT3, a signal transducer and activator of transcription 3. Here is the relevant background information about STAT3:\n", + "\n", + "1. **Biological Function**:\n", + " - STAT3 is involved in the phosphorylation process as part of cell signaling. Phosphorylated STAT3 (pSTAT3) is indicative of its active state, which can translocate to the nucleus to act as a transcription factor.\n", + " - It plays a crucial role in relaying signals from cytokine receptors, like the IL-6 receptor complex, to the nucleus, influencing gene expression.\n", + "\n", + "2. **Role in Pathways**:\n", + " - STAT3 is a central component of the JAK-STAT signaling pathway. Once activated, it typically mediates the effects of cytokines, such as IL-6, contributing to various cellular responses, including growth, differentiation, and survival.\n", + " - The context mentions its involvement in pathways activated by IL-6, a cytokine that triggers immune responses, inflammation, and acute-phase reactions.\n", + "\n", + "3. **Interactions with Other Molecules**:\n", + " - STAT3 gets activated by cytokines binding to their respective receptors, leading to JAK kinases' activation, which subsequently phosphorylates STAT3.\n", + " - It interacts with components of the IL-6 receptor family, specifically affecting the pathways involving IL-6 trans-signaling.\n", + " - The context also suggests interactions involving sIL-6R (a soluble IL-6 receptor) and sgp130 (a soluble form of the co-receptor gp130), where pSTAT3 acts in various compartments like the GI tract and liver depending on cytokine signaling.\n", + "\n", + "4. **Importance in the Biological System**:\n", + " - STAT3 is important in modeling biological systems that involve immune responses or inflammation, such as in the context of Crohn's disease, as indicated by increased pSTAT3 levels in serum and tissues affected by the disease.\n", + " - Its role as a transcription factor makes it key in regulating downstream gene expression that could contribute to disease pathology and the body's response to inflammation.\n", + "\n", + "In summary, although there is no direct mention of a species specifically labeled 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' in the document, the general characteristics and functions of STAT3 can be inferred based on common scientific knowledge and the provided context about IL-6 signaling and related pathways.\n", + "\n", + "================================================================================\n", + "35. pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw48867e93_f170_44e8_ac7a_185b23e1bf3b)\n", + "================================================================================\n", + "Based on the context provided, specific information about the biological species 'pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is not explicitly detailed. However, we can infer its role and significance based on the general knowledge about pSTAT3 and its involvement in biological processes.\n", + "\n", + "1. **Biological Function:**\n", + " - pSTAT3, or phosphorylated STAT3, is a form of Signal Transducer and Activator of Transcription 3 (STAT3) that becomes activated through phosphorylation. This activation enables pSTAT3 to translocate to the cell nucleus, where it functions as a transcription factor, promoting the expression of various genes involved in cell growth, survival, and differentiation.\n", + "\n", + "2. **Role in Pathways:**\n", + " - In the context described, pSTAT3 is associated with IL-6 signaling, which involves classical and trans-signaling pathways. IL-6 is a cytokine involved in immune response, and its interaction with receptors such as IL-6R and gp130 leads to the activation of JAK kinases and subsequent phosphorylation of STAT3 (pSTAT3). This signaling cascade is crucial in mediating responses to inflammation and stress.\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " - pSTAT3 interacts with the IL-6 receptor complex, including sIL-6R (soluble IL-6 receptor) and sgp130 (soluble gp130). The complex formation and subsequent signaling facilitate various downstream effects. pSTAT3 is known to regulate the expression of suppressor of cytokine signaling (SOCS) proteins and other gene products involved in modulating immune responses.\n", + "\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - pSTAT3 plays a critical role in inflammatory responses, as highlighted by its reported increase in serum concentrations in conditions like Crohn’s disease. It is involved in the transcriptional regulation of acute-phase proteins such as C-reactive protein (CRP) and other gene products that are significant in the immune response and inflammation within the gastrointestinal tract and liver.\n", + "\n", + "This inferred information helps underscore the importance of pSTAT3 in immune modulation and its potential implications in inflammatory diseases, even though specific details about its ID-specific characteristics in the context were not provided.\n", + "\n", + "================================================================================\n", + "36. geneProduct (ID: mw0083d743_836f_4238_a17f_4602193d5bc0)\n", + "================================================================================\n", + "The provided context from the document does not include specific details about the biological species or molecule identified as 'geneProduct' with the ID: mw0083d743_836f_4238_a17f_4602193d5bc0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. There is no explicit mention of this molecule's biological function, role in pathways, interactions with other molecules, or its importance in the biological system being modeled.\n", + "\n", + "Based on the context, which predominantly discusses interleukin-6 (IL-6) pathways, receptors, and related molecules (e.g., sIL-6R, gp130, and sgp130), we can infer that 'geneProduct' might be related to the IL-6 signaling pathway or another signaling molecule involved in inflammatory or immune responses. In systems biologically concerned with inflammation or cytokine signaling, such gene products might typically be involved in cell signaling cascades, playing roles in activating transcription factors, interacting with receptors or co-receptors, and affecting the expression of downstream genes important for cellular responses.\n", + "\n", + "Since specific data is not available, hypothetical pathways could involve roles similar to those of IL-6 or its receptors—modulating inflammatory responses, and participating in acute phase reactions, including CRP production in the liver. Gene products in such pathways often interact with other cytokines, receptors, and intracellular signaling proteins to exert their effects, potentially influencing processes like cell proliferation, differentiation, and survival.\n", + "\n", + "================================================================================\n", + "37. sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mwd31f52cc_04e7_40e0_885f_c7b2d9e62215)\n", + "================================================================================\n", + "Based on the context provided, there is no explicit mention of the species 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' directly in the excerpts. However, we can infer some related information using general knowledge and by examining the related components and interactions in the context shared.\n", + "\n", + "The context revolves around the interaction and dynamics involving the Interleukin-6 (IL-6) signaling pathway, soluble IL-6 receptor (sIL-6R), and the involvement of other molecules like sgp130. \n", + "\n", + "### Inferred Background Information about 'sR':\n", + "\n", + "1. **Biological Function:**\n", + " - In the context of cytokine signaling, receptors like sR are generally involved in recognizing and binding to specific signaling molecules (e.g., cytokines such as IL-6) to facilitate their biological functions. Therefore, 'sR' could act as a receptor or part of a receptor complex in signaling pathways.\n", + "\n", + "2. **Role in Pathways:**\n", + " - Given the presence of IL-6 and its receptor dynamics (e.g., IL-6/sIL-6R complex) in the context, 'sR' might participate in cytokine signaling pathways, potentially serving as a modulator that enhances or inhibits signal transduction depending on its specific interactions with IL-6 or other pathway components like sgp130.\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " - The sIL-6R forms complexes with IL-6, which then interact with membrane-bound receptors to initiate signaling cascades like the activation of STAT3. 'sR' might potentially interact similarly, indicating a critical role in modifying the intensity or outcome of the signaling process.\n", + "\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - The balance of soluble receptors and cytokines (such as IL-6/sIL-6R) and their interactions with other molecules (e.g., sgp130) are essential for controlling inflammatory responses and other downstream effects (e.g., CRP production in the liver).\n", + " - Given this, 'sR' could play a pivotal regulatory role, affecting the system's sensitivity to changes in cytokine levels and potentially serving as a target for therapeutic interventions.\n", + "\n", + "### Conclusion:\n", + "\n", + "While the provided document excerpts do not explicitly detail 'sR's identity or function, its inferred associations with key players like IL-6, sIL-6R, and sgp130 suggest a role in cytokine signaling modulation, particularly in pathways relevant to inflammation and immune response. For specific molecular functions and pathway roles, further examination of full-length documents or additional sources would be required.\n", + "\n", + "================================================================================\n", + "38. IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mw2c9b0499_3325_4394_8af3_bbf653a944a0)\n", + "================================================================================\n", + "Based on the provided context and general knowledge, the species named 'IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' is likely referring to Interleukin-6 (IL-6), a cytokine involved in various biological functions and pathways. Here is a summary of its roles and significance:\n", + "\n", + "1. **Biological Function:**\n", + " - IL-6 is a multifunctional cytokine that plays a critical role in immune response regulation, inflammation, and hematopoiesis.\n", + " - It is known to be a mediator of fever and of the acute phase response.\n", + "\n", + "2. **Role in Pathways:**\n", + " - IL-6 signaling occurs via two main pathways: the classical signaling pathway and the trans-signaling pathway.\n", + " - The classical pathway involves IL-6 binding to a membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of IL-6Rα (sIL-6Rα).\n", + " - Both pathways converge on a signal transduction cascade that activates Janus kinase (Jak) proteins and leads to the phosphorylation of signal transducer and activator of transcription 3 (STAT3).\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " - IL-6 interacts with its receptor IL-6Rα (either membrane-bound or soluble) and forms a complex that recruits the gp130 coreceptor.\n", + " - This interaction is crucial for activating downstream signaling pathways that are involved in immune responses.\n", + "\n", + "4. **Importance in the Biological System:**\n", + " - IL-6 is particularly important in inflammatory diseases such as Crohn's disease, where it contributes to enhanced T-cell survival and resistance to apoptosis in the intestinal mucosa, as well as elevated chemokine secretion.\n", + " - It plays a significant role in the pathophysiology of autoimmune diseases and chronic inflammatory conditions, making it a target for therapeutic interventions such as with specific antibodies like tocilizumab.\n", + "\n", + "In summary, IL-6 is a central cytokine in immune regulation and inflammatory processes, which makes it a pivotal part of the biological system being modeled, particularly in the context of diseases like Crohn's disease.\n", + "\n", + "================================================================================\n", + "39. sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mwd65b5b39_dc1b_4e77_a999_67277a880e5e)\n", + "================================================================================\n", + "Based on the provided context, here is the background information about the species 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)':\n", + "\n", + "### Biological Function:\n", + "sgp130, known here as a species variant, reflects a biological molecule related to the inhibition of IL-6 trans-signaling. It specifically refers to a fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is designed to inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex.\n", + "\n", + "### Role in Pathways:\n", + "sgp130 plays a role in pathways involving the interleukin-6 (IL-6) signaling cascade. It specifically targets the IL-6/sIL-6Rα complex, blocking the trans-signaling pathway that can contribute to inflammatory responses, such as those observed in Crohn’s disease.\n", + "\n", + "### Interactions with Other Molecules:\n", + "sgp130 interacts with the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc binds this complex with the same affinity as natural sgp130, thus inhibiting the signaling pathways mediated by IL-6.\n", + "\n", + "### Importance in the Biological System:\n", + "sgp130 appears to be of limited effect in altering the steady-state values of certain biomarkers unless present in large quantities. It exists in excess compared to free IL-6, leading to minimal effect from small perturbations in its levels. Hence, any significant observable effects require substantial changes in sgp130 concentrations.\n", + "\n", + "Despite its biological function, the context suggests that sgp130-based therapeutic strategies may not be as robust as anticipated. The sensitivity analysis indicated that the output biomarkers are less affected by sgp130 levels, making IL-6 and sIL-6Rα more potent targets for intervention in the studied system. This contributes to understanding its therapeutic potential limitations, particularly in addressing diseases like Crohn's where IL-6 signaling is implicated.\n", + "\n", + "================================================================================\n", + "40. sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3)\n", + "================================================================================\n", + "The species sR_IL6_sgp130, identified as mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 within the context provided, appears to involve components related to interleukin-6 (IL-6) signaling pathways. Here is the summary of the background based on the given context and general knowledge:\n", + "\n", + "### Biological Function\n", + "- **Fusion Protein**: The document mentions a fusion protein involving sgp130, which combines the extracellular portion of the gp130 protein with the Fc region of human IgG1. This fusion protein, known as sgp130Fc, is designed to inhibit IL-6 trans-signaling in cells.\n", "\n", - "The active hexameric IL-6 receptor complex leads to the phosphorylation of gp130-bound Janus kinase (Jak) family proteins and subsequent activation of signal transducer and activator of transcription 3 (STAT3) via phosphorylation. This signaling is implicated in inflammation and autoimmunity processes, which are central to the pathology of Crohn's disease. \n", + "### Role in Pathways\n", + "- **IL-6 Trans-Signaling**: The primary role of sgp130Fc is to inhibit IL-6 trans-signaling. In the IL-6 signaling pathway, IL-6 can signal through its receptor complex involving IL-6R and gp130, leading to downstream effects such as the activation of STAT3 transcription factors. The fusion protein acts to prevent this signaling pathway by binding to the IL-6/sIL-6Rα complex.\n", + "- **Simulations in Crohn’s Disease**: The sgp130Fc protein is being studied for its therapeutic potential in inflammatory conditions like Crohn’s disease, where IL-6 signaling plays a significant role.\n", "\n", - "Additionally, the model discussed in the provided context focuses on the pharmacokinetics and dynamics of anti–IL-6 and anti–IL-6Rα antibodies, such as tocilizumab, used in the treatment of autoimmune diseases like rheumatoid arthritis. These antibodies target the IL-6 pathways, particularly affecting how IL-6 signaling is modulated, and the model attempts to understand the therapeutic impact and dosing regimens of these biologics.\n", + "### Interactions with Other Molecules\n", + "- **Binding with IL-6/sIL-6Rα Complex**: The sgp130Fc is assumed to bind with the IL-6/sIL-6Rα complex with affinities similar to natural sgp130. The presence of sgp130Fc in large quantities suggests it primarily functions by excess binding to this complex, thereby preventing excessive IL-6 signaling.\n", "\n", - "Overall, IL6 is critical in immune regulation and is a key target for therapeutic intervention in diseases characterized by dysregulated immune responses.\n" + "### Importance in the Biological System\n", + "- **Therapeutic Potential**: The document outlines the use of sgp130Fc as a potential therapeutic intervention in diseases with aberrant IL-6 signaling, such as Crohn’s disease. It has been shown to only be effective at very high doses due to its interaction landscape.\n", + "- **Limited Systemic Impact**: Due to high baseline levels of sgp130 compared to IL-6, small changes in sgp130 do not significantly affect the system, implying its role predominantly emerges under conditions requiring high-dose applications or alterations.\n", + "\n", + "Overall, while the document primarily discusses the use of a related molecule (sgp130Fc), it emphasizes the relevance of sgp130 interactions within IL-6-related pathways, underscoring its importance in modulating immune and inflammatory responses within certain pathological contexts.\n", + "\n", + "================================================================================\n", + "41. Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mwf7796221_1fea_4274_a93e_c00adbf5778c)\n", + "================================================================================\n", + "Based on the provided context, there is no specific detailed information available about the species or molecule 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' with the ID mwf7796221_1fea_4274_a93e_c00adbf5778c. However, from the context and general knowledge, we can infer the following:\n", + "\n", + "1. **Biological Function**: The document references serum antibody (Ab) concentrations in nmol/l, which suggests that 'Ab' likely stands for an antibody. Antibodies are proteins produced by the immune system to identify and neutralize pathogens such as bacteria and viruses.\n", + "\n", + "2. **Role in Pathways**: The context mentions anti-IL-6/sIL-6Rα interactions. Antibodies targeting the interleukin-6 (IL-6) pathway are typically used in treatments to modulate immune responses, particularly in inflammatory conditions. They can bind to IL-6 or its receptor to inhibit the downstream signaling pathway.\n", + "\n", + "3. **Interactions with Other Molecules**: The document discusses the anti-IL-6 Ab's effect in relation to IL-6 and sIL-6Rα. This suggests that the antibody in question interacts specifically with these cytokines or cytokine receptors, playing a role in reducing inflammation by interfering with the IL-6 signaling pathway.\n", + "\n", + "4. **Importance in the Biological System**: The antibody’s importance seems to be related to its therapeutic role in modulating the immune response, particularly in diseases involving heavy inflammation. This can include conditions like inflammatory bowel diseases or other autoimmune disorders, where targeting IL-6 or its receptor can have significant therapeutic effects.\n", + "\n", + "In summary, based on the context and typical characteristics of antibodies in similar biological systems, 'Ab' is likely an antibody involved in targeting the IL-6 signaling pathway, important for managing inflammatory responses in various conditions.\n", + "\n", + "================================================================================\n", + "42. Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mw5d764bb8_5693_4ac8_9557_f65992cc5eb0)\n", + "================================================================================\n", + "Based on the provided context, there is no specific mention or details about the species named 'Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, I can infer potential roles and functions based on adjacent biological components and typical interactions within such systems, especially considering the discussion around IL-6 pathways and related molecules in the context.\n", + "\n", + "1. **Biological Function**: In this particular study context, sIL-6R (soluble Interleukin-6 receptor) and IL-6 (a cytokine involved in inflammation and immune responses) are key components. Ab_sR might refer to an antibody-related soluble receptor component or variant. If related to IL-6/sIL-6R pathways, its function could involve modulation of immune responses or inflammation via binding interactions.\n", + "\n", + "2. **Role in Pathways**: The surrounding context heavily discusses the interaction of IL-6 with its receptor and the subsequent signaling pathways, such as the Jak-STAT pathway (notably leading to STAT3 activation), indicating a role in cytokine-receptor interactions. Ab_sR could interact within these pathways, perhaps as an intermediary or a modulator influencing signal transduction.\n", + "\n", + "3. **Interactions with Other Molecules**: If analogous to sIL-6R or anti-IL-6 therapeutic antibodies, Ab_sR might interact with IL-6, potentially modulating its effects by altered binding dynamics or competitive inhibition. Such interactions could influence downstream signaling events leading to transcriptional changes (e.g., expression of SOCS or CRP).\n", + "\n", + "4. **Importance in Biological System Being Modeled**: In systems modeling inflammatory responses, any component similar to an antibody interacting with cytokines like IL-6 is critical. It could predictively simulate treatment outcomes for inflammatory diseases or evaluate drug efficacy (e.g., CRP suppression in inflammatory cases). Ab_sR may hold similar significance if it's part of experimental or theoretical models assessing cytokine network modulation.\n", + "\n", + "While these are educated guesses based on typical roles and interactions of analogous proteins within such biological systems, exact functions and roles of Ab_sR would be best determined by specifics from the cited source text.\n", + "\n", + "================================================================================\n", + "43. Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2)\n", + "================================================================================\n", + "The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2) does not have specific background information provided explicitly in the context you shared. However, I can infer potential characteristics based on general knowledge about similar components.\n", + "\n", + "### Inferred Background Information:\n", + "\n", + "1. **Biological Function:**\n", + " - 'Ab_sR_IL6' likely refers to an antibody ('Ab') targeting the soluble form of the interleukin-6 receptor (sIL-6R). This suggests it is involved in neutralizing or modulating the biological effects of sIL-6R, potentially inhibiting its interaction with interleukin-6 (IL-6).\n", + "\n", + "2. **Role in Pathways:**\n", + " - The context described the targeting of the IL-6/sIL-6R complex as a treatment strategy for conditions involving excessive IL-6 signaling, such as Crohn's disease. 'Ab_sR_IL6' might play a role in suppressing IL-6-mediated pathways, thereby reducing inflammation or immune responses associated with diseases like Crohn's disease or rheumatoid arthritis.\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " - Interacts with sIL-6R, preventing the formation of the IL-6/sIL-6R complex. This interaction would diminish the activity of the classical and trans-signaling pathways mediated by IL-6, leading to reduced activation of downstream signaling molecules like STAT3 and associated gene transcription.\n", + "\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - Its importance lies in modulating inflammation by impacting IL-6 signaling. As IL-6 is crucial in immune response modulation, controlling its activity can lead to therapeutic benefits in diseases characterized by inflammation and immune dysregulation.\n", + "\n", + "Broadly, 'Ab_sR_IL6' serves as a critical component in therapeutic models aiming to attenuate aberrant IL-6 signaling pathways in immune-mediated diseases.\n", + "\n", + "================================================================================\n", + "44. Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4) (ID: mwbc2f5464_81e5_43fd_8b39_f5a2756af72f)\n", + "================================================================================\n", + "The provided context does not contain direct information specifically about the species 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, from the available information, we can infer some details based on the general context and related biological components mentioned:\n", + "\n", + "1. **Biological Function**: The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects like bacteria and viruses. They play a crucial role in targeting specific antigens for the immune response.\n", + "\n", + "2. **Role in Pathways**: The context discusses the interaction between anti-IL-6 antibodies and IL-6/sIL-6Rα complex. IL-6 is a cytokine involved in inflammation and infection responses. Hence, antibodies targeting IL-6 pathways are often part of therapeutic interventions for inflammatory diseases.\n", + "\n", + "3. **Interactions with Other Molecules**: The document mentions the targeting of IL-6 and IL-6/sIL-6Rα complexes, suggesting that this antibody interacts with these molecules, likely inhibiting their function to reduce inflammation as indicated by the suppression of CRP (C-reactive protein), a marker of inflammation.\n", + "\n", + "4. **Importance in the Biological System Being Modeled**: The antibody's role appears to be significant in modulating inflammatory responses by targeting key molecular pathways involving IL-6 and its receptors. This indicates its potential therapeutic value in treating conditions where IL-6 is implicated, such as autoimmune or inflammatory diseases.\n", + "\n", + "In summary, while the antibody 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)' is not directly described in the context, inferred information suggests it likely functions as an IL-6 pathway inhibitor in an inflammatory response model, emphasizing its role in treatment strategies aimed at modulating immune responses.\n" ] } ], @@ -338,7 +1711,222 @@ " 'name': 'IL6',\n", " 'original_name': 'IL6',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"IL6, or Interleukin 6, is a cytokine that plays a significant role in the immune system. It is particularly important in the context of Crohn's disease, as it contributes to enhanced T-cell survival and apoptosis resistance in the lamina propria, along with increased chemokine secretion. IL-6 signaling occurs through two pathways: the classical pathway mediated by the membrane-bound IL-6 receptor (IL-6Rα) and the trans-signaling pathway mediated by the soluble IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of the gp130 coreceptor to form a receptor complex that initiates downstream signaling cascades.\\n\\nThe active hexameric IL-6 receptor complex leads to the phosphorylation of gp130-bound Janus kinase (Jak) family proteins and subsequent activation of signal transducer and activator of transcription 3 (STAT3) via phosphorylation. This signaling is implicated in inflammation and autoimmunity processes, which are central to the pathology of Crohn's disease. \\n\\nAdditionally, the model discussed in the provided context focuses on the pharmacokinetics and dynamics of anti–IL-6 and anti–IL-6Rα antibodies, such as tocilizumab, used in the treatment of autoimmune diseases like rheumatoid arthritis. These antibodies target the IL-6 pathways, particularly affecting how IL-6 signaling is modulated, and the model attempts to understand the therapeutic impact and dosing regimens of these biologics.\\n\\nOverall, IL6 is critical in immune regulation and is a key target for therapeutic intervention in diseases characterized by dysregulated immune responses.\"}]" + " 'background': \"The provided context outlines the biological function and role of IL-6, a cytokine important in the immune system. Based on the information:\\n\\n1. **Biological Function**:\\n IL-6 is a cytokine involved in immune regulation. It plays a crucial role in enhancing T-cell survival and resistance to apoptosis, particularly in the context of Crohn’s Disease, as well as in promoting chemokine secretion.\\n\\n2. **Role in Pathways**:\\n IL-6 signaling can proceed via two distinct pathways:\\n - The classical pathway, which involves the membrane-bound IL-6 receptor (IL-6Rα).\\n - The trans-signaling pathway, which involves a soluble IL-6 receptor (sIL-6Rα). In both pathways, IL-6 forms a complex with its respective receptor, which then recruits the gp130 coreceptor, leading to the formation of a hexameric receptor complex. This complex initiates phosphorylation of gp130-bound Janus kinase (Jak) proteins and subsequent activation of STAT3 (Signal Transducer and Activator of Transcription 3).\\n\\n3. **Interactions with Other Molecules**:\\n IL-6 interacts with its membrane-bound and soluble receptors to initiate signaling. The interaction sequence involves IL-6 binding to IL-6Rα, recruiting gp130, and activating downstream signaling molecules like Jak family proteins and STAT3.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n IL-6 is highlighted as a significant contributor in the pathophysiology of Crohn’s Disease due to its roles in promoting immune cell activities that lead to inflammation. The ability of IL-6 to engage in both classical and trans-signaling pathways suggests it is a versatile mediator in inflammatory processes, making it a critical target for therapeutic interventions.\\n\\n5. **General Knowledge and Inference**:\\n Beyond the context, IL-6 is generally known to be involved in inflammation and is a key player in various inflammatory diseases. It is a target for drugs like tocilizumab, which inhibit IL-6 signaling by preventing the interaction of IL-6 with its receptor, thus being an important therapeutic strategy in diseases such as rheumatoid arthritis.\\n\\nIn summary, IL-6 is a multifunctional cytokine central to immune regulation and inflammation, making it a crucial element in disease models, particularly those addressing inflammatory conditions like Crohn's Disease.\"},\n", + " {'id': 'mwbbbce920_e8dd_4320_9386_fc94bfb2fc99',\n", + " 'name': 'sgp130',\n", + " 'original_name': 'sgp130',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': 'Based on the context provided, sgp130 is a biological molecule that plays a role in inhibiting IL-6 trans-signaling. Here is a summary of its background information:\\n\\n1. **Biological Function**: sgp130 is derived from the extracellular portion of the gp130 protein. It serves to inhibit the signaling pathway of interleukin-6 (IL-6) by binding to the IL-6/sIL-6Rα complex, thereby preventing it from activating downstream signaling pathways. This inhibition is achieved by a fusion protein called sgp130Fc, which combines sgp130 with the Fc region of human IgG1.\\n\\n2. **Role in Pathways**: sgp130 influences the IL-6 signaling pathway, specifically targeting the trans-signaling aspect. IL-6 is a pro-inflammatory cytokine that can signal through a complex with soluble IL-6 receptor (sIL-6Rα) and gp130. By interfering with this pathway, sgp130 can modulate inflammatory responses.\\n\\n3. **Interactions with Other Molecules**: The primary interaction of sgp130 is with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 inhibits its ability to signal through the cell surface-bound gp130, thus blocking IL-6 mediated effects. The interaction between sgp130 and the IL-6/sIL-6Rα complex is central to its function.\\n\\n4. **Importance in the Biological System Being Modeled**: While sgp130 can effectively inhibit IL-6 trans-signaling, the context indicates that its role in the system being modeled is limited. The sensitivity analysis within the model shows that alterations in sgp130 levels have minimal effects on the steady-state values of output parameters due to the high baseline level of sgp130 compared to the relatively low concentration of free IL-6. This suggests that sgp130-based therapies may not be as impactful unless used at high and frequent doses. The model under discussion aimed at simulating its potential therapeutic use in conditions like Crohn’s disease.\\n\\nOverall, sgp130 is important for modulating IL-6 trans-signaling, but in the specific system modeled, its impact is limited under normal conditions due to its already high concentration compared to IL-6.'},\n", + " {'id': 'mw810ff751_fa4e_4143_bd50_169b3e325e1e',\n", + " 'name': 'sR_IL6_sgp130',\n", + " 'original_name': 'sR_IL6_sgp130',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': \"Based on the provided context from the document, 'sR_IL6_sgp130' seems to be a part of the IL-6 signaling pathway and is likely a reference to a complex involving soluble IL-6 receptor components. Here's a summary based on the information provided and general knowledge:\\n\\n- **Biological Function:** The complex is involved in modulating IL-6 signaling, particularly influencing the trans-signaling mechanism. Soluble gp130 (sgp130) acts as a natural inhibitor of IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing it from associating with membrane-bound gp130, which is necessary for signal transduction.\\n\\n- **Role in Pathways:** It is a critical modulator in the IL-6 signaling pathway. Normally, IL-6 binds to the soluble IL-6 receptor (sIL-6R), and this complex can further engage with gp130 on cell surfaces to propagate downstream signaling events. The sgp130 serves as a sink for these IL-6/sIL-6R complexes, limiting their ability to bind to cellular gp130 and hence reducing downstream signaling such as STAT3 activation.\\n\\n- **Interactions with Other Molecules:** The complex interacts primarily with IL-6 and its soluble receptor (sIL-6R). It prevents these molecules from engaging with cell-surface gp130, thus acting as a competitive inhibitor in the pathway.\\n\\n- **Importance in the Biological System:** In the context of the system being modeled, sgp130 is crucial as it regulates the balance of IL-6 signaling. Its high baseline concentration relative to IL-6 suggests it plays a stabilization role in keeping the system responsive only to significant changes in IL-6 levels. However, its effectiveness as a therapeutic agent, such as in Crohn’s disease, may require high and frequent dosing due to its large baseline presence and minimal effect on system dynamics under normal conditions.\\n\\nNo direct information about 'sR_IL6_sgp130' as a separate distinct entity is found in the context, suggesting it might be inferred from understanding sgp130's complex with IL-6 and sIL-6R within the described signaling and therapeutic contexts.\"},\n", + " {'id': 'mw114aa90f_5f5b_4fe8_9406_361c8489b6a1',\n", + " 'name': 'CRP',\n", + " 'original_name': 'CRP',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': \"The term 'CRP' within the context provided refers to C-reactive protein, rather than a distinct biological species. C-reactive protein is a well-known biomarker present in the bloodstream, often used to assess inflammation within the body. Here's a summary of relevant background information about CRP based on the context and general biological understanding:\\n\\n- **Biological Function**: C-reactive protein is an acute-phase protein produced by the liver in response to inflammation. Its primary role is to bind to the surface of dead or dying cells (and some types of bacteria) to activate the complement system, thereby promoting phagocytosis by macrophages. This function is part of the body's innate immune response, aiding in clearing pathogens and dead cells from the bloodstream.\\n\\n- **Role in Pathways**: CRP is part of the body's acute-phase response to inflammation. Its levels in the blood increase rapidly in response to inflammatory cytokines, such as interleukin-6 (IL-6). This makes CRP an integral component in pathways related to the immune system's response to infection, injury, or chronic inflammatory diseases.\\n\\n- **Interactions with Other Molecules**: CRP interacts with the complement system components, particularly C1q, to initiate the complement cascade, a series of reactions that help eliminate pathogens. It also interacts with receptors on the surfaces of immune cells, such as Fcγ receptors, facilitating opsonization and phagocytosis. The document mentions interactions with IL-6 and its receptor IL-6Rα, as CRP production is highly influenced by IL-6 signaling.\\n\\n- **Importance in Biological Systems**: In the context of the model described, CRP is used as a biomarker to assess inflammation levels in patients, particularly those with conditions such as Crohn's disease. The model measures CRP levels to validate its predictions regarding drug effects on inflammatory pathways, highlighting its utility in monitoring disease activity and treatment efficacy.\\n\\nOverall, CRP is a crucial component in biological models focused on inflammatory diseases due to its rapid and measurable response to changes in underlying inflammation.\"},\n", + " {'id': 'mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc',\n", + " 'name': 'sR',\n", + " 'original_name': 'sR',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': \"Based on the provided context, the species named 'sR' (ID: mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc) is likely related to the IL-6 signaling pathway. However, specific details about 'sR' are not provided directly in the context. Given that 'sR' is mentioned alongside IL-6, sIL-6R, and sgp130, it could be inferred that 'sR' is a component or modifier in the interleukin-6 (IL-6) signaling pathway.\\n\\n### Inferred Background Information\\n\\n**Biological Function**:\\n- It is probable that 'sR' is related to IL-6 signaling, potentially as a soluble receptor or co-receptor. Soluble receptors often exist as naturally occurring antagonists or helpers of cytokine signaling, modulating the pathway's activity.\\n\\n**Role in Pathways**:\\n- 'sR' might be involved in modulating the availability or activity of IL-6, similar to how sgp130 and sIL-6R work. sIL-6R is known to allow cells that do not possess membrane-bound IL-6R to respond to IL-6 through a process known as trans-signaling.\\n\\n**Interactions with Other Molecules**:\\n- It may interact with IL-6 or IL-6 receptor complexes. This interaction is crucial in the modulation of the pathway, likely affecting the downstream signaling events such as the activation of STAT3 (Signal Transducer and Activator of Transcription 3).\\n\\n**Importance in the Biological System**:\\n- Given its potential role in cytokine signaling, 'sR' would be important in regulating inflammatory responses, immune system signaling, and possibly in the pathophysiology of diseases where IL-6 is a key player, such as autoimmune diseases.\\n\\n### Contextual Consideration\\n- The provided context includes a discussion on sensitivity analysis and the role of sgp130 with IL-6, which highlights the intricate balance within the cytokine signaling pathways. Though 'sR' is not explicitly expanded upon, understanding the dynamics of similar molecules like sIL-6R and sgp130 offers insights into its potential biological significance.\\n \\nThis inferred information aligns with typical roles of soluble cytokine receptors in biological systems. However, the exact nature and function of 'sR' would require further specific details or experimental data.\"},\n", + " {'id': 'mw03db56ac_8dc6_4931_ae82_fef706d2ee3d',\n", + " 'name': 'sR_IL6',\n", + " 'original_name': 'sR_IL6',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': 'The species labeled \\'sR_IL6\\' in the context provided appears to refer to a soluble receptor for interleukin-6 (IL-6), often denoted as sIL-6R. Soluble IL-6 receptors play a crucial role in IL-6 trans-signaling pathways, which differ from classical signaling by involving the soluble receptor form (sIL-6R) rather than the membrane-bound IL-6 receptor (IL-6R).\\n\\n### Biological Function:\\n- **Soluble IL-6 Receptor (sIL-6R):** Its primary function is to bind to the cytokine IL-6, forming a complex that can activate cells that do not have membrane-bound IL-6 receptors. This process is known as \"trans-signaling\" and allows for a wider range of cells to respond to IL-6, expanding its biological effects.\\n\\n### Role in Pathways:\\n- **Trans-signaling Pathway:** In trans-signaling, the IL-6/sIL-6R complex associates with the membrane protein gp130, facilitating intracellular signaling cascades such as the JAK/STAT pathway. This activation leads to gene transcription and biological responses in target cells.\\n- **Classical Signaling Pathway:** sIL-6R is involved in sequestering IL-6 in the presence of the regulatory protein sgp130, modulating the signaling capacity by preventing excessive inflammatory signaling.\\n\\n### Interactions with Other Molecules:\\n- **IL-6:** The soluble receptor interacts with IL-6 to initiate trans-signaling.\\n- **gp130:** Binds the IL-6/sIL-6R complex, essential for downstream signal transduction.\\n- **sgp130:** Acts as a natural inhibitor by sequestering IL-6/sIL-6R complexes, dampening potential overactivation of IL-6 signaling.\\n\\n### Importance in the Biological System:\\nIn the context of Crohn\\'s disease and immune regulation, the IL-6/sIL-6R complex plays a critical role. Modulating this pathway can influence disease progression and therapeutic outcomes. Targeting the IL-6/sIL-6R complex could offer promising treatments by adjusting the immune response and inflammation characteristic of the condition.\\n\\nThe context suggests that sIL-6R could be involved in a model for chronic inflammatory conditions, highlighting its significance in promoting or inhibiting inflammation through different signaling pathways. By understanding its interactions and functions, potential strategies can be developed for therapeutic interventions, such as using antibodies to modify its activity.'},\n", + " {'id': 'mwf345ed7a_0622_403c_b816_c8749a2c9ded',\n", + " 'name': 'Ab',\n", + " 'original_name': 'Ab',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': \"Based on the provided documents, there isn't direct and specific information regarding the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded) in the given context. However, based on general knowledge and context clues, 'Ab' likely refers to an antibody, given the reference to serum Ab concentrations and interaction with IL-6 and sIL-6Rα complexes.\\n\\n1. **Biological Function**: Antibodies (Ab) are proteins produced by the immune system that recognize and bind to specific antigens, such as pathogens (viruses, bacteria) or other target molecules. Their primary function is to neutralize these antigens and facilitate their destruction by other immune cells.\\n\\n2. **Role in Pathways**: In the context provided, 'Ab' is involved in targeting the IL-6 and IL-6Rα pathways. This is indicative of its role in modulating inflammatory responses, likely through the inhibition of the IL-6 signaling pathway.\\n\\n3. **Interactions with Other Molecules**: The document mentions the anti-IL-6 Ab dose response and its effects on serum CRP suppression. The interaction specifically involves the binding of the antibody to IL-6 and the IL-6/sIL-6Rα complex, which suggests its use in blocking or reducing the inflammatory signaling mediated by these molecules.\\n\\n4. **Importance in the Biological System**: The blocking or modulation of IL-6 signaling by antibodies plays a significant role in managing inflammatory diseases. The context implies that targeting IL-6 and its receptor complexes can be part of a therapeutic strategy for conditions characterized by excessive inflammation, such as inflammatory bowel diseases.\\n\\nGiven these points, 'Ab' in this context seems to be associated with therapeutic antibodies used to manage inflammation by interfering with specific cytokine pathways, particularly involving IL-6. This type of intervention is crucial in diseases where cytokine signaling contributes to the pathology.\"},\n", + " {'id': 'mw1da111f2_a036_4392_8512_015005bdcbb7',\n", + " 'name': 'Ab_sR',\n", + " 'original_name': 'Ab_sR',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': \"The specific species 'Ab_sR' (ID: mw1da111f2_a036_4392_8512_015005bdcbb7) located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e does not seem to be explicitly mentioned in the provided context. However, based on the context and general knowledge, we can infer some relevant background information about similar biological components that usually appear in such contexts. \\n\\nThe context mentions components such as sIL-6R, IL-6, and their interactions, which are indicative of a role in inflammatory response pathways. sIL-6R is a soluble form of the IL-6 receptor, and it typically participates in what's known as IL-6 trans-signaling. In this process, instead of the membrane-bound receptor, IL-6 binds to sIL-6R to form a complex that can interact with the gp130 protein, initiating signaling cascades even in cells that do not express the full receptor. This mechanism is important in regulating immune responses, inflammation, and possibly chronic inflammatory diseases by influencing the production of acute-phase proteins like C-reactive protein (CRP).\\n\\nGiven this understanding, 'Ab_sR' could potentially refer to an antibody or an interaction factor related to the soluble receptor pathways, possibly playing a regulatory or inhibitory role in these pathways through binding interactions. Its importance might then be deduced from its capability to modulate these signaling pathways, with potential therapeutic implications for diseases driven by excessive IL-6 signaling.\\n\\nIf Ab_sR is an antibody, it could play a role similar to antibodies against IL-6 or IL-6Rα, aiming to disrupt or modify these signaling pathways, potentially reducing inflammatory responses as a therapeutic strategy. Such antibodies are being explored in contexts of autoimmune diseases, cancers, and inflammatory disorders. \\n\\nNote: This inference is made based on the context provided and common biological functions of related components. Further specific information would be required for more accurate detailing of Ab_sR's role.\"},\n", + " {'id': 'mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac',\n", + " 'name': 'Ab_sR_IL6',\n", + " 'original_name': 'Ab_sR_IL6',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': \"The context provided does not directly specify information about a species named 'Ab_sR_IL6'. However, based on general knowledge and the context given, we can make some inferences and provide related information:\\n\\n1. **Biological Function**: Given the naming convention used ('Ab_sR_IL6'), it is likely that this refers to an antibody (Ab) targeting a soluble receptor (sR) for interleukin-6 (IL-6), possibly inhibiting its action. IL-6 is a cytokine involved in inflammatory and immune responses.\\n\\n2. **Role in Pathways**: IL-6 typically signals through its receptor complex, including IL-6R and gp130, to activate downstream signaling pathways like JAK/STAT, leading to the activation of transcription factors such as STAT3. This cascade leads to the expression of various genes involved in inflammation and immune regulation.\\n\\n3. **Interactions with Other Molecules**: Based on the context, the antibody could be interacting with the IL-6/sIL-6R complex to modulate its effects. The text describes interactions involving sIL-6R and IL-6, potentially including competition or inhibition by antibodies that alter the signaling outcomes and inflammatory responses.\\n\\n4. **Importance in the Biological System Being Modeled**: In the context of the model described, inhibiting the IL-6/sIL-6R interaction is a focus, likely due to its role in conditions like Crohn's Disease or rheumatoid arthritis. Modifying this pathway's activity through an antibody such as 'Ab_sR_IL6' might be of therapeutic significance, potentially helping to suppress excessive inflammatory responses, as suggested by the interest in CRP (C-reactive protein) suppression and dose-response relationships.\\n\\nIn summary, 'Ab_sR_IL6' is likely conceptualized as an antibody targeting the soluble IL-6 receptor to interfere with IL-6 mediated signaling pathways, which are pivotal in certain inflammatory diseases. While specific details are not provided in the context, this inference aligns with common therapeutic strategies involving cytokine signaling modulation.\"},\n", + " {'id': 'CRP_Suppression___',\n", + " 'name': 'CRP Suppression (%)',\n", + " 'original_name': 'CRP Suppression (%)',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': 'Based on the context provided, \"CRP Suppression (%)\" refers to the measurement of the reduction in serum C-reactive protein (CRP) levels. CRP is a biological marker of inflammation, and its levels can be indicative of inflammatory responses in the body. Understanding the suppression of CRP levels has the following implications:\\n\\n1. **Biological Function**: CRP is an acute phase protein, produced by the liver in response to inflammation. It plays a role in the body\\'s immune response, indicating tissue damage or inflammation.\\n\\n2. **Role in Pathways**: CRP is involved in the inflammatory pathway. Suppressing CRP levels typically suggests an underlying modulation of the inflammatory response, often facilitated through interventions like antibodies targeting specific inflammatory cytokines or receptors, such as IL-6 or IL-6Rα in this context.\\n\\n3. **Interactions with Other Molecules**: The context implies interactions with Interleukin-6 (IL-6) and its receptor (IL-6Rα). Treatments with anti–IL-6 or anti–IL-6Rα antibodies reduce CRP levels, thereby modulating inflammation, as indicated by the provided data on drug dose and CRP suppression.\\n\\n4. **Importance in the Biological System**: Suppression of serum CRP is an important indicator of the efficacy of drugs, like anti-IL-6 or anti-IL-6Rα antibodies, in reducing inflammatory responses. This makes CRP suppression a critical measure for evaluating the outcome of therapeutic interventions aimed at inflammatory diseases.\\n\\nWhile the context does not directly describe CRP Suppression (%) as a biological species, it is a measure of the effectiveness of treatments targeting inflammatory pathways. Interactions that lead to its suppression are essential for understanding therapeutic impacts on inflammation-related conditions.'},\n", + " {'id': 'CRP____of_baseline',\n", + " 'name': 'CRP (% of baseline)',\n", + " 'original_name': 'CRP (% of baseline)',\n", + " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", + " 'background': 'The term \"CRP (% of baseline)\" is referring to C-reactive protein (CRP) levels measured as a percentage of a baseline value. In the context provided, it appears to be a metric used in the modeling and analysis of clinical trial data related to anti–IL-6Rα antibody treatments, specifically tocilizumab, which is an anti-inflammatory medication. Here\\'s a summary based on the context and general knowledge about CRP:\\n\\n1. **Biological Function:**\\n - CRP is a protein produced by the liver in response to inflammation. It is part of the acute phase response to inflammation and is a biomarker commonly used to assess inflammation and tissue injury.\\n\\n2. **Role in Pathways:**\\n - CRP is a key player in the acute inflammatory response and is involved in pathways that react to injury, infection, and inflammation. It interacts with the immune system to facilitate the clearance of necrotic and apoptotic cells and bacteria.\\n\\n3. **Interactions with Other Molecules:**\\n - CRP levels are influenced by the presence of pro-inflammatory cytokines, particularly interleukin-6 (IL-6). This context highlights the interaction between CRP levels and anti–IL-6Rα antibodies, which inhibit IL-6 signaling and therefore can suppress CRP production as part of their therapeutic action.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - In the given context, CRP (% of baseline) serves as an important biomarker for evaluating the efficacy of tocilizumab treatment in suppressing inflammation. The model uses CRP levels to compare and validate simulation results against clinical trial data, indicating its critical role in assessing treatment impacts.\\n\\nNo specific unique details beyond this general framework are detailed in the context, but from a systems biology perspective, CRP measurement is significant for understanding inflammatory processes and the body\\'s response to therapeutic interventions.'},\n", + " {'id': 'mw80848184_e2dd_47ce_86d7_7a21479342bd',\n", + " 'name': 'gp130',\n", + " 'original_name': 'gp130',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"The species named 'gp130' refers to a protein that plays a significant role in the signaling pathway involving interleukin-6 (IL-6) and its receptor. \\n\\n### Biological Function:\\n- **gp130 is a Signal Transducer**: It is primarily a signal-transducing component of the IL-6 receptor complex. It does not bind IL-6 by itself but acts as a signal transducer when associated with IL-6 and IL-6 receptor (IL-6R).\\n\\n### Role in Pathways:\\n- **Interaction with IL-6/IL-6R**: gp130 is crucial in the formation of the signaling complex with IL-6 and its soluble receptor sIL-6R. This complex is central to IL-6 signaling pathways.\\n- **Inhibition of IL-6 Trans-Signaling**: A fusion protein known as sgp130Fc, which combines the extracellular portion of gp130 with an Fc region, has been shown to inhibit IL-6 trans-signaling, demonstrating gp130’s role in regulatory mechanisms.\\n\\n### Interactions with Other Molecules:\\n- **Complex Formation**: It forms a complex with IL-6 and IL-6R, contributing to signal transduction.\\n- **Natural Inhibitor**: Soluble gp130 (sgp130) serves as a natural inhibitor of the IL-6/sIL-6R signaling pathway, preventing excessive signal transduction.\\n\\n### Importance in the Biological System:\\n- **Regulatory Role**: The high baseline level of soluble gp130 (sgp130) in the system acts as a buffering agent against changes in the levels of IL-6/sIL-6R complex, highlighting its regulatory importance.\\n- **Therapeutic Potential**: Therapeutic approaches using sgp130 to target IL-6 signaling pathways, such as in the treatment of Crohn’s disease, underscore its clinical significance.\\n \\nGiven these roles, gp130 is a critical component in the IL-6 signaling pathway and has potential therapeutic implications due to its regulatory capacities in controlling inflammatory responses.\"},\n", + " {'id': 'mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a',\n", + " 'name': 'R_IL6_gp130',\n", + " 'original_name': 'R_IL6_gp130',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"The species named 'R_IL6_gp130', based on its naming and the context provided, likely refers to a complex or interaction involving the cytokine interleukin-6 (IL-6) and the signal transducer glycoprotein 130 (gp130). While the specific document does not provide detailed information about R_IL6_gp130, general knowledge about the IL-6/gp130 interaction helps us understand its potential biological significance.\\n\\n### Biological Function:\\n- **IL-6:** It is a cytokine involved in the regulation of immune responses, inflammation, and hematopoiesis. It plays a crucial role in acute phase responses and is produced at sites of inflammation.\\n- **gp130:** It serves as a signal transducer in the cytokine receptor complex, particularly for the IL-6 family of cytokines. It is involved in several cellular processes, including cell growth and differentiation.\\n\\n### Role in Pathways:\\n- The IL-6/gp130 interaction is central to both classical and trans-signaling pathways. In classical signaling, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), which then associates with gp130 to initiate downstream signaling.\\n- In trans-signaling, IL-6 binds to a soluble form of the IL-6 receptor (sIL-6R), and this complex can then associate with gp130 on the target cell surface, allowing cells that do not express membrane-bound IL-6R to respond to IL-6.\\n\\n### Interactions with Other Molecules:\\n- gp130 is a common subunit shared by several cytokine receptors in the IL-6 family, meaning it participates in a variety of signaling complexes.\\n- The soluble form of gp130 (sgp130) can act as a natural inhibitor by binding to IL-6/sIL-6R complexes and preventing them from interacting with membrane-bound gp130.\\n\\n### Importance in the Biological System Being Modeled:\\n- Given the context of inflammatory diseases such as Crohn’s disease, the IL-6/gp130 axis is likely a critical component in the inflammatory response modulation.\\n- The application of sgp130, or its fusion forms like sgp130Fc, demonstrates the pathway's therapeutic significance as a target for damping excessive IL-6-mediated signaling in inflammatory diseases.\\n\\nIn summary, R_IL6_gp130 refers to a key interaction in the IL-6 signaling pathway, emphasizing its role in inflammatory responses and its potential as a therapeutic target in autoimmune diseases like Crohn's.\"},\n", + " {'id': 'mw4638f126_8cb8_4021_ab41_6ae195743ba0',\n", + " 'name': 'sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", + " 'original_name': 'sR_IL6',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"Based on the provided context and general knowledge, here is the background information on the species 'sR_IL6' with the identifier 'mw4638f126_8cb8_4021_ab41_6ae195743ba0', situated within 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e':\\n\\n1. **Biological Function**: 'sR_IL6' likely refers to the soluble receptor for Interleukin-6 (sIL-6R). Soluble receptors such as sIL-6R can bind to the cytokine IL-6, acting as a co-receptor that allows IL-6 to engage in signaling pathways even in cells that do not express the membrane-bound IL-6 receptor.\\n\\n2. **Role in Pathways**: In the immune system, IL-6 can signal through two main pathways:\\n - **Classical signaling**: IL-6 binds to membrane-bound IL-6R and recruits the gp130 protein to initiate downstream signaling.\\n - **Trans-signaling**: sIL-6R, in complex with IL-6, engages gp130 on cells that do not have the IL-6 receptor, thus expanding the range of cells that can respond to IL-6. This is particularly relevant in inflammatory responses and is studied in contexts such as Crohn's disease.\\n\\n3. **Interactions with Other Molecules**: \\n - sIL-6R forms a complex with IL-6 which can then bind to gp130, leading to activation of downstream signaling pathways such as the JAK/STAT pathway.\\n - sIL-6R can be sequestered by sgp130, a soluble form of gp130, which can regulate the availability of the IL-6/sIL-6R complex for signaling.\\n - C-reactive protein (CRP) is involved in the production of sIL-6R through a process known as CRP-mediated shedding.\\n\\n4. **Importance in the Biological System**: \\n - sIL-6R plays a crucial role in mediating IL-6 trans-signaling, particularly in contexts like chronic inflammation and autoimmune diseases such as Crohn's disease.\\n - The presence of sIL-6R enables IL-6 to exert its effects even in cells lacking direct IL-6 receptors, thereby widening its scope of action within the immune regulatory processes.\\n - Understanding the dynamics of sIL-6R in combination with IL-6 is important for therapeutic considerations, as targeting these complexes can influence pharmacological outcomes in disease states.\\n\\nThus, sR_IL6 (inferred as sIL-6R) is integral to the IL-6 signaling pathways, facilitating broad immunological responses through its role in trans-signaling and interaction with IL-6 and other molecular regulators like sgp130.\"},\n", + " {'id': 'mw10315fa3_6f13_4618_bda8_a8694bd3c374',\n", + " 'name': 'R',\n", + " 'original_name': 'R',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"Given the context provided, the information about the species named 'R' (ID: mw10315fa3_6f13_4618_bda8_a8694bd3c374) is not directly mentioned in the documents. However, we can make inferences based on the information about related molecules and pathways described in the context, particularly those involving IL-6 (interleukin-6) and its receptor.\\n\\n### Inferred Background Information about 'R':\\n\\n1. **Biological Function**:\\n - Since the context discusses IL-6 and its receptors (sIL-6R and IL-6Rα), 'R' could potentially be related to components in the IL-6 signaling pathway. IL-6 is a cytokine involved in inflammation and immune response regulation.\\n\\n2. **Role in Pathways**:\\n - IL-6 interacts with both membrane-bound and soluble forms of its receptor (IL-6R) to initiate downstream signaling cascades, such as the JAK/STAT pathway, which leads to the activation of transcription factors like STAT3 (signal transducer and activator of transcription 3).\\n - The pathway is involved in the transcription of various genes, including those coding for acute-phase proteins like CRP (C-reactive protein), indicating a role in inflammatory processes and liver function.\\n\\n3. **Interactions with Other Molecules**:\\n - IL-6, in combination with its receptor, can activate a signaling complex that involves the JAK proteins and STAT3, influencing gene expression. Soluble forms of the receptor, such as sIL-6R, play a role in trans-signaling, which can modulate responses in cells that do not express the membrane-bound receptor.\\n\\n4. **Importance in the Biological System**:\\n - Given that IL-6 signaling impacts acute-phase response and immune regulation, molecules within this pathway, including 'R' if it is part of this system, are crucial for modulating inflammatory responses. They may be targeted in therapeutic contexts, such as with anti–IL-6 or anti–IL-6Rα therapies, which are indicated in the documents as treatments influencing biomarkers like CRP.\\n\\nIn conclusion, without specific data directly linked to 'R', it can be inferred that 'R' is potentially part of the IL-6 pathway components, involved in immune and inflammatory responses, and plays a significant role in cellular signaling and communication within this biological system.\"},\n", + " {'id': 'mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1',\n", + " 'name': 'IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", + " 'original_name': 'IL6',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"Based on the context provided, the species referred to as 'IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is likely Interleukin-6 (IL-6), a cytokine involved in various biological processes. Here is a summary of relevant background information about IL-6:\\n\\n1. **Biological Function:**\\n - IL-6 is a cytokine that plays a crucial role in immune regulation. It is involved in the inflammatory response and is essential for the body's defense against infections and injuries.\\n\\n2. **Role in Pathways:**\\n - IL-6 signaling can occur through two main pathways:\\n - **Classical Pathway:** This involves the membrane-bound IL-6 receptor (IL-6Rα) where IL-6 binds to IL-6Rα, forming a complex that recruits a membrane-bound gp130 coreceptor, triggering downstream signaling cascades.\\n - **Trans-signaling Pathway:** This involves the soluble IL-6 receptor (sIL-6Rα). The IL-6/sIL-6Rα complex can associate with gp130 to initiate signaling in cells that do not express the membrane-bound IL-6Rα. This pathway is particularly important in inflammatory diseases.\\n\\n3. **Interactions with Other Molecules:**\\n - IL-6 interacts with IL-6Rα and gp130 to form a receptor complex that activates intracellular signaling pathways.\\n - It leads to the phosphorylation of Janus kinase (Jak) family proteins and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3), which are critical for transmitting the signal inside the cell.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - In the context of Crohn's disease, IL-6 contributes to enhanced T-cell survival and resistance to apoptosis in the lamina propria, along with elevated chemokine secretion. This makes it a significant player in the disease's pathology.\\n - The study of IL-6 and its pathways is crucial in understanding its role in diseases such as Crohn's disease and rheumatoid arthritis, and in developing therapeutic interventions targeting IL-6 signaling.\\n\\nOverall, IL-6 is an important cytokine with significant roles in immune response and inflammation, making it a key target for research in immune-mediated diseases.\"},\n", + " {'id': 'mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83',\n", + " 'name': 'R_IL6',\n", + " 'original_name': 'R_IL6',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"Based on the context provided, there is no specific mention of a species named 'R_IL6'. However, based on the context and related molecules mentioned, it is possible to infer some insights into what 'R_IL6' might relate to.\\n\\n### Biological Function:\\n- **IL-6:** IL-6 (Interleukin-6) is a cytokine involved in immune response, inflammation, and hematopoiesis. It plays a significant role in the body's defense mechanisms and is implicated in various diseases when dysregulated.\\n\\n### Role in Pathways:\\n- **IL-6 Signaling Pathway:** This pathway involves the binding of IL-6 to its receptor, IL-6R, and generally leads to the activation of JAK/STAT signaling pathways. This signaling can induce transcription and various immune responses.\\n\\n### Interactions with Other Molecules:\\n- **IL-6R and sIL-6R (soluble IL-6 receptor):** The IL-6 signaling requires the complex formation of IL-6 with its receptor IL-6R, including its soluble form sIL-6R. This complex can further bind to another molecule, gp130 (glycoprotein 130), which is necessary for signal transduction.\\n- **STAT3:** The context mentions pSTAT3 signaling, indicating that IL-6 signaling involves phosphorylation of STAT3, a transcription factor that mediates various gene expressions in response to IL-6.\\n\\n### Importance in the Biological System Being Modeled:\\n- **Regulation and Modeling:** IL-6 is involved in the regulation of immune processes, and its signaling is crucial in understanding conditions like Crohn's disease or rheumatoid arthritis. The context mentions modeling efforts and pharmacokinetic analyses suggesting a focus on IL-6 and its receptor interactions.\\n- **Treatment Implications:** The modeling discussed, such as the dose-response characteristics, indicates IL-6's importance in therapeutic frameworks, potentially focusing on disorders with immune dysregulation.\\n\\n### Potential Inference for 'R_IL6':\\n- While there is no direct mention of 'R_IL6', it could potentially refer to a variant, receptor, or complex of IL-6 involved in signaling pathways. It might be modeled similarly in studies related to immune regulation or therapeutic targeting. Given the context, it is likely associated with IL-6's complex pathways and interactions within the immune system.\\n\\nIn summary, 'R_IL6' could be a component related to IL-6 signaling, likely significant in immune system modeling and therapeutic interventions.\"},\n", + " {'id': 'mw0eb6c959_d408_45a0_a450_928b8c5876bb',\n", + " 'name': 'Ractive',\n", + " 'original_name': 'Ractive',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"The context provided does not include specific information about a species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). However, I can provide inferential information based on the general context described, which involves IL-6 signaling and therapeutic interventions in conditions like rheumatoid arthritis and Crohn’s disease.\\n\\n1. **Biological Function:**\\n - Although 'Ractive' is not directly mentioned, within the context of an immune regulation framework, it could be hypothesized that 'Ractive' might represent a molecule involved in the immune response or signal transduction, perhaps similar to interleukins or receptors.\\n\\n2. **Role in Pathways:**\\n - Considering the IL-6 signaling pathway is a focal point of the study, 'Ractive' might play a role similar to elements of the IL-6 signaling cascade. This could involve participation in cytokine signaling or acting as a receptor or receptor complex, similar to IL-6 or its soluble receptor counterparts.\\n\\n3. **Interactions with Other Molecules:**\\n - 'Ractive' might engage in interactions akin to the IL-6 and its soluble receptor interactions. Such molecules often form complexes that could be potential targets for therapeutic antibodies or other modulators, a common approach in autoimmune conditions like those discussed.\\n\\n4. **Importance in the Biological System:**\\n - If 'Ractive' partakes in a pathway analogous to IL-6 signaling, it could be crucial in mediating inflammatory responses, playing a part in disease progression or resolution, and thus presenting itself as a possible target for therapeutic intervention.\\n\\nWithout specific information on 'Ractive' from the text, these interpretations are speculative and should be considered within the broader context of known signaling pathways and therapeutic targets discussed in the study.\"},\n", + " {'id': 'mw42054cd7_17af_46da_970c_7f99151906ad',\n", + " 'name': 'STAT3',\n", + " 'original_name': 'STAT3',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"Based on the provided context and general knowledge:\\n\\n### Biological Function of STAT3\\nSTAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor activated by phosphorylation. It is a key player in transmitting signals from various cytokines and growth factors to the cell nucleus, where it modifies gene expression. STAT3 is critical for regulating numerous biological processes, including cell growth, apoptosis, and immune response.\\n\\n### Role in Pathways\\nSTAT3 is involved in the JAK-STAT signaling pathway. Upon activation, typically by cytokines such as IL-6, STAT3 is phosphorylated by associated Janus kinases (JAKs), dimerizes, and translocates to the nucleus. In this context, STAT3 appears integral to the IL-6 signaling pathway, which is involved in various cellular responses, including inflammation, immune function, and acute-phase reactions.\\n\\n### Interactions with Other Molecules\\nWithin the IL-6 signaling pathway, STAT3 interacts with molecules such as the IL-6 receptor (IL-6R), gp130, and soluble forms of these receptors (sIL-6R and sgp130). The phosphorylation of STAT3 (pSTAT3) indicates its activation and subsequent transcriptional regulation of target genes.\\n\\n### Importance in Biological Systems\\nSTAT3 plays a significant role in mediating the effects of cytokines like IL-6, which are crucial in immune responses and inflammation. The context mentions disease models such as Crohn's disease, where increased activation of STAT3 (pSTAT3) in tissues is noted, highlighting its potential role in the disease's inflammatory processes. This suggests that STAT3's regulation is pivotal in understanding and developing therapeutic approaches for immune and inflammatory disorders.\\n\\nIn summary, STAT3 is a central molecule in cytokine signaling pathways that influence immune function and inflammation, making it a critical target for studying diseases characterized by dysregulated immune responses, such as Crohn's disease.\"},\n", + " {'id': 'mw39c2e431_fdc3_4964_be29_6ca856620b1b',\n", + " 'name': 'pSTAT3',\n", + " 'original_name': 'pSTAT3',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': 'The context provided mainly revolves around the IL-6 signaling pathway and its components, such as IL-6Rα, gp130, sIL-6Rα, sgp130, and CRP, with sporadic mentions of STAT3 and pSTAT3. Here’s a summary focused on pSTAT3 based on the document and broader biological knowledge:\\n\\n### pSTAT3 Biological Function\\n- **pSTAT3** refers to the phosphorylated form of STAT3 (Signal Transducer and Activator of Transcription 3).\\n- STAT3 is a transcription factor activated in response to cytokines like IL-6.\\n- When phosphorylated, STAT3 dimerizes and translocates to the nucleus to regulate the expression of target genes.\\n\\n### Role in Pathways\\n- **IL-6 Signaling**: pSTAT3 is a critical component of the IL-6 signaling pathway. The binding of IL-6 to its receptor leads to the activation of the JAK kinases, which in turn phosphorylate STAT3.\\n- **Gene Expression**: pSTAT3 influences the transcription of various genes involved in immune responses, cell survival, and proliferation.\\n\\n### Interactions with Other Molecules\\n- **IL-6 and sIL-6Rα**: The context describes the significance of trans-signaling mediated by IL-6 and its soluble receptor forms, which lead to STAT3 phosphorylation.\\n- **gp130**: This coreceptor is crucial for the activation of STAT3. It binds the IL-6/sIL-6R complex leading to STAT3 phosphorylation.\\n- **CRP and other gene products**: The activation of STAT3 can influence the expression of C-reactive protein and other acute-phase proteins.\\n\\n### Importance in the Biological System\\n- **Pathological Conditions**: The document mentions increased pSTAT3 levels in colon biopsies in the context of Crohn’s disease, suggesting its role in inflammatory bowel diseases.\\n- **Biological Significance**: Being a part of the IL-6 signaling pathway, pSTAT3 is important in mediating immune responses and might have implications in various diseases due to dysregulated cytokine signaling.\\n\\nIn summary, pSTAT3 is a pivotal signaling molecule involved in transcriptional regulation, primarily within the IL-6-mediated pathway. Its phosphorylation status determines its activity, which can impact various biological processes and contributes to disease states such as inflammatory bowel disease.'},\n", + " {'id': 'mwd5313618_89eb_4c8c_bc82_66f10f966349',\n", + " 'name': 'CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", + " 'original_name': 'CRP',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': 'The species referred to as \"CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\" in the provided context likely represents C-reactive protein (CRP), based on the common abbreviation for C-reactive protein. Here is a summary of the relevant background information regarding CRP:\\n\\n1. **Biological Function:**\\n - CRP is an acute-phase protein produced by the liver in response to inflammation. Its primary function is to bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system via C1q.\\n\\n2. **Role in Pathways:**\\n - CRP is often used as a clinical biomarker for inflammation. It plays a significant role in the pathway of immune response, particularly in recognizing and promoting the clearance of pathogens and damaged cells, thereby serving as a marker of inflammation and immune system activation.\\n - In the context of the simulation model discussed, changes in CRP levels can indicate the effectiveness of drug treatments targeting the IL-6 signaling pathway, as CRP levels are a downstream effect of cytokine signaling, particularly IL-6.\\n\\n3. **Interactions with Other Molecules:**\\n - CRP interacts with various components of the immune system such as the complement system. It works closely with interleukin-6 (IL-6), as IL-6 is a major inducer of CRP synthesis in the liver.\\n - The context mentions interactions with drugs such as anti-IL-6Rα antibodies, which suggests that CRP levels are used to measure the impact of these treatments on inflammation levels in diseases like Crohn\\'s disease.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - Within the modeled system (as described in the context), CRP serves as a critical marker for inflammation, allowing researchers to predict the impact of various treatment strategies on inflammatory diseases like Crohn\\'s disease.\\n - The model’s ability to predict changes in CRP levels helps in studying the effects of perturbations through different therapeutic approaches aimed at inhibiting the IL-6 signaling pathway.\\n\\nOverall, CRP is an important indicator of inflammation and is crucial in the validation and assessment of disease models involving inflammatory processes, such as those involving IL-6 signaling.'},\n", + " {'id': 'mw2e464cf3_a09c_4b7c_9f3c_06720016a48e',\n", + " 'name': 'sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", + " 'original_name': 'sR',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"Based on the provided context, specific information about the species 'sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned. However, inferring from the general context of the documents, which involve molecular interactions and pathways related to the IL-6 signaling system, the following insights can be suggested:\\n\\n1. **Biological Function**:\\n - The 'sR' component is likely a part of the IL-6 signaling pathway. In similar contexts, 'sR' often denotes soluble receptors. Soluble receptors can modulate the activity of their respective cytokines or hormones by binding to them and altering their bioavailability or impacting downstream signaling pathways.\\n\\n2. **Role in Pathways**:\\n - Considering the IL-6 pathway is mentioned, the 'sR' species might function in the classical signaling or trans-signaling pathways of IL-6. In these pathways, soluble receptors either enhance or inhibit signal transduction, impacting gene expression mediated by factors like STAT3.\\n\\n3. **Interactions with Other Molecules**:\\n - The context suggests interaction with the IL-6 cytokine, as soluble IL-6 receptors (e.g., sIL-6R) bind IL-6, forming a complex (IL-6:sR) that may interact with other receptor components, such as gp130, to elicit a cellular response. These interactions are crucial for regulating inflammatory responses and immune function.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n - Soluble receptors are significant in maintaining homeostasis and regulating the intensity of cytokine signaling. The modeling aspect suggests that understanding the dynamic balance of these components (like sgp130, mentioned in the document) is crucial for accurately predicting system behavior under various conditions and treatments, especially targeting IL-6 or its receptors.\\n\\nIn summary, 'sR' in this context is likely a soluble receptor involved in the IL-6 signaling pathway, influencing immune responses by modulating cytokine availability and activity.\"},\n", + " {'id': 'mw36ea78c1_ed71_4def_96d3_857a442d7195',\n", + " 'name': 'CRPExtracellular',\n", + " 'original_name': 'CRPExtracellular',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"The species named 'CRPExtracellular' likely refers to the extracellular form of C-reactive protein (CRP), a well-known biomarker and acute-phase protein in various biological systems, particularly in the context of inflammation.\\n\\n### Biological Function\\nC-reactive protein (CRP) is produced by the liver in response to inflammation. It is an acute-phase protein that plays a critical role in the host's defense mechanism. CRP is part of the innate immune system as it binds to the surface of dead or dying cells and certain bacteria to activate the complement system, promoting phagocytosis by macrophages.\\n\\n### Role in Pathways\\nIn the context of the provided documents, CRP is linked to the IL-6 signaling pathway. IL-6 is a cytokine that stimulates the production of CRP in the liver. The IL-6 mediated pathway contributes to inflammatory responses, and CRP serves as a downstream marker for inflammation. The model mentioned explores strategies to treat Crohn's disease by inhibiting IL-6 signaling, which suggests a modulation of CRP levels.\\n\\n### Interactions with Other Molecules\\nCRP interacts with various molecules and systems in the body:\\n- It binds to phosphocholine on the surface of dead cells and some types of bacteria.\\n- CRP activates the complement system, which enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells.\\n- CRP levels are used to assess the extent of inflammation in response to stimuli like IL-6, another cytokine involved in the body's inflammatory response.\\n\\n### Importance in the Biological System Being Modeled\\nIn the biological model presented in the documents, CRP serves as a critical biomarker to evaluate the efficacy of therapeutic strategies targeting IL-6 signaling in inflammatory diseases like Crohn's disease. The documents emphasize the model's capacity to predict the response of CRP levels to different treatment strategies, validating the trained model against clinical trial data. Suppression of CRP is an indicator of effective inhibition of inflammation, showcasing the importance of CRP measurement in assessing the success of interventions aimed at controlling inflammatory pathways.\\n\\nIn summary, CRPExtracellular represents the extracellular C-reactive protein operating as a biomarker for inflammation, influenced by IL-6 signaling pathways, and significant in evaluating treatment efficacy for diseases characterized by chronic inflammation.\"},\n", + " {'id': 'mw147d30ec_478e_4090_b496_128a131d29eb',\n", + " 'name': 'sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", + " 'original_name': 'sgp130',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"The species referred to as 'sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' appears to be a protein known as sgp130 located in a specific biological context (ID: mw147d30ec_478e_4090_b496_128a131d29eb). Here is a summary of the relevant background information:\\n\\n1. **Biological Function**: \\n sgp130 is a soluble form of gp130, which is a component of the IL-6 receptor complex. sgp130 acts by binding to the IL-6/sIL-6Rα complex, thereby inhibiting IL-6 trans-signaling. This function is crucial as IL-6 trans-signaling is associated with various inflammatory and autoimmune conditions.\\n\\n2. **Role in Pathways**:\\n sgp130 plays a role in the IL-6 signaling pathway by inhibiting the formation of active signaling complexes. This modulation of the pathway can potentially reduce inflammatory responses mediated through IL-6 trans-signaling.\\n\\n3. **Interactions with Other Molecules**:\\n sgp130 interacts specifically with the complex formed by IL-6 and its soluble receptor sIL-6Rα. By binding to this complex, sgp130 prevents the subsequent interaction with the membrane-bound gp130, effectively blocking signal transduction.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n In the context of therapeutic applications, particularly for conditions such as Crohn's disease, sgp130 is evaluated for its potential use in inhibiting inflammatory signaling. Despite being present in large concentrations compared to IL-6, sensitivity analyses suggest that the therapeutic effectiveness of sgp130-based interventions may require very high doses due to its minimal impact on overall system dynamics at typical concentrations. This is because sgp130 naturally exists in excess relative to IL-6, limiting its impact when used in moderate amounts.\\n\\n5. **Relevance in Systems Biology Model**:\\n The systems biology model suggests that while sgp130 has a role, its overall impact on key output parameters (such as CRP levels) is limited unless used in substantial amounts. It highlights the need for potentially better therapeutic targets like IL-6 and sIL-6Rα, where alterations could more significantly affect system outputs.\\n\\nOverall, sgp130 serves a regulatory function in IL-6 mediated signaling, highlighting its role in inflammatory pathways but with suggested limitations for therapeutic application based on the systems biology model being considered.\"},\n", + " {'id': 'mwab41493c_6349_45f1_a226_3030cfed0e06',\n", + " 'name': 'sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", + " 'original_name': 'sR_IL6_sgp130',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"Based on the provided context, the species 'sR_IL6_sgp130', identified by the ID mwab41493c_6349_45f1_a226_3030cfed0e06, appears to be related to a fusion protein that plays a role in inhibiting IL-6 trans-signaling pathways. This fusion protein, popularly referred to as sgp130Fc, combines the extracellular portion of glycoprotein 130 (gp130) with the Fc region of human IgG1. \\n\\n**Biological Function:**\\nsR_IL6_sgp130 acts to bind specifically to the IL-6/sIL-6Rα complex, which is pivotal in mediating IL-6 trans-signaling. By binding to this complex, it effectively prevents the signaling process that would typically activate downstream pathways, such as the phosphorylation of STAT3 (pSTAT3) and subsequent gene transcription.\\n\\n**Role in Pathways:**\\nIts primary role resides in the inhibition of IL-6 trans-signaling, which is critical in the context of inflammatory responses and diseases like Crohn’s disease. The simulations and models cited suggest that this species is involved in modifying the dose-response relationship of certain therapeutic interventions, leading to outcomes like CRP suppression.\\n\\n**Interactions with Other Molecules:**\\nsR_IL6_sgp130 interacts predominantly with the IL-6/sIL-6Rα complex. The sgp130 component has a high affinity for this complex, which is a major interaction through which it achieves its inhibitory functions.\\n\\n**Importance in the Biological System Being Modeled:**\\nIn the system, while sR_IL6_sgp130 is present in high baseline levels and exerts limited effects on steady-state system dynamics due to its excess relative to free IL-6 concentrations, it remains a pivotal molecule for therapeutic applications. Its primary importance lies in its use as a potential therapeutic intervention, especially considered for conditions with elevated IL-6 trans-signaling, requiring very high and frequent doses to be effective due to its baseline levels.\\n\\nThis summary indicates that sR_IL6_sgp130 is critical in the context of therapies aiming to modulate IL-6 signaling pathways, providing insights into the need for precise dosing strategies to achieve therapeutic benefits.\"},\n", + " {'id': 'mwf405687b_7401_44ec_a0d6_4a2b35c13e8a',\n", + " 'name': 'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", + " 'original_name': 'Ab_sR',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': 'Based on the provided context, no specific information about the species named \\'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\\' was found in the excerpts from the document. However, I can infer some potential characteristics and roles it might have based on general biological knowledge and the information typically associated with similar components.\\n\\n1. **Biological Function**: Generally, \"Ab\" in a biological context often refers to antibodies. If \\'Ab_sR\\' is indeed an antibody or related to antibody activity, its function could be to bind to specific antigens, perhaps part of a signaling pathway or immune response mechanism.\\n\\n2. **Role in Pathways**: The context mentions IL-6 and its receptor interactions, which are part of immune signaling pathways. If \\'Ab_sR\\' is interacting with such pathways, it could be modulating or inhibiting specific signals, particularly in inflammatory or immune responses.\\n\\n3. **Interactions with Other Molecules**: As the context heavily references IL-6, IL-6R, and associated signaling components like STAT3 and SOCS, it is plausible that \\'Ab_sR\\' could interact with these molecules. It might bind to a receptor or signaling molecule to alter its activity.\\n\\n4. **Importance in the Biological System**: Assuming \\'Ab_sR\\' is an antibody related to receptor activity, it could be crucial in modulating inflammatory responses or other cytokine-related pathways. In systems biology models, such antibodies are often used to simulate therapeutic interventions, inhibiting specific pathways to predict changes in disease states or therapeutic outcomes.\\n\\nWithout explicit details from the document, these inferences remain general and speculative. Further details would be needed for precise characterization.'},\n", + " {'id': 'mw3667a5e1_02c9_44a0_acb4_b0431faa822d',\n", + " 'name': 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", + " 'original_name': 'Ab',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"Based on the context provided, there isn't directly available specific information about the species named 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, we can infer its role based on general knowledge and the content present in the documents.\\n\\n1. **Biological Function:** 'Ab' likely refers to an antibody, given the context of medical and pharmacological studies. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects, such as bacteria and viruses.\\n\\n2. **Role in Pathways:** Antibodies are a crucial part of the immune response, often engaging in pathways related to immune regulation and inflammatory responses. Specifically, within the context, it seems to be involved in pathways targeting IL-6 or IL-6Rα, which are significant in inflammatory processes and immune system signaling, especially in conditions like inflammatory bowel diseases and other inflammatory responses.\\n\\n3. **Interactions with Other Molecules:** Within the context, the antibodies interact with IL-6 and sIL-6Rα (soluble IL-6 receptor alpha). These interactions are essential as they form complexes that are targets for therapeutic interventions to suppress inflammatory markers like C-reactive protein (CRP). The effectiveness of such interventions can vary based on whether IL-6 and its receptor are targeted individually or together.\\n\\n4. **Importance in the Biological System:** Antibodies, like the one inferred (potentially anti-IL-6 or similar), are important in modulating the immune response and are used in therapeutic settings to treat diseases where cytokine activity (like that of IL-6) is dysregulated. They help reduce undesirable inflammation and are thus a critical part of managing inflammatory diseases.\\n\\nIn summary, while specific details about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' are not provided, it is most likely a therapeutic antibody involved in pathways targeting IL-6 and its receptor, pivotal in controlling inflammation within biological systems.\"},\n", + " {'id': 'mw772cbf20_3fc1_4800_ae59_77884f1ae333',\n", + " 'name': 'Ab_R',\n", + " 'original_name': 'Ab_R',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"The document provided does not explicitly mention the species 'Ab_R' with the ID 'mw772cbf20_3fc1_4800_ae59_77884f1ae333.' Therefore, I will infer what 'Ab_R' might pertain to based on the general knowledge presented in the context and common biological components.\\n\\n1. **Biological Function:**\\n - Given that the context mentions anti-IL-6 and anti-IL-6Rα antibodies, it is plausible that 'Ab_R' could represent an antibody (Ab) related to these immune system components. \\n\\n2. **Role in Pathways:**\\n - Antibodies targeting the IL-6/IL-6Rα pathway are involved in modulating inflammatory responses. IL-6 is a cytokine involved in immune regulation, and its receptor, IL-6Rα, can exist in both a soluble and membrane-bound form, playing roles in signaling cascades that promote inflammation.\\n\\n3. **Interactions with Other Molecules:**\\n - If 'Ab_R' is, in fact, an antibody similar to anti-IL-6 or anti-IL-6Rα, it would likely bind to these targets to inhibit cytokine signaling, thereby reducing inflammation. It may interact with IL-6, IL-6Rα, or both.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - The context of the document suggests a focus on modeling pharmacokinetics and pharmacodynamics (PK/PD) of antibodies targeting IL-6/IL-6Rα pathways, often to evaluate potential therapeutic interventions for conditions involving chronic inflammation, such as autoimmune diseases or inflammatory diseases like Crohn’s disease (CD).\\n - Such antibodies can serve as therapeutic agents to suppress the inflammatory response by antagonizing the IL-6 pathway, therefore reducing downstream effects like C-reactive protein (CRP) levels, which is a marker of inflammation.\\n\\nConclusively, while the document does not provide direct information on 'Ab_R,' it is likely aligned with therapeutic antibodies targeting cytokine signaling pathways to control inflammation within a modeled biological framework.\"},\n", + " {'id': 'mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf',\n", + " 'name': 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", + " 'original_name': 'Ab_sR_IL6',\n", + " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", + " 'background': \"The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned in the provided context. However, it is possible to infer details about this species based on the context and general knowledge about similar biological components, such as sIL-6R and IL-6.\\n\\n1. **Biological Function**: \\n - Since 'Ab_sR_IL6' likely refers to an antibody (Ab) targeting soluble IL-6 receptor (sIL-6R), its primary function would be to bind soluble IL-6R, potentially inhibiting its interaction with IL-6.\\n\\n2. **Role in Pathways**:\\n - In immune regulation pathways, particularly those involving interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R) can form complexes with IL-6 to mediate signaling even in cells that do not express membrane-bound IL-6R. By targeting sIL-6R, the antibody could disrupt these signaling cascades, serving as a potential therapeutic strategy in diseases characterized by excessive IL-6 signaling, such as rheumatoid arthritis or Crohn’s disease.\\n\\n3. **Interactions with Other Molecules**:\\n - Ab_sR_IL6 would primarily interact with sIL-6R, preventing it from binding to IL-6. This could impede the formation of the IL-6/sIL-6R complex, potentially reducing downstream signaling through the STAT3 pathway and other associated responses, such as C-reactive protein (CRP) production in the liver.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n - In the context of a model focused on immune regulation, particularly in conditions like Crohn’s disease, targeting sIL-6R with an antibody could be critical in modulating the inflammatory response. By acting on the IL-6 signaling pathway, such an approach could help manage systemic inflammation and related symptoms.\\n\\nWhile there is no specific mention of 'Ab_sR_IL6' in the provided documents, understanding its potential role can be inferred based on known dynamics of IL-6, sIL-6R, and their involvement in immune and inflammatory processes.\"},\n", + " {'id': 'mw7becb5fe_8da8_4285_a821_0d77ad811b62',\n", + " 'name': 'sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", + " 'original_name': 'sR_IL6',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the provided context, there is no specific mention or detailed description of a species or molecule named 'sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, we can infer information about its potential biological role based on general knowledge of similar components in the context of the document, which discusses IL-6 signaling pathways.\\n\\nThe document prominently features IL-6 (Interleukin-6) and its role in the context of immune regulation, particularly in relation to Crohn’s disease. IL-6 is a cytokine involved in inflammation and immune responses. It signals through two main pathways: classical signaling and trans-signaling. In classical signaling, IL-6 binds to its membrane-bound receptor, IL-6R, and subsequently recruits gp130, leading to the activation of downstream pathways such as the JAK/STAT pathway. In trans-signaling, IL-6 can also bind to a soluble form of its receptor, sIL-6R, allowing it to act on cells that do not express membrane-bound IL-6R.\\n\\nGiven the emphasis on IL-6 and sIL-6R in the context, 'sR_IL6' could refer to a soluble receptor or a related soluble component in the IL-6 signaling pathway. This type of molecule typically facilitates trans-signaling interactions. It may interact with IL-6 to form a complex that can then engage with another component, sgp130, to modulate signaling. This complex plays a role in regulating immune responses and could have therapeutic implications, especially in diseases like Crohn’s disease where IL-6 signaling is dysregulated.\\n\\nIn summary, if 'sR_IL6' is indeed related to IL-6 signaling, its biological importance might lie in modulating inflammatory responses through trans-signaling, interacting with IL-6 and possibly other soluble receptors or signaling molecules in this pathway. Its role would be crucial in maintaining homeostasis in immune function and could be a target for therapeutic interventions.\"},\n", + " {'id': 'mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca',\n", + " 'name': 'gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", + " 'original_name': 'gp130',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the provided context, here is the summarized background information about the gp130 species:\\n\\n1. **Biological Function**: gp130 is a protein that plays a critical role in signaling pathways, specifically as part of the interleukin-6 (IL-6) signaling pathway. It acts as a key signal transducer and is involved in the formation of a signaling complex with the IL-6 receptor.\\n\\n2. **Role in Pathways**: gp130 is an integral component of the signaling complex formed between IL-6 and its soluble receptor, sIL-6Rα. The complex formation is crucial for IL-6 trans-signaling, which is implicated in various inflammatory responses.\\n\\n3. **Interactions with Other Molecules**: gp130 interacts with IL-6 and sIL-6Rα to form a hexameric complex that is necessary for initiating the downstream signaling cascade. Soluble gp130 (sgp130) acts as a natural inhibitor by binding to this complex, thereby preventing trans-signaling.\\n\\n4. **Importance in the Biological System**: In the context of the system being modeled, soluble gp130 (sgp130) is considered a potential therapeutic agent, especially in conditions like Crohn's disease, due to its ability to inhibit IL-6 trans-signaling. However, the effectiveness of sgp130 is dependent on achieving high and frequent doses, as small alterations in sgp130 levels have minimal impact due to its high baseline concentration relative to IL-6.\\n\\nOverall, gp130 is pivotal for IL-6-mediated signaling, and modifications in its activity can potentially modulate inflammatory pathways, making it a significant target in certain therapeutic approaches.\"},\n", + " {'id': 'mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9',\n", + " 'name': 'R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", + " 'original_name': 'R_IL6_gp130',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the context provided, the species named 'R_IL6_gp130' appears to relate to the interleukin-6 (IL-6) signaling pathway, which involves the interaction of IL-6 with its receptor components for signal transduction. Although specific details about this species are not directly provided in the context, we can infer its characteristics and role based on the general knowledge of similar biological components involved in IL-6 signaling:\\n\\n1. **Biological Function**: R_IL6_gp130 likely represents a complex involving IL-6, its specific receptor, and the signal transducer gp130. In the IL-6 signaling pathway, gp130 serves as a critical signal transducer that, upon activation by the IL-6/IL-6 receptor complex, initiates intracellular signaling cascades that influence gene expression.\\n\\n2. **Role in Pathways**: This species is part of the IL-6 signaling pathway, which can activate the JAK/STAT signaling cascade, resulting in the phosphorylation of STAT3 (Signal Transducer and Activator of Transcription 3). This pathway is crucial in mediating inflammatory responses and plays a role in various physiological and pathological processes, including immune regulation, inflammation, and cell growth.\\n\\n3. **Interactions with Other Molecules**: R_IL6_gp130 likely interacts with IL-6 and its soluble receptor (sIL-6R), as well as with gp130. This interaction forms a complex that facilitates signal transduction through the gp130 component, leading to downstream effects such as the activation of STAT3. It can also interact with inhibitors like soluble gp130 (sgp130) or fusion proteins designed to modulate this signaling pathway.\\n\\n4. **Importance in the Biological System**: Within the context described, R_IL6_gp130 is important for understanding the dynamics of IL-6 signaling, especially in inflammatory conditions such as Crohn's disease. The IL-6 pathway is targeted for therapeutic intervention, suggesting its significance in disease pathology and treatment.\\n\\nIn summary, R_IL6_gp130 likely represents a key component of the IL-6 signaling pathway, central to mediating the effects of IL-6 through gp130 in inflammation and immune response, as inferred from the general function of similar complexes.\"},\n", + " {'id': 'mw6cce2109_0e32_4dd9_98ec_41173e8ef07d',\n", + " 'name': 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", + " 'original_name': 'Ractive',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the provided context, there appears to be no specific information about the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' within the text. However, the context discusses the IL-6 signaling pathway and its components, particularly focusing on the interactions between IL-6, sIL-6Rα, and therapeutic antibodies, such as the humanized anti-interleukin 6 receptor antibody (tocilizumab). This suggests a theme centered around immune response regulation, specifically in diseases like rheumatoid arthritis and possibly Crohn's disease.\\n\\nIn the absence of specific information about 'Ractive', we can infer its potential role based on the discussed biological components. It is likely that 'Ractive' could be involved in the pathways related to cytokine signaling, immune modulation, or therapeutic interactions similar to those of IL-6 or its receptor complex. Its importance in the system may be linked to modulating immune responses or serving as a target or mediator in therapeutic approaches within the context of the mentioned diseases.\\n\\nIn systems biology modeling, species or molecules like 'Ractive' could be critical for either transmitting signals within a pathway, modifying the activity of other molecules, or acting as a checkpoint or target for drugs designed to alter biological responses in conditions like Crohn's disease or rheumatoid arthritis.\"},\n", + " {'id': 'mw2b255f94_8018_4b99_bde8_918eeac45446',\n", + " 'name': 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", + " 'original_name': 'STAT3',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the provided context, the species 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is likely referring to the well-known protein STAT3, a signal transducer and activator of transcription 3. Here is the relevant background information about STAT3:\\n\\n1. **Biological Function**:\\n - STAT3 is involved in the phosphorylation process as part of cell signaling. Phosphorylated STAT3 (pSTAT3) is indicative of its active state, which can translocate to the nucleus to act as a transcription factor.\\n - It plays a crucial role in relaying signals from cytokine receptors, like the IL-6 receptor complex, to the nucleus, influencing gene expression.\\n\\n2. **Role in Pathways**:\\n - STAT3 is a central component of the JAK-STAT signaling pathway. Once activated, it typically mediates the effects of cytokines, such as IL-6, contributing to various cellular responses, including growth, differentiation, and survival.\\n - The context mentions its involvement in pathways activated by IL-6, a cytokine that triggers immune responses, inflammation, and acute-phase reactions.\\n\\n3. **Interactions with Other Molecules**:\\n - STAT3 gets activated by cytokines binding to their respective receptors, leading to JAK kinases' activation, which subsequently phosphorylates STAT3.\\n - It interacts with components of the IL-6 receptor family, specifically affecting the pathways involving IL-6 trans-signaling.\\n - The context also suggests interactions involving sIL-6R (a soluble IL-6 receptor) and sgp130 (a soluble form of the co-receptor gp130), where pSTAT3 acts in various compartments like the GI tract and liver depending on cytokine signaling.\\n\\n4. **Importance in the Biological System**:\\n - STAT3 is important in modeling biological systems that involve immune responses or inflammation, such as in the context of Crohn's disease, as indicated by increased pSTAT3 levels in serum and tissues affected by the disease.\\n - Its role as a transcription factor makes it key in regulating downstream gene expression that could contribute to disease pathology and the body's response to inflammation.\\n\\nIn summary, although there is no direct mention of a species specifically labeled 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' in the document, the general characteristics and functions of STAT3 can be inferred based on common scientific knowledge and the provided context about IL-6 signaling and related pathways.\"},\n", + " {'id': 'mw48867e93_f170_44e8_ac7a_185b23e1bf3b',\n", + " 'name': 'pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", + " 'original_name': 'pSTAT3',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the context provided, specific information about the biological species 'pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is not explicitly detailed. However, we can infer its role and significance based on the general knowledge about pSTAT3 and its involvement in biological processes.\\n\\n1. **Biological Function:**\\n - pSTAT3, or phosphorylated STAT3, is a form of Signal Transducer and Activator of Transcription 3 (STAT3) that becomes activated through phosphorylation. This activation enables pSTAT3 to translocate to the cell nucleus, where it functions as a transcription factor, promoting the expression of various genes involved in cell growth, survival, and differentiation.\\n\\n2. **Role in Pathways:**\\n - In the context described, pSTAT3 is associated with IL-6 signaling, which involves classical and trans-signaling pathways. IL-6 is a cytokine involved in immune response, and its interaction with receptors such as IL-6R and gp130 leads to the activation of JAK kinases and subsequent phosphorylation of STAT3 (pSTAT3). This signaling cascade is crucial in mediating responses to inflammation and stress.\\n\\n3. **Interactions with Other Molecules:**\\n - pSTAT3 interacts with the IL-6 receptor complex, including sIL-6R (soluble IL-6 receptor) and sgp130 (soluble gp130). The complex formation and subsequent signaling facilitate various downstream effects. pSTAT3 is known to regulate the expression of suppressor of cytokine signaling (SOCS) proteins and other gene products involved in modulating immune responses.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - pSTAT3 plays a critical role in inflammatory responses, as highlighted by its reported increase in serum concentrations in conditions like Crohn’s disease. It is involved in the transcriptional regulation of acute-phase proteins such as C-reactive protein (CRP) and other gene products that are significant in the immune response and inflammation within the gastrointestinal tract and liver.\\n\\nThis inferred information helps underscore the importance of pSTAT3 in immune modulation and its potential implications in inflammatory diseases, even though specific details about its ID-specific characteristics in the context were not provided.\"},\n", + " {'id': 'mw0083d743_836f_4238_a17f_4602193d5bc0',\n", + " 'name': 'geneProduct',\n", + " 'original_name': 'geneProduct',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"The provided context from the document does not include specific details about the biological species or molecule identified as 'geneProduct' with the ID: mw0083d743_836f_4238_a17f_4602193d5bc0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. There is no explicit mention of this molecule's biological function, role in pathways, interactions with other molecules, or its importance in the biological system being modeled.\\n\\nBased on the context, which predominantly discusses interleukin-6 (IL-6) pathways, receptors, and related molecules (e.g., sIL-6R, gp130, and sgp130), we can infer that 'geneProduct' might be related to the IL-6 signaling pathway or another signaling molecule involved in inflammatory or immune responses. In systems biologically concerned with inflammation or cytokine signaling, such gene products might typically be involved in cell signaling cascades, playing roles in activating transcription factors, interacting with receptors or co-receptors, and affecting the expression of downstream genes important for cellular responses.\\n\\nSince specific data is not available, hypothetical pathways could involve roles similar to those of IL-6 or its receptors—modulating inflammatory responses, and participating in acute phase reactions, including CRP production in the liver. Gene products in such pathways often interact with other cytokines, receptors, and intracellular signaling proteins to exert their effects, potentially influencing processes like cell proliferation, differentiation, and survival.\"},\n", + " {'id': 'mwd31f52cc_04e7_40e0_885f_c7b2d9e62215',\n", + " 'name': 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", + " 'original_name': 'sR',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the context provided, there is no explicit mention of the species 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' directly in the excerpts. However, we can infer some related information using general knowledge and by examining the related components and interactions in the context shared.\\n\\nThe context revolves around the interaction and dynamics involving the Interleukin-6 (IL-6) signaling pathway, soluble IL-6 receptor (sIL-6R), and the involvement of other molecules like sgp130. \\n\\n### Inferred Background Information about 'sR':\\n\\n1. **Biological Function:**\\n - In the context of cytokine signaling, receptors like sR are generally involved in recognizing and binding to specific signaling molecules (e.g., cytokines such as IL-6) to facilitate their biological functions. Therefore, 'sR' could act as a receptor or part of a receptor complex in signaling pathways.\\n\\n2. **Role in Pathways:**\\n - Given the presence of IL-6 and its receptor dynamics (e.g., IL-6/sIL-6R complex) in the context, 'sR' might participate in cytokine signaling pathways, potentially serving as a modulator that enhances or inhibits signal transduction depending on its specific interactions with IL-6 or other pathway components like sgp130.\\n\\n3. **Interactions with Other Molecules:**\\n - The sIL-6R forms complexes with IL-6, which then interact with membrane-bound receptors to initiate signaling cascades like the activation of STAT3. 'sR' might potentially interact similarly, indicating a critical role in modifying the intensity or outcome of the signaling process.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - The balance of soluble receptors and cytokines (such as IL-6/sIL-6R) and their interactions with other molecules (e.g., sgp130) are essential for controlling inflammatory responses and other downstream effects (e.g., CRP production in the liver).\\n - Given this, 'sR' could play a pivotal regulatory role, affecting the system's sensitivity to changes in cytokine levels and potentially serving as a target for therapeutic interventions.\\n\\n### Conclusion:\\n\\nWhile the provided document excerpts do not explicitly detail 'sR's identity or function, its inferred associations with key players like IL-6, sIL-6R, and sgp130 suggest a role in cytokine signaling modulation, particularly in pathways relevant to inflammation and immune response. For specific molecular functions and pathway roles, further examination of full-length documents or additional sources would be required.\"},\n", + " {'id': 'mw2c9b0499_3325_4394_8af3_bbf653a944a0',\n", + " 'name': 'IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", + " 'original_name': 'IL6',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the provided context and general knowledge, the species named 'IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' is likely referring to Interleukin-6 (IL-6), a cytokine involved in various biological functions and pathways. Here is a summary of its roles and significance:\\n\\n1. **Biological Function:**\\n - IL-6 is a multifunctional cytokine that plays a critical role in immune response regulation, inflammation, and hematopoiesis.\\n - It is known to be a mediator of fever and of the acute phase response.\\n\\n2. **Role in Pathways:**\\n - IL-6 signaling occurs via two main pathways: the classical signaling pathway and the trans-signaling pathway.\\n - The classical pathway involves IL-6 binding to a membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of IL-6Rα (sIL-6Rα).\\n - Both pathways converge on a signal transduction cascade that activates Janus kinase (Jak) proteins and leads to the phosphorylation of signal transducer and activator of transcription 3 (STAT3).\\n\\n3. **Interactions with Other Molecules:**\\n - IL-6 interacts with its receptor IL-6Rα (either membrane-bound or soluble) and forms a complex that recruits the gp130 coreceptor.\\n - This interaction is crucial for activating downstream signaling pathways that are involved in immune responses.\\n\\n4. **Importance in the Biological System:**\\n - IL-6 is particularly important in inflammatory diseases such as Crohn's disease, where it contributes to enhanced T-cell survival and resistance to apoptosis in the intestinal mucosa, as well as elevated chemokine secretion.\\n - It plays a significant role in the pathophysiology of autoimmune diseases and chronic inflammatory conditions, making it a target for therapeutic interventions such as with specific antibodies like tocilizumab.\\n\\nIn summary, IL-6 is a central cytokine in immune regulation and inflammatory processes, which makes it a pivotal part of the biological system being modeled, particularly in the context of diseases like Crohn's disease.\"},\n", + " {'id': 'mwd65b5b39_dc1b_4e77_a999_67277a880e5e',\n", + " 'name': 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", + " 'original_name': 'sgp130',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the provided context, here is the background information about the species 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)':\\n\\n### Biological Function:\\nsgp130, known here as a species variant, reflects a biological molecule related to the inhibition of IL-6 trans-signaling. It specifically refers to a fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is designed to inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex.\\n\\n### Role in Pathways:\\nsgp130 plays a role in pathways involving the interleukin-6 (IL-6) signaling cascade. It specifically targets the IL-6/sIL-6Rα complex, blocking the trans-signaling pathway that can contribute to inflammatory responses, such as those observed in Crohn’s disease.\\n\\n### Interactions with Other Molecules:\\nsgp130 interacts with the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc binds this complex with the same affinity as natural sgp130, thus inhibiting the signaling pathways mediated by IL-6.\\n\\n### Importance in the Biological System:\\nsgp130 appears to be of limited effect in altering the steady-state values of certain biomarkers unless present in large quantities. It exists in excess compared to free IL-6, leading to minimal effect from small perturbations in its levels. Hence, any significant observable effects require substantial changes in sgp130 concentrations.\\n\\nDespite its biological function, the context suggests that sgp130-based therapeutic strategies may not be as robust as anticipated. The sensitivity analysis indicated that the output biomarkers are less affected by sgp130 levels, making IL-6 and sIL-6Rα more potent targets for intervention in the studied system. This contributes to understanding its therapeutic potential limitations, particularly in addressing diseases like Crohn's where IL-6 signaling is implicated.\"},\n", + " {'id': 'mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3',\n", + " 'name': 'sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", + " 'original_name': 'sR_IL6_sgp130',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': 'The species sR_IL6_sgp130, identified as mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 within the context provided, appears to involve components related to interleukin-6 (IL-6) signaling pathways. Here is the summary of the background based on the given context and general knowledge:\\n\\n### Biological Function\\n- **Fusion Protein**: The document mentions a fusion protein involving sgp130, which combines the extracellular portion of the gp130 protein with the Fc region of human IgG1. This fusion protein, known as sgp130Fc, is designed to inhibit IL-6 trans-signaling in cells.\\n\\n### Role in Pathways\\n- **IL-6 Trans-Signaling**: The primary role of sgp130Fc is to inhibit IL-6 trans-signaling. In the IL-6 signaling pathway, IL-6 can signal through its receptor complex involving IL-6R and gp130, leading to downstream effects such as the activation of STAT3 transcription factors. The fusion protein acts to prevent this signaling pathway by binding to the IL-6/sIL-6Rα complex.\\n- **Simulations in Crohn’s Disease**: The sgp130Fc protein is being studied for its therapeutic potential in inflammatory conditions like Crohn’s disease, where IL-6 signaling plays a significant role.\\n\\n### Interactions with Other Molecules\\n- **Binding with IL-6/sIL-6Rα Complex**: The sgp130Fc is assumed to bind with the IL-6/sIL-6Rα complex with affinities similar to natural sgp130. The presence of sgp130Fc in large quantities suggests it primarily functions by excess binding to this complex, thereby preventing excessive IL-6 signaling.\\n\\n### Importance in the Biological System\\n- **Therapeutic Potential**: The document outlines the use of sgp130Fc as a potential therapeutic intervention in diseases with aberrant IL-6 signaling, such as Crohn’s disease. It has been shown to only be effective at very high doses due to its interaction landscape.\\n- **Limited Systemic Impact**: Due to high baseline levels of sgp130 compared to IL-6, small changes in sgp130 do not significantly affect the system, implying its role predominantly emerges under conditions requiring high-dose applications or alterations.\\n\\nOverall, while the document primarily discusses the use of a related molecule (sgp130Fc), it emphasizes the relevance of sgp130 interactions within IL-6-related pathways, underscoring its importance in modulating immune and inflammatory responses within certain pathological contexts.'},\n", + " {'id': 'mwf7796221_1fea_4274_a93e_c00adbf5778c',\n", + " 'name': 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", + " 'original_name': 'Ab',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the provided context, there is no specific detailed information available about the species or molecule 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' with the ID mwf7796221_1fea_4274_a93e_c00adbf5778c. However, from the context and general knowledge, we can infer the following:\\n\\n1. **Biological Function**: The document references serum antibody (Ab) concentrations in nmol/l, which suggests that 'Ab' likely stands for an antibody. Antibodies are proteins produced by the immune system to identify and neutralize pathogens such as bacteria and viruses.\\n\\n2. **Role in Pathways**: The context mentions anti-IL-6/sIL-6Rα interactions. Antibodies targeting the interleukin-6 (IL-6) pathway are typically used in treatments to modulate immune responses, particularly in inflammatory conditions. They can bind to IL-6 or its receptor to inhibit the downstream signaling pathway.\\n\\n3. **Interactions with Other Molecules**: The document discusses the anti-IL-6 Ab's effect in relation to IL-6 and sIL-6Rα. This suggests that the antibody in question interacts specifically with these cytokines or cytokine receptors, playing a role in reducing inflammation by interfering with the IL-6 signaling pathway.\\n\\n4. **Importance in the Biological System**: The antibody’s importance seems to be related to its therapeutic role in modulating the immune response, particularly in diseases involving heavy inflammation. This can include conditions like inflammatory bowel diseases or other autoimmune disorders, where targeting IL-6 or its receptor can have significant therapeutic effects.\\n\\nIn summary, based on the context and typical characteristics of antibodies in similar biological systems, 'Ab' is likely an antibody involved in targeting the IL-6 signaling pathway, important for managing inflammatory responses in various conditions.\"},\n", + " {'id': 'mw5d764bb8_5693_4ac8_9557_f65992cc5eb0',\n", + " 'name': 'Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", + " 'original_name': 'Ab_sR',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"Based on the provided context, there is no specific mention or details about the species named 'Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, I can infer potential roles and functions based on adjacent biological components and typical interactions within such systems, especially considering the discussion around IL-6 pathways and related molecules in the context.\\n\\n1. **Biological Function**: In this particular study context, sIL-6R (soluble Interleukin-6 receptor) and IL-6 (a cytokine involved in inflammation and immune responses) are key components. Ab_sR might refer to an antibody-related soluble receptor component or variant. If related to IL-6/sIL-6R pathways, its function could involve modulation of immune responses or inflammation via binding interactions.\\n\\n2. **Role in Pathways**: The surrounding context heavily discusses the interaction of IL-6 with its receptor and the subsequent signaling pathways, such as the Jak-STAT pathway (notably leading to STAT3 activation), indicating a role in cytokine-receptor interactions. Ab_sR could interact within these pathways, perhaps as an intermediary or a modulator influencing signal transduction.\\n\\n3. **Interactions with Other Molecules**: If analogous to sIL-6R or anti-IL-6 therapeutic antibodies, Ab_sR might interact with IL-6, potentially modulating its effects by altered binding dynamics or competitive inhibition. Such interactions could influence downstream signaling events leading to transcriptional changes (e.g., expression of SOCS or CRP).\\n\\n4. **Importance in Biological System Being Modeled**: In systems modeling inflammatory responses, any component similar to an antibody interacting with cytokines like IL-6 is critical. It could predictively simulate treatment outcomes for inflammatory diseases or evaluate drug efficacy (e.g., CRP suppression in inflammatory cases). Ab_sR may hold similar significance if it's part of experimental or theoretical models assessing cytokine network modulation.\\n\\nWhile these are educated guesses based on typical roles and interactions of analogous proteins within such biological systems, exact functions and roles of Ab_sR would be best determined by specifics from the cited source text.\"},\n", + " {'id': 'mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2',\n", + " 'name': 'Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", + " 'original_name': 'Ab_sR_IL6',\n", + " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", + " 'background': \"The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2) does not have specific background information provided explicitly in the context you shared. However, I can infer potential characteristics based on general knowledge about similar components.\\n\\n### Inferred Background Information:\\n\\n1. **Biological Function:**\\n - 'Ab_sR_IL6' likely refers to an antibody ('Ab') targeting the soluble form of the interleukin-6 receptor (sIL-6R). This suggests it is involved in neutralizing or modulating the biological effects of sIL-6R, potentially inhibiting its interaction with interleukin-6 (IL-6).\\n\\n2. **Role in Pathways:**\\n - The context described the targeting of the IL-6/sIL-6R complex as a treatment strategy for conditions involving excessive IL-6 signaling, such as Crohn's disease. 'Ab_sR_IL6' might play a role in suppressing IL-6-mediated pathways, thereby reducing inflammation or immune responses associated with diseases like Crohn's disease or rheumatoid arthritis.\\n\\n3. **Interactions with Other Molecules:**\\n - Interacts with sIL-6R, preventing the formation of the IL-6/sIL-6R complex. This interaction would diminish the activity of the classical and trans-signaling pathways mediated by IL-6, leading to reduced activation of downstream signaling molecules like STAT3 and associated gene transcription.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - Its importance lies in modulating inflammation by impacting IL-6 signaling. As IL-6 is crucial in immune response modulation, controlling its activity can lead to therapeutic benefits in diseases characterized by inflammation and immune dysregulation.\\n\\nBroadly, 'Ab_sR_IL6' serves as a critical component in therapeutic models aiming to attenuate aberrant IL-6 signaling pathways in immune-mediated diseases.\"},\n", + " {'id': 'mwbc2f5464_81e5_43fd_8b39_f5a2756af72f',\n", + " 'name': 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)',\n", + " 'original_name': 'Ab',\n", + " 'compartment': 'mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87',\n", + " 'background': \"The provided context does not contain direct information specifically about the species 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, from the available information, we can infer some details based on the general context and related biological components mentioned:\\n\\n1. **Biological Function**: The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects like bacteria and viruses. They play a crucial role in targeting specific antigens for the immune response.\\n\\n2. **Role in Pathways**: The context discusses the interaction between anti-IL-6 antibodies and IL-6/sIL-6Rα complex. IL-6 is a cytokine involved in inflammation and infection responses. Hence, antibodies targeting IL-6 pathways are often part of therapeutic interventions for inflammatory diseases.\\n\\n3. **Interactions with Other Molecules**: The document mentions the targeting of IL-6 and IL-6/sIL-6Rα complexes, suggesting that this antibody interacts with these molecules, likely inhibiting their function to reduce inflammation as indicated by the suppression of CRP (C-reactive protein), a marker of inflammation.\\n\\n4. **Importance in the Biological System Being Modeled**: The antibody's role appears to be significant in modulating inflammatory responses by targeting key molecular pathways involving IL-6 and its receptors. This indicates its potential therapeutic value in treating conditions where IL-6 is implicated, such as autoimmune or inflammatory diseases.\\n\\nIn summary, while the antibody 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)' is not directly described in the context, inferred information suggests it likely functions as an IL-6 pathway inhibitor in an inflammatory response model, emphasizing its role in treatment strategies aimed at modulating immune responses.\"}]" ] }, "execution_count": 9, @@ -361,24 +1949,24 @@ "text/plain": [ "['Crohns disease',\n", " 'IL-6',\n", - " 'T-cells',\n", - " 'apoptosis',\n", - " 'inflammation',\n", - " 'IL-6Rα',\n", - " 'sIL-6Rα',\n", + " 'IL-6R',\n", + " 'sIL-6R',\n", + " 'CRP',\n", " 'gp130',\n", " 'Jak',\n", " 'STAT3',\n", - " 'CRP',\n", + " 'T-cells',\n", " 'hepatocytes',\n", - " 'leukocytes',\n", + " 'apoptosis',\n", + " 'inflammation',\n", + " 'GI tract',\n", " 'sgp130',\n", " 'tocilizumab',\n", - " 'GI tract',\n", - " 'liver',\n", - " 'monoclonal antibodies',\n", - " 'SOCS',\n", - " 'circulation']" + " 'cytokines',\n", + " 'Janus kinase',\n", + " 'lamina propria',\n", + " 'leukocytes',\n", + " 'chemokine']" ] }, "execution_count": 10, From 8f9fc7297cecfd2bea4ecc176716acc0dcffe93f Mon Sep 17 00:00:00 2001 From: ShengZhaoDE Date: Fri, 7 Mar 2025 13:30:46 +0100 Subject: [PATCH 11/14] update results files --- notebook/pdf_keywords.txt | 2 +- notebook/sbml_rag_notebook.ipynb | 1187 +++++++++++++++--------------- notebook/species_backgrounds.csv | 839 ++++++++++----------- 3 files changed, 1019 insertions(+), 1009 deletions(-) diff --git a/notebook/pdf_keywords.txt b/notebook/pdf_keywords.txt index 353054ab..8f8d0ee2 100644 --- a/notebook/pdf_keywords.txt +++ b/notebook/pdf_keywords.txt @@ -1 +1 @@ -Crohns disease, IL-6, IL-6R, sIL-6R, CRP, gp130, Jak, STAT3, T-cells, hepatocytes, apoptosis, inflammation, GI tract, sgp130, tocilizumab, cytokines, Janus kinase, lamina propria, leukocytes, chemokine \ No newline at end of file +Crohns disease, IL-6, IL-6Rα, sIL-6Rα, gp130, STAT3, pSTAT3, Jak, CRP, tocilizumab, T-cells, hepatocytes, lymphocytes, apoptosis, inflammation, chemokine, acute-phase proteins, monoclonal antibodies, sgp130, Jak-STAT \ No newline at end of file diff --git a/notebook/sbml_rag_notebook.ipynb b/notebook/sbml_rag_notebook.ipynb index 554a3483..75fd808d 100644 --- a/notebook/sbml_rag_notebook.ipynb +++ b/notebook/sbml_rag_notebook.ipynb @@ -30,7 +30,7 @@ "outputs": [], "source": [ "# Uncomment to install required packages if not already installed\n", - "# !pip install langchain langchain-openai langchain-community faiss-cpu python-libsbml pypdf" + "# !pip install langchain langchain-openai langchain-community faiss-cpu python-libsbml pypdf " ] }, { @@ -189,24 +189,24 @@ "PDF Keywords:\n", "1. Crohns disease\n", "2. IL-6\n", - "3. IL-6R\n", - "4. sIL-6R\n", - "5. CRP\n", - "6. gp130\n", - "7. Jak\n", - "8. STAT3\n", - "9. T-cells\n", - "10. hepatocytes\n", - "11. apoptosis\n", - "12. inflammation\n", - "13. GI tract\n", - "14. sgp130\n", - "15. tocilizumab\n", - "16. cytokines\n", - "17. Janus kinase\n", - "18. lamina propria\n", - "19. leukocytes\n", - "20. chemokine\n" + "3. IL-6Rα\n", + "4. sIL-6Rα\n", + "5. gp130\n", + "6. STAT3\n", + "7. pSTAT3\n", + "8. Jak\n", + "9. CRP\n", + "10. tocilizumab\n", + "11. T-cells\n", + "12. hepatocytes\n", + "13. lymphocytes\n", + "14. apoptosis\n", + "15. inflammation\n", + "16. chemokine\n", + "17. acute-phase proteins\n", + "18. monoclonal antibodies\n", + "19. sgp130\n", + "20. Jak-STAT\n" ] } ], @@ -263,7 +263,7 @@ " IL6\n", " IL6\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " The provided context outlines the biological f...\n", + " Based on the provided context, IL6 (Interleuki...\n", " \n", " \n", " 1\n", @@ -271,7 +271,7 @@ " sgp130\n", " sgp130\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " Based on the context provided, sgp130 is a bio...\n", + " The species 'sgp130' appears to be related to ...\n", " \n", " \n", " 2\n", @@ -279,7 +279,7 @@ " sR_IL6_sgp130\n", " sR_IL6_sgp130\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " Based on the provided context from the documen...\n", + " The species 'sR_IL6_sgp130' appears to be invo...\n", " \n", " \n", " 3\n", @@ -287,7 +287,7 @@ " CRP\n", " CRP\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " The term 'CRP' within the context provided ref...\n", + " C-reactive protein (CRP) is a crucial protein ...\n", " \n", " \n", " 4\n", @@ -295,7 +295,7 @@ " sR\n", " sR\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " Based on the provided context, the species nam...\n", + " Based on the provided context, there is limite...\n", " \n", " \n", " 5\n", @@ -303,7 +303,7 @@ " sR_IL6\n", " sR_IL6\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " The species labeled 'sR_IL6' in the context pr...\n", + " The species \"sR_IL6,\" identified by the ID mw0...\n", " \n", " \n", " 6\n", @@ -311,7 +311,7 @@ " Ab\n", " Ab\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " Based on the provided documents, there isn't d...\n", + " Based on the provided context from the documen...\n", " \n", " \n", " 7\n", @@ -319,7 +319,7 @@ " Ab_sR\n", " Ab_sR\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " The specific species 'Ab_sR' (ID: mw1da111f2_a...\n", + " Based on the provided context, specific inform...\n", " \n", " \n", " 8\n", @@ -327,7 +327,7 @@ " Ab_sR_IL6\n", " Ab_sR_IL6\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " The context provided does not directly specify...\n", + " Based on the context provided, there is no spe...\n", " \n", " \n", " 9\n", @@ -335,7 +335,7 @@ " CRP Suppression (%)\n", " CRP Suppression (%)\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " Based on the context provided, \"CRP Suppressio...\n", + " CRP Suppression (%) refers to the extent to wh...\n", " \n", " \n", " 10\n", @@ -343,7 +343,7 @@ " CRP (% of baseline)\n", " CRP (% of baseline)\n", " mw53ffe9e6_beef_45c4_90a5_a79197ed506e\n", - " The term \"CRP (% of baseline)\" is referring to...\n", + " Based on the context provided and general know...\n", " \n", " \n", " 11\n", @@ -351,7 +351,7 @@ " gp130\n", " gp130\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " The species named 'gp130' refers to a protein ...\n", + " Based on the provided context, the biological ...\n", " \n", " \n", " 12\n", @@ -359,7 +359,7 @@ " R_IL6_gp130\n", " R_IL6_gp130\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " The species named 'R_IL6_gp130', based on its ...\n", + " Based on the context and general knowledge abo...\n", " \n", " \n", " 13\n", @@ -367,7 +367,7 @@ " sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e...\n", " sR_IL6\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " Based on the provided context and general know...\n", + " The molecule in question, sR_IL6 (mw88ca8d9a_f...\n", " \n", " \n", " 14\n", @@ -375,7 +375,7 @@ " R\n", " R\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " Given the context provided, the information ab...\n", + " The provided context refers to interactions an...\n", " \n", " \n", " 15\n", @@ -383,7 +383,7 @@ " IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", " IL6\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " Based on the context provided, the species ref...\n", + " Based on the context provided and general know...\n", " \n", " \n", " 16\n", @@ -391,7 +391,7 @@ " R_IL6\n", " R_IL6\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " Based on the context provided, there is no spe...\n", + " The provided context does not explicitly detai...\n", " \n", " \n", " 17\n", @@ -399,7 +399,7 @@ " Ractive\n", " Ractive\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " The context provided does not include specific...\n", + " The provided context does not contain specific...\n", " \n", " \n", " 18\n", @@ -415,7 +415,7 @@ " pSTAT3\n", " pSTAT3\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " The context provided mainly revolves around th...\n", + " Based on the provided context and general know...\n", " \n", " \n", " 20\n", @@ -423,7 +423,7 @@ " CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", " CRP\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " The species referred to as \"CRP (mw88ca8d9a_f5...\n", + " Based on the context provided, here is the bac...\n", " \n", " \n", " 21\n", @@ -431,7 +431,7 @@ " sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", " sR\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " Based on the provided context, specific inform...\n", + " From the context provided, it seems that the s...\n", " \n", " \n", " 22\n", @@ -439,7 +439,7 @@ " CRPExtracellular\n", " CRPExtracellular\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " The species named 'CRPExtracellular' likely re...\n", + " Based on the provided context, it seems that s...\n", " \n", " \n", " 23\n", @@ -447,7 +447,7 @@ " sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e...\n", " sgp130\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " The species referred to as 'sgp130 (mw88ca8d9a...\n", + " Based on the provided context, the species lab...\n", " \n", " \n", " 24\n", @@ -455,7 +455,7 @@ " sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f...\n", " sR_IL6_sgp130\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " Based on the provided context, the species 'sR...\n", + " Based on the context provided, specific mentio...\n", " \n", " \n", " 25\n", @@ -463,7 +463,7 @@ " Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,...\n", " Ab_sR\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " Based on the provided context, no specific inf...\n", + " The context provided does not contain specific...\n", " \n", " \n", " 26\n", @@ -471,7 +471,7 @@ " Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\n", " Ab\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " Based on the context provided, there isn't dir...\n", + " The context provided does not offer any specif...\n", " \n", " \n", " 27\n", @@ -479,7 +479,7 @@ " Ab_R\n", " Ab_R\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " The document provided does not explicitly ment...\n", + " The context provided does not specifically men...\n", " \n", " \n", " 28\n", @@ -487,7 +487,7 @@ " Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a...\n", " Ab_sR_IL6\n", " mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e\n", - " The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9...\n", + " The provided context lacks specific informatio...\n", " \n", " \n", " 29\n", @@ -495,7 +495,7 @@ " sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5...\n", " sR_IL6\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the provided context, there is no spe...\n", + " The species 'sR_IL6' (ID: mw7becb5fe_8da8_4285...\n", " \n", " \n", " 30\n", @@ -503,7 +503,7 @@ " gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,...\n", " gp130\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the provided context, here is the sum...\n", + " Based on the provided context, the species 'gp...\n", " \n", " \n", " 31\n", @@ -511,7 +511,7 @@ " R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fc...\n", " R_IL6_gp130\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the context provided, the species nam...\n", + " Based on the context and information provided,...\n", " \n", " \n", " 32\n", @@ -519,7 +519,7 @@ " Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b...\n", " Ractive\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the provided context, there appears t...\n", + " The provided context does not directly referen...\n", " \n", " \n", " 33\n", @@ -527,7 +527,7 @@ " STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,...\n", " STAT3\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the provided context, the species 'ST...\n", + " Based on the available context from the provid...\n", " \n", " \n", " 34\n", @@ -535,7 +535,7 @@ " pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5...\n", " pSTAT3\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the context provided, specific inform...\n", + " The provided context does not contain detailed...\n", " \n", " \n", " 35\n", @@ -543,7 +543,7 @@ " geneProduct\n", " geneProduct\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " The provided context from the document does no...\n", + " The provided context does not specifically des...\n", " \n", " \n", " 36\n", @@ -551,7 +551,7 @@ " sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", " sR\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the context provided, there is no exp...\n", + " Based on the provided context, there is specif...\n", " \n", " \n", " 37\n", @@ -559,7 +559,7 @@ " IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", " IL6\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the provided context and general know...\n", + " Based on the provided context, IL-6 (likely re...\n", " \n", " \n", " 38\n", @@ -567,7 +567,7 @@ " sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5...\n", " sgp130\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the provided context, here is the bac...\n", + " The species or molecule 'sgp130 (mwe9501423_9f...\n", " \n", " \n", " 39\n", @@ -575,7 +575,7 @@ " sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3...\n", " sR_IL6_sgp130\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " The species sR_IL6_sgp130, identified as mw633...\n", + " Based on the context provided, there is no spe...\n", " \n", " \n", " 40\n", @@ -583,7 +583,7 @@ " Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\n", " Ab\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the provided context, there is no spe...\n", + " Based on the provided context, there is no dir...\n", " \n", " \n", " 41\n", @@ -591,7 +591,7 @@ " Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,...\n", " Ab_sR\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " Based on the provided context, there is no spe...\n", + " The context provided does not include any spec...\n", " \n", " \n", " 42\n", @@ -599,7 +599,7 @@ " Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb1...\n", " Ab_sR_IL6\n", " mwe9501423_9fb4_494b_b5b6_288f3fcb17b5\n", - " The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4...\n", + " Based on the provided context, there is no spe...\n", " \n", " \n", " 43\n", @@ -607,7 +607,7 @@ " Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)\n", " Ab\n", " mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87\n", - " The provided context does not contain direct i...\n", + " The provided context does not explicitly menti...\n", " \n", " \n", "\n", @@ -753,50 +753,50 @@ "43 mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87 \n", "\n", " background \n", - "0 The provided context outlines the biological f... \n", - "1 Based on the context provided, sgp130 is a bio... \n", - "2 Based on the provided context from the documen... \n", - "3 The term 'CRP' within the context provided ref... \n", - "4 Based on the provided context, the species nam... \n", - "5 The species labeled 'sR_IL6' in the context pr... \n", - "6 Based on the provided documents, there isn't d... \n", - "7 The specific species 'Ab_sR' (ID: mw1da111f2_a... \n", - "8 The context provided does not directly specify... \n", - "9 Based on the context provided, \"CRP Suppressio... \n", - "10 The term \"CRP (% of baseline)\" is referring to... \n", - "11 The species named 'gp130' refers to a protein ... \n", - "12 The species named 'R_IL6_gp130', based on its ... \n", - "13 Based on the provided context and general know... \n", - "14 Given the context provided, the information ab... \n", - "15 Based on the context provided, the species ref... \n", - "16 Based on the context provided, there is no spe... \n", - "17 The context provided does not include specific... \n", + "0 Based on the provided context, IL6 (Interleuki... \n", + "1 The species 'sgp130' appears to be related to ... \n", + "2 The species 'sR_IL6_sgp130' appears to be invo... \n", + "3 C-reactive protein (CRP) is a crucial protein ... \n", + "4 Based on the provided context, there is limite... \n", + "5 The species \"sR_IL6,\" identified by the ID mw0... \n", + "6 Based on the provided context from the documen... \n", + "7 Based on the provided context, specific inform... \n", + "8 Based on the context provided, there is no spe... \n", + "9 CRP Suppression (%) refers to the extent to wh... \n", + "10 Based on the context provided and general know... \n", + "11 Based on the provided context, the biological ... \n", + "12 Based on the context and general knowledge abo... \n", + "13 The molecule in question, sR_IL6 (mw88ca8d9a_f... \n", + "14 The provided context refers to interactions an... \n", + "15 Based on the context provided and general know... \n", + "16 The provided context does not explicitly detai... \n", + "17 The provided context does not contain specific... \n", "18 Based on the provided context and general know... \n", - "19 The context provided mainly revolves around th... \n", - "20 The species referred to as \"CRP (mw88ca8d9a_f5... \n", - "21 Based on the provided context, specific inform... \n", - "22 The species named 'CRPExtracellular' likely re... \n", - "23 The species referred to as 'sgp130 (mw88ca8d9a... \n", - "24 Based on the provided context, the species 'sR... \n", - "25 Based on the provided context, no specific inf... \n", - "26 Based on the context provided, there isn't dir... \n", - "27 The document provided does not explicitly ment... \n", - "28 The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9... \n", - "29 Based on the provided context, there is no spe... \n", - "30 Based on the provided context, here is the sum... \n", - "31 Based on the context provided, the species nam... \n", - "32 Based on the provided context, there appears t... \n", - "33 Based on the provided context, the species 'ST... \n", - "34 Based on the context provided, specific inform... \n", - "35 The provided context from the document does no... \n", - "36 Based on the context provided, there is no exp... \n", - "37 Based on the provided context and general know... \n", - "38 Based on the provided context, here is the bac... \n", - "39 The species sR_IL6_sgp130, identified as mw633... \n", - "40 Based on the provided context, there is no spe... \n", - "41 Based on the provided context, there is no spe... \n", - "42 The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4... \n", - "43 The provided context does not contain direct i... " + "19 Based on the provided context and general know... \n", + "20 Based on the context provided, here is the bac... \n", + "21 From the context provided, it seems that the s... \n", + "22 Based on the provided context, it seems that s... \n", + "23 Based on the provided context, the species lab... \n", + "24 Based on the context provided, specific mentio... \n", + "25 The context provided does not contain specific... \n", + "26 The context provided does not offer any specif... \n", + "27 The context provided does not specifically men... \n", + "28 The provided context lacks specific informatio... \n", + "29 The species 'sR_IL6' (ID: mw7becb5fe_8da8_4285... \n", + "30 Based on the provided context, the species 'gp... \n", + "31 Based on the context and information provided,... \n", + "32 The provided context does not directly referen... \n", + "33 Based on the available context from the provid... \n", + "34 The provided context does not contain detailed... \n", + "35 The provided context does not specifically des... \n", + "36 Based on the provided context, there is specif... \n", + "37 Based on the provided context, IL-6 (likely re... \n", + "38 The species or molecule 'sgp130 (mwe9501423_9f... \n", + "39 Based on the context provided, there is no spe... \n", + "40 Based on the provided context, there is no dir... \n", + "41 The context provided does not include any spec... \n", + "42 Based on the provided context, there is no spe... \n", + "43 The provided context does not explicitly menti... " ] }, "execution_count": 6, @@ -830,825 +830,830 @@ "================================================================================\n", "1. IL6 (ID: mwf626e95e_543f_41e4_aad4_c6bf60ab345b)\n", "================================================================================\n", - "The provided context outlines the biological function and role of IL-6, a cytokine important in the immune system. Based on the information:\n", - "\n", - "1. **Biological Function**:\n", - " IL-6 is a cytokine involved in immune regulation. It plays a crucial role in enhancing T-cell survival and resistance to apoptosis, particularly in the context of Crohn’s Disease, as well as in promoting chemokine secretion.\n", + "Based on the provided context, IL6 (Interleukin 6) is a cytokine that plays a crucial role in immune regulation, particularly in the context of inflammatory conditions such as Crohn's disease and rheumatoid arthritis. \n", "\n", - "2. **Role in Pathways**:\n", - " IL-6 signaling can proceed via two distinct pathways:\n", - " - The classical pathway, which involves the membrane-bound IL-6 receptor (IL-6Rα).\n", - " - The trans-signaling pathway, which involves a soluble IL-6 receptor (sIL-6Rα). In both pathways, IL-6 forms a complex with its respective receptor, which then recruits the gp130 coreceptor, leading to the formation of a hexameric receptor complex. This complex initiates phosphorylation of gp130-bound Janus kinase (Jak) proteins and subsequent activation of STAT3 (Signal Transducer and Activator of Transcription 3).\n", + "### Biological Function:\n", + "IL6 is involved in immune responses and inflammation. It contributes significantly to the survival of T-cells and confers resistance to apoptosis in the lamina propria, a layer of the intestinal mucosa, thereby playing an important role in the pathology of inflammatory bowel diseases like Crohn's disease. It is also associated with elevated chemokine secretion.\n", "\n", - "3. **Interactions with Other Molecules**:\n", - " IL-6 interacts with its membrane-bound and soluble receptors to initiate signaling. The interaction sequence involves IL-6 binding to IL-6Rα, recruiting gp130, and activating downstream signaling molecules like Jak family proteins and STAT3.\n", + "### Role in Pathways:\n", + "IL6 signaling can occur through two main pathways:\n", + "1. **Classical Pathway**: This involves the membrane-bound IL-6 receptor (IL-6Rα). In this process, IL6 binds to IL-6Rα on the cell membrane, forming a complex that recruits the membrane-bound coreceptor gp130, which forms a heterotrimeric complex. This complex dimerizes into a hexameric receptor complex, activating downstream signaling cascades.\n", + "2. **Trans-signaling Pathway**: Here, IL6 binds to a soluble form of IL-6Rα (sIL-6Rα), and this complex also recruits gp130, following a similar mechanism to form an active signaling complex. Trans-signaling is particularly important in pathological conditions where traditional signaling pathways are altered or less efficient.\n", "\n", - "4. **Importance in the Biological System Being Modeled**:\n", - " IL-6 is highlighted as a significant contributor in the pathophysiology of Crohn’s Disease due to its roles in promoting immune cell activities that lead to inflammation. The ability of IL-6 to engage in both classical and trans-signaling pathways suggests it is a versatile mediator in inflammatory processes, making it a critical target for therapeutic interventions.\n", + "### Interactions with Other Molecules:\n", + "IL6 interacts with both membrane-bound and soluble forms of its receptor IL-6Rα to initiate signaling cascades. The activated receptor complex initiates phosphorylation of Janus kinase (Jak) family proteins, which subsequently phosphorylate signal transducer and activator of transcription 3 (STAT3). This signaling cascade is pivotal in mediating the biological effects of IL6 in inflammatory and immune responses. Additionally, the model demonstrates interactions between IL6, its receptors, and therapeutic antibodies like tocilizumab, which are designed to suppress IL6 signaling.\n", "\n", - "5. **General Knowledge and Inference**:\n", - " Beyond the context, IL-6 is generally known to be involved in inflammation and is a key player in various inflammatory diseases. It is a target for drugs like tocilizumab, which inhibit IL-6 signaling by preventing the interaction of IL-6 with its receptor, thus being an important therapeutic strategy in diseases such as rheumatoid arthritis.\n", + "### Importance in the Biological System Being Modeled:\n", + "In the context of Crohn's disease, IL6 is highlighted as a significant mediator of immune regulation, particularly due to its role in enhancing T-cell survival and modulating chemokine secretion, which are key components of the disease's pathology. Targeting IL6 signaling pathways, whether through classical or trans-signaling, could be a therapeutic strategy for managing inflammatory responses associated with Crohn’s disease and similar conditions.\n", "\n", - "In summary, IL-6 is a multifunctional cytokine central to immune regulation and inflammation, making it a crucial element in disease models, particularly those addressing inflammatory conditions like Crohn's Disease.\n", + "In summary, IL6 is a critical cytokine involved in immune regulation and inflammatory signaling, serving as both a potential target for therapeutic intervention and a key player in the pathogenesis of diseases such as Crohn's disease and rheumatoid arthritis.\n", "\n", "================================================================================\n", "2. sgp130 (ID: mwbbbce920_e8dd_4320_9386_fc94bfb2fc99)\n", "================================================================================\n", - "Based on the context provided, sgp130 is a biological molecule that plays a role in inhibiting IL-6 trans-signaling. Here is a summary of its background information:\n", + "The species 'sgp130' appears to be related to a modified version of the gp130 protein, specifically referred to as sgp130Fc. Here is a summary based on the provided context:\n", "\n", - "1. **Biological Function**: sgp130 is derived from the extracellular portion of the gp130 protein. It serves to inhibit the signaling pathway of interleukin-6 (IL-6) by binding to the IL-6/sIL-6Rα complex, thereby preventing it from activating downstream signaling pathways. This inhibition is achieved by a fusion protein called sgp130Fc, which combines sgp130 with the Fc region of human IgG1.\n", + "1. **Biological Function**: sgp130 is primarily involved in inhibiting IL-6 trans-signaling. This is achieved by its ability to bind to the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1, has been shown to inhibit this pathway in cultured cells.\n", "\n", - "2. **Role in Pathways**: sgp130 influences the IL-6 signaling pathway, specifically targeting the trans-signaling aspect. IL-6 is a pro-inflammatory cytokine that can signal through a complex with soluble IL-6 receptor (sIL-6Rα) and gp130. By interfering with this pathway, sgp130 can modulate inflammatory responses.\n", + "2. **Role in Pathways**: The primary pathway of interest involving sgp130 is the IL-6 signaling pathway. IL-6 is a cytokine implicated in various inflammatory processes, and its trans-signaling via the soluble IL-6 receptor (sIL-6Rα) is distinct from classical signaling. The role of sgp130 is to regulate this trans-signaling pathway by competing with cell surface gp130 receptors, thereby reducing the pro-inflammatory effects mediated by IL-6/sIL-6Rα.\n", "\n", - "3. **Interactions with Other Molecules**: The primary interaction of sgp130 is with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 inhibits its ability to signal through the cell surface-bound gp130, thus blocking IL-6 mediated effects. The interaction between sgp130 and the IL-6/sIL-6Rα complex is central to its function.\n", + "3. **Interactions with Other Molecules**: sgp130 interacts with the IL-6/sIL-6Rα complex. In the presence of high amounts of sgp130, most of the IL-6 is bound, thus preventing it from mediating its effects via the trans-signaling pathway.\n", "\n", - "4. **Importance in the Biological System Being Modeled**: While sgp130 can effectively inhibit IL-6 trans-signaling, the context indicates that its role in the system being modeled is limited. The sensitivity analysis within the model shows that alterations in sgp130 levels have minimal effects on the steady-state values of output parameters due to the high baseline level of sgp130 compared to the relatively low concentration of free IL-6. This suggests that sgp130-based therapies may not be as impactful unless used at high and frequent doses. The model under discussion aimed at simulating its potential therapeutic use in conditions like Crohn’s disease.\n", + "4. **Importance in the Biological System**: Despite its potential therapeutic role, the sensitivity analysis from the provided context suggests that sgp130 has a relatively low impact on the steady-state dynamics of the system being modeled. This is attributed to its high baseline concentration compared to IL-6, implying that large changes in sgp130 levels are needed to achieve significant biological effects. Therefore, the efficacy of sgp130-based therapies, like sgp130Fc, may be limited and require high doses to be effective.\n", "\n", - "Overall, sgp130 is important for modulating IL-6 trans-signaling, but in the specific system modeled, its impact is limited under normal conditions due to its already high concentration compared to IL-6.\n", + "Overall, sgp130 serves as a regulatory molecule within the IL-6 signaling pathway, specifically targeting and mitigating the effects of IL-6 trans-signaling, though its standalone therapeutic potential may be limited due to high baseline levels and lower impact on system sensitivity.\n", "\n", "================================================================================\n", "3. sR_IL6_sgp130 (ID: mw810ff751_fa4e_4143_bd50_169b3e325e1e)\n", "================================================================================\n", - "Based on the provided context from the document, 'sR_IL6_sgp130' seems to be a part of the IL-6 signaling pathway and is likely a reference to a complex involving soluble IL-6 receptor components. Here's a summary based on the information provided and general knowledge:\n", + "The species 'sR_IL6_sgp130' appears to be involved in the system of IL-6 signaling, which plays a critical role in inflammatory responses such as those found in diseases like Crohn's disease. Based on the provided context, here's a summary of its background information:\n", "\n", - "- **Biological Function:** The complex is involved in modulating IL-6 signaling, particularly influencing the trans-signaling mechanism. Soluble gp130 (sgp130) acts as a natural inhibitor of IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing it from associating with membrane-bound gp130, which is necessary for signal transduction.\n", + "1. **Biological Function**: sR_IL6_sgp130 is likely related to the IL-6 signaling pathway. It is suggested to be a complex involving soluble IL-6 receptor (sIL-6R) and sgp130, which is a fusion protein comprised of the extracellular portion of the gp130 receptor and the Fc region of human IgG1. The gp130 receptor is part of the signaling pathway for IL-6, a cytokine involved in immune responses.\n", "\n", - "- **Role in Pathways:** It is a critical modulator in the IL-6 signaling pathway. Normally, IL-6 binds to the soluble IL-6 receptor (sIL-6R), and this complex can further engage with gp130 on cell surfaces to propagate downstream signaling events. The sgp130 serves as a sink for these IL-6/sIL-6R complexes, limiting their ability to bind to cellular gp130 and hence reducing downstream signaling such as STAT3 activation.\n", + "2. **Role in Pathways**: sR_IL6_sgp130 is involved in the inhibition of IL-6 trans-signaling. This pathway is crucial for mediating pro-inflammatory responses. The context suggests that sgp130 can bind to the IL-6/sIL-6Rα complex, potentially blocking further signaling within this pathway.\n", "\n", - "- **Interactions with Other Molecules:** The complex interacts primarily with IL-6 and its soluble receptor (sIL-6R). It prevents these molecules from engaging with cell-surface gp130, thus acting as a competitive inhibitor in the pathway.\n", + "3. **Interactions with Other Molecules**: The species interacts with IL-6 and sIL-6Rα. The fusion protein sgp130Fc has been shown to bind to the IL-6/sIL-6Rα complex, suggesting that sR_IL6_sgp130 may act to sequester this complex and prevent it from engaging with cell surface receptors, thereby inhibiting downstream signaling, including pSTAT3 activation.\n", "\n", - "- **Importance in the Biological System:** In the context of the system being modeled, sgp130 is crucial as it regulates the balance of IL-6 signaling. Its high baseline concentration relative to IL-6 suggests it plays a stabilization role in keeping the system responsive only to significant changes in IL-6 levels. However, its effectiveness as a therapeutic agent, such as in Crohn’s disease, may require high and frequent dosing due to its large baseline presence and minimal effect on system dynamics under normal conditions.\n", + "4. **Importance in the Biological System Being Modeled**: Despite its role in inhibiting IL-6 signaling, sensitivity analyses indicate that altering sgp130 levels has a minimal effect on the steady-state dynamics of the system due to its high baseline concentration. This suggests that while sR_IL6_sgp130 has the potential to influence inflammation pathways, its impact may be limited under normal conditions and would require significant changes to yield observable effects. \n", "\n", - "No direct information about 'sR_IL6_sgp130' as a separate distinct entity is found in the context, suggesting it might be inferred from understanding sgp130's complex with IL-6 and sIL-6R within the described signaling and therapeutic contexts.\n", + "Overall, sR_IL6_sgp130 represents an important therapeutic target or molecule within the context of IL-6 mediated diseases, but its natural abundance and resultant low system sensitivity under basal conditions make it a challenging target for effective therapeutic intervention without substantial dosage alterations.\n", "\n", "================================================================================\n", "4. CRP (ID: mw114aa90f_5f5b_4fe8_9406_361c8489b6a1)\n", "================================================================================\n", - "The term 'CRP' within the context provided refers to C-reactive protein, rather than a distinct biological species. C-reactive protein is a well-known biomarker present in the bloodstream, often used to assess inflammation within the body. Here's a summary of relevant background information about CRP based on the context and general biological understanding:\n", + "C-reactive protein (CRP) is a crucial protein in the context of inflammation and immune response regulation. Based on the provided context and general knowledge about CRP, the following summarizes its biological role and significance:\n", "\n", - "- **Biological Function**: C-reactive protein is an acute-phase protein produced by the liver in response to inflammation. Its primary role is to bind to the surface of dead or dying cells (and some types of bacteria) to activate the complement system, thereby promoting phagocytosis by macrophages. This function is part of the body's innate immune response, aiding in clearing pathogens and dead cells from the bloodstream.\n", + "1. **Biological Function**:\n", + " - CRP is an acute-phase protein, primarily produced in the liver in response to inflammation. It is commonly used as a marker to assess inflammatory states in various conditions. The production is typically induced by cytokines such as interleukin-6 (IL-6).\n", "\n", - "- **Role in Pathways**: CRP is part of the body's acute-phase response to inflammation. Its levels in the blood increase rapidly in response to inflammatory cytokines, such as interleukin-6 (IL-6). This makes CRP an integral component in pathways related to the immune system's response to infection, injury, or chronic inflammatory diseases.\n", + "2. **Role in Pathways**:\n", + " - CRP plays a part in the systemic response to inflammation, often used clinically as an indicator for inflammatory conditions such as infections and autoimmune diseases. In the context described, CRP levels are used to monitor and model the effect of treatments targeting components of the IL-6 signaling pathway, especially in diseases like Crohn's disease.\n", "\n", - "- **Interactions with Other Molecules**: CRP interacts with the complement system components, particularly C1q, to initiate the complement cascade, a series of reactions that help eliminate pathogens. It also interacts with receptors on the surfaces of immune cells, such as Fcγ receptors, facilitating opsonization and phagocytosis. The document mentions interactions with IL-6 and its receptor IL-6Rα, as CRP production is highly influenced by IL-6 signaling.\n", + "3. **Interactions with Other Molecules**:\n", + " - CRP interacts with various components of the immune system. It can bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system, promoting phagocytosis by macrophages, which is a crucial aspect of its role in inflammation.\n", + " - In the context of the presented data, CRP levels are modulated through pathways involving IL-6 and its receptor (IL-6Rα), showcasing its interconnected role in immune signaling pathways.\n", "\n", - "- **Importance in Biological Systems**: In the context of the model described, CRP is used as a biomarker to assess inflammation levels in patients, particularly those with conditions such as Crohn's disease. The model measures CRP levels to validate its predictions regarding drug effects on inflammatory pathways, highlighting its utility in monitoring disease activity and treatment efficacy.\n", + "4. **Importance in the Biological System Being Modeled**:\n", + " - Within the model described, CRP serves as a key biomarker for the effectiveness of treatment strategies targeting IL-6 signaling. The modulation of CRP levels indicates the level of inflammation and the success of therapeutic interventions aimed at reducing inflammation by inhibiting IL-6 activity.\n", + " - The document suggests the use of CRP levels to validate and predict the outcomes of therapeutic interventions, underlining its importance as a measurable outcome in clinical and modeling studies.\n", "\n", - "Overall, CRP is a crucial component in biological models focused on inflammatory diseases due to its rapid and measurable response to changes in underlying inflammation.\n", + "Overall, CRP acts as an essential biomarker and participant in inflammatory pathways, and its levels are indicative of the inflammatory state and the impact of medical treatments in the studied model.\n", "\n", "================================================================================\n", "5. sR (ID: mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc)\n", "================================================================================\n", - "Based on the provided context, the species named 'sR' (ID: mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc) is likely related to the IL-6 signaling pathway. However, specific details about 'sR' are not provided directly in the context. Given that 'sR' is mentioned alongside IL-6, sIL-6R, and sgp130, it could be inferred that 'sR' is a component or modifier in the interleukin-6 (IL-6) signaling pathway.\n", - "\n", - "### Inferred Background Information\n", + "Based on the provided context, there is limited direct information regarding the species 'sR' with ID mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc. However, we can infer some details based on the context of similar biological components mentioned.\n", "\n", - "**Biological Function**:\n", - "- It is probable that 'sR' is related to IL-6 signaling, potentially as a soluble receptor or co-receptor. Soluble receptors often exist as naturally occurring antagonists or helpers of cytokine signaling, modulating the pathway's activity.\n", + "1. **Biological Function**: The context does not specify a unique biological function for 'sR'. However, it mentions interactions involving IL-6 and sIL-6R, suggesting that 'sR' might be associated with receptor or signaling functions in the IL-6 pathway. sIL-6R usually stands for soluble IL-6 receptor, which is involved in extending the effects of the IL-6 cytokine beyond cells that have membrane-bound receptors.\n", "\n", - "**Role in Pathways**:\n", - "- 'sR' might be involved in modulating the availability or activity of IL-6, similar to how sgp130 and sIL-6R work. sIL-6R is known to allow cells that do not possess membrane-bound IL-6R to respond to IL-6 through a process known as trans-signaling.\n", + "2. **Role in Pathways**: Similar to sIL-6R and other molecules like sgp130, 'sR' might play a role in the modulation of signaling pathways. IL-6 signaling pathways involve activation and modulation through receptors, influencing gene transcription and protein production. It's plausible that 'sR' participates in similar pathways, potentially affecting signal transduction and biological responses.\n", "\n", - "**Interactions with Other Molecules**:\n", - "- It may interact with IL-6 or IL-6 receptor complexes. This interaction is crucial in the modulation of the pathway, likely affecting the downstream signaling events such as the activation of STAT3 (Signal Transducer and Activator of Transcription 3).\n", + "3. **Interactions with Other Molecules**: Although not directly mentioned, 'sR' perhaps interacts with other components in the IL-6 signaling cascade such as IL-6, its receptors (like IL-6R), and possibly soluble receptors like sgp130. Intermediates such as Jak and STAT3 are common in such pathways, and 'sR' might influence or be influenced by these interactions.\n", "\n", - "**Importance in the Biological System**:\n", - "- Given its potential role in cytokine signaling, 'sR' would be important in regulating inflammatory responses, immune system signaling, and possibly in the pathophysiology of diseases where IL-6 is a key player, such as autoimmune diseases.\n", + "4. **Importance in the Biological System**: The significance of 'sR' is not explicitly described, but it could be an important regulator within the system. Given the extensive discussion on IL-6 and its modulation by soluble receptors and sgp130, 'sR' might contribute to these dynamics, affecting cellular responses to IL-6 signaling and influencing conditions like inflammatory responses or chronic disease states.\n", "\n", - "### Contextual Consideration\n", - "- The provided context includes a discussion on sensitivity analysis and the role of sgp130 with IL-6, which highlights the intricate balance within the cytokine signaling pathways. Though 'sR' is not explicitly expanded upon, understanding the dynamics of similar molecules like sIL-6R and sgp130 offers insights into its potential biological significance.\n", - " \n", - "This inferred information aligns with typical roles of soluble cytokine receptors in biological systems. However, the exact nature and function of 'sR' would require further specific details or experimental data.\n", + "In summary, while not directly detailed, 'sR' may operate similarly to other receptors or molecules in the IL-6 signaling context, playing a part in modulation, interaction, and systemic effects within biological pathways.\n", "\n", "================================================================================\n", "6. sR_IL6 (ID: mw03db56ac_8dc6_4931_ae82_fef706d2ee3d)\n", "================================================================================\n", - "The species labeled 'sR_IL6' in the context provided appears to refer to a soluble receptor for interleukin-6 (IL-6), often denoted as sIL-6R. Soluble IL-6 receptors play a crucial role in IL-6 trans-signaling pathways, which differ from classical signaling by involving the soluble receptor form (sIL-6R) rather than the membrane-bound IL-6 receptor (IL-6R).\n", + "The species \"sR_IL6,\" identified by the ID mw03db56ac_8dc6_4931_ae82_fef706d2ee3d, is likely related to the soluble interleukin-6 receptor (sIL-6R) based on the context provided. Here is an interpretation and breakdown of its role and function:\n", "\n", - "### Biological Function:\n", - "- **Soluble IL-6 Receptor (sIL-6R):** Its primary function is to bind to the cytokine IL-6, forming a complex that can activate cells that do not have membrane-bound IL-6 receptors. This process is known as \"trans-signaling\" and allows for a wider range of cells to respond to IL-6, expanding its biological effects.\n", + "1. **Biological Function**: \n", + " - sR_IL6 is likely analogous to sIL-6R, which functions as a part of the IL-6 signaling pathway. The soluble receptor binds to interleukin-6 (IL-6), facilitating its interaction with gp130, an essential component for signal transduction.\n", "\n", - "### Role in Pathways:\n", - "- **Trans-signaling Pathway:** In trans-signaling, the IL-6/sIL-6R complex associates with the membrane protein gp130, facilitating intracellular signaling cascades such as the JAK/STAT pathway. This activation leads to gene transcription and biological responses in target cells.\n", - "- **Classical Signaling Pathway:** sIL-6R is involved in sequestering IL-6 in the presence of the regulatory protein sgp130, modulating the signaling capacity by preventing excessive inflammatory signaling.\n", + "2. **Role in Pathways**:\n", + " - IL-6 can signal through classical and trans-signaling pathways. In the classical pathway, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), while in the trans-signaling pathway, the soluble receptor (sIL-6R) binds IL-6, allowing the complex to interact with gp130 on cells that do not express IL-6R. This interaction is crucial for activating downstream signaling pathways, such as the JAK/STAT pathway, specifically promoting STAT3 phosphorylation (pSTAT3), which can lead to gene transcription including the acute phase protein C-reactive protein (CRP).\n", "\n", - "### Interactions with Other Molecules:\n", - "- **IL-6:** The soluble receptor interacts with IL-6 to initiate trans-signaling.\n", - "- **gp130:** Binds the IL-6/sIL-6R complex, essential for downstream signal transduction.\n", - "- **sgp130:** Acts as a natural inhibitor by sequestering IL-6/sIL-6R complexes, dampening potential overactivation of IL-6 signaling.\n", + "3. **Interactions with Other Molecules**:\n", + " - sR_IL6 (sIL-6R) interacts directly with IL-6 to form the IL-6/sIL-6R complex. This complex can be sequestered by the soluble gp130 (sgp130), inhibiting the signaling and potentially modulating the intensity or range of the IL-6 mediated response.\n", "\n", - "### Importance in the Biological System:\n", - "In the context of Crohn's disease and immune regulation, the IL-6/sIL-6R complex plays a critical role. Modulating this pathway can influence disease progression and therapeutic outcomes. Targeting the IL-6/sIL-6R complex could offer promising treatments by adjusting the immune response and inflammation characteristic of the condition.\n", + "4. **Importance in the Biological System**:\n", + " - The IL-6/sIL-6R complex plays a role in immune regulation, as indicated by its involvement in models studying conditions like Crohn’s disease. It has significance in how inflammation is managed within the body, especially in the context of inflammatory diseases.\n", + " - The model indicates the regulation of sR_IL6 levels may impact therapeutic strategies, with alterations in dosages of anti-IL-6 antibodies showing variable efficacy.\n", "\n", - "The context suggests that sIL-6R could be involved in a model for chronic inflammatory conditions, highlighting its significance in promoting or inhibiting inflammation through different signaling pathways. By understanding its interactions and functions, potential strategies can be developed for therapeutic interventions, such as using antibodies to modify its activity.\n", + "Overall, the sR_IL6 is a critical component in mediating IL-6 trans-signaling, thus having a significant impact on immune regulation and potential therapeutic strategies for inflammatory diseases.\n", "\n", "================================================================================\n", "7. Ab (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded)\n", "================================================================================\n", - "Based on the provided documents, there isn't direct and specific information regarding the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded) in the given context. However, based on general knowledge and context clues, 'Ab' likely refers to an antibody, given the reference to serum Ab concentrations and interaction with IL-6 and sIL-6Rα complexes.\n", + "Based on the provided context from the documents, the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded, located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e) is likely referring to an antibody, given the context in which it's mentioned, particularly in relation to drug doses and targeting of specific molecular complexes.\n", + "\n", + "Here are the inferred details about 'Ab' based on the context:\n", "\n", - "1. **Biological Function**: Antibodies (Ab) are proteins produced by the immune system that recognize and bind to specific antigens, such as pathogens (viruses, bacteria) or other target molecules. Their primary function is to neutralize these antigens and facilitate their destruction by other immune cells.\n", + "- **Biological Function**: The antibody ('Ab') likely functions in binding to specific target molecules, probably related to the immune system or inflammation pathways, as inferred from the association with IL-6/sIL-6Rα complexes—the interleukin-6 receptor alpha complex.\n", "\n", - "2. **Role in Pathways**: In the context provided, 'Ab' is involved in targeting the IL-6 and IL-6Rα pathways. This is indicative of its role in modulating inflammatory responses, likely through the inhibition of the IL-6 signaling pathway.\n", + "- **Role in Pathways**: 'Ab' seems to play a role in modulating pathways related to inflammatory responses, especially through interactions with the IL-6 signaling pathway. It appears to be part of a therapeutic strategy, potentially targeting cytokines such as IL-6 and its soluble receptor complex to regulate inflammation, as noted by the mention of CRP suppression (C-reactive protein—a marker for inflammation).\n", "\n", - "3. **Interactions with Other Molecules**: The document mentions the anti-IL-6 Ab dose response and its effects on serum CRP suppression. The interaction specifically involves the binding of the antibody to IL-6 and the IL-6/sIL-6Rα complex, which suggests its use in blocking or reducing the inflammatory signaling mediated by these molecules.\n", + "- **Interactions with Other Molecules**: The context suggests a role in interacting with IL-6 and sIL-6Rα complexes. The antibody serves as a limiting factor in neutralizing or modulating these complexes within the biological system, influencing serum biomarker levels like CRP.\n", "\n", - "4. **Importance in the Biological System**: The blocking or modulation of IL-6 signaling by antibodies plays a significant role in managing inflammatory diseases. The context implies that targeting IL-6 and its receptor complexes can be part of a therapeutic strategy for conditions characterized by excessive inflammation, such as inflammatory bowel diseases.\n", + "- **Importance in the Biological System Being Modeled**: 'Ab' is significant in the modeled system as a therapeutic agent, potentially used in treating inflammatory conditions by targeting cytokine pathways. By affecting IL-6-related pathways, it appears to reduce inflammatory responses, as evidenced by experiments and modeling of serum CRP suppression following treatments.\n", "\n", - "Given these points, 'Ab' in this context seems to be associated with therapeutic antibodies used to manage inflammation by interfering with specific cytokine pathways, particularly involving IL-6. This type of intervention is crucial in diseases where cytokine signaling contributes to the pathology.\n", + "Though specific details about 'Ab' are not explicitly provided in the excerpts, it can be inferred that 'Ab' is a therapeutic antibody with a function in targeting pro-inflammatory cytokine pathways within the given biological context, aiming to control or reduce inflammatory processes.\n", "\n", "================================================================================\n", "8. Ab_sR (ID: mw1da111f2_a036_4392_8512_015005bdcbb7)\n", "================================================================================\n", - "The specific species 'Ab_sR' (ID: mw1da111f2_a036_4392_8512_015005bdcbb7) located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e does not seem to be explicitly mentioned in the provided context. However, based on the context and general knowledge, we can infer some relevant background information about similar biological components that usually appear in such contexts. \n", + "Based on the provided context, specific information about the species \"Ab_sR\" (ID: mw1da111f2_a036_4392_8512_015005bdcbb7, located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e) is not directly mentioned. However, we can infer its potential role and importance in the biological system being modeled by examining the surrounding biological components and pathways mentioned in the context.\n", "\n", - "The context mentions components such as sIL-6R, IL-6, and their interactions, which are indicative of a role in inflammatory response pathways. sIL-6R is a soluble form of the IL-6 receptor, and it typically participates in what's known as IL-6 trans-signaling. In this process, instead of the membrane-bound receptor, IL-6 binds to sIL-6R to form a complex that can interact with the gp130 protein, initiating signaling cascades even in cells that do not express the full receptor. This mechanism is important in regulating immune responses, inflammation, and possibly chronic inflammatory diseases by influencing the production of acute-phase proteins like C-reactive protein (CRP).\n", + "### Inferred Background Information about Ab_sR\n", "\n", - "Given this understanding, 'Ab_sR' could potentially refer to an antibody or an interaction factor related to the soluble receptor pathways, possibly playing a regulatory or inhibitory role in these pathways through binding interactions. Its importance might then be deduced from its capability to modulate these signaling pathways, with potential therapeutic implications for diseases driven by excessive IL-6 signaling.\n", + "1. **Biological Function:**\n", + " - The context suggests a focus on interleukin-6 (IL-6) and its receptor interactions, particularly involving the soluble IL-6 receptor (sIL-6R) and its complexes. Given the naming convention \"Ab_sR,\" it is reasonable to infer that Ab_sR could represent an antibody (Ab) specific to a soluble receptor (sR), likely related to the IL-6 signaling pathway.\n", + "\n", + "2. **Role in Pathways:**\n", + " - The IL-6 signaling pathway involves several key interactions, including the formation of complexes with sIL-6R, which are critical for signal transduction. Ab_sR might participate in modulating or inhibiting this pathway, possibly by binding to the sIL-6R or other pathway components, potentially altering the pathway's output like the downstream effects on C-reactive protein (CRP) production.\n", "\n", - "If Ab_sR is an antibody, it could play a role similar to antibodies against IL-6 or IL-6Rα, aiming to disrupt or modify these signaling pathways, potentially reducing inflammatory responses as a therapeutic strategy. Such antibodies are being explored in contexts of autoimmune diseases, cancers, and inflammatory disorders. \n", + "3. **Interactions with Other Molecules:**\n", + " - Within the pathway context, Ab_sR may interact with IL-6, sIL-6R, and possibly other related components like the glycoprotein (gp130), which are crucial for IL-6 signal transduction. Its role might be to bind these molecules to modulate their activity or bioavailability in the system, akin to the action of therapeutic antibodies that target cytokine receptors.\n", + "\n", + "4. **Importance in the Biological System:**\n", + " - Ab_sR could be significant for fine-tuning the inflammatory response mediated by IL-6 signaling. By regulating or inhibiting the function of the IL-6/sIL-6R pathway, Ab_sR might contribute to controlling inflammation and related processes in tissues such as the liver and gastrointestinal tract. This modulation could be especially important in conditions where IL-6 plays a pivotal role, such as in autoimmune diseases or chronic inflammatory states.\n", "\n", - "Note: This inference is made based on the context provided and common biological functions of related components. Further specific information would be required for more accurate detailing of Ab_sR's role.\n", + "Overall, while direct information on Ab_sR is not available, the context allows us to hypothesize its role as a regulatory or inhibitory agent within the IL-6 signaling pathway, potentially serving as a therapeutic molecule targeting inflammation-related pathways.\n", "\n", "================================================================================\n", "9. Ab_sR_IL6 (ID: mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac)\n", "================================================================================\n", - "The context provided does not directly specify information about a species named 'Ab_sR_IL6'. However, based on general knowledge and the context given, we can make some inferences and provide related information:\n", + "Based on the context provided, there is no specific mention of the species 'Ab_sR_IL6' by name. However, the context revolves around interactions involving IL-6, its receptor sIL-6Rα, and antibodies targeting these molecules. We can infer certain characteristics and roles this species might fulfill based on the general knowledge of similar biological components and the information presented:\n", "\n", - "1. **Biological Function**: Given the naming convention used ('Ab_sR_IL6'), it is likely that this refers to an antibody (Ab) targeting a soluble receptor (sR) for interleukin-6 (IL-6), possibly inhibiting its action. IL-6 is a cytokine involved in inflammatory and immune responses.\n", + "1. **Biological Function**: Proteins associated with the suffix 'Ab' usually refer to antibodies. Given the context, 'Ab_sR_IL6' likely functions as an antibody targeting the IL-6 receptor, specifically the soluble form sIL-6Rα. Antibodies like these are typically designed to bind to their target receptor, potentially blocking its interaction with its ligand (IL-6) or other molecules, resulting in modulation of a biological pathway.\n", "\n", - "2. **Role in Pathways**: IL-6 typically signals through its receptor complex, including IL-6R and gp130, to activate downstream signaling pathways like JAK/STAT, leading to the activation of transcription factors such as STAT3. This cascade leads to the expression of various genes involved in inflammation and immune regulation.\n", + "2. **Role in Pathways**: In the immune regulation context, this antibody likely plays a role in modulating IL-6-mediated signaling pathways. The data discusses targeting the IL-6/sIL-6Rα complex to modulate responses in the immune system, particularly in inflammatory conditions like Crohn’s Disease and rheumatoid arthritis. By interfering with this pathway, the antibody likely serves to suppress the pro-inflammatory effects mediated by IL-6.\n", "\n", - "3. **Interactions with Other Molecules**: Based on the context, the antibody could be interacting with the IL-6/sIL-6R complex to modulate its effects. The text describes interactions involving sIL-6R and IL-6, potentially including competition or inhibition by antibodies that alter the signaling outcomes and inflammatory responses.\n", + "3. **Interactions with Other Molecules**: The document specifically talks about the interaction of antibodies with sIL-6Rα and IL-6, suggesting that 'Ab_sR_IL6' could interact with these components. The interaction with sIL-6Rα likely prevents the receptor from associating with IL-6 or gp130 (another crucial signaling component). This interference can result in reduced signaling through the JAK-STAT pathway, which is implicated in inflammation and autoimmune disease processes.\n", "\n", - "4. **Importance in the Biological System Being Modeled**: In the context of the model described, inhibiting the IL-6/sIL-6R interaction is a focus, likely due to its role in conditions like Crohn's Disease or rheumatoid arthritis. Modifying this pathway's activity through an antibody such as 'Ab_sR_IL6' might be of therapeutic significance, potentially helping to suppress excessive inflammatory responses, as suggested by the interest in CRP (C-reactive protein) suppression and dose-response relationships.\n", + "4. **Importance in the Biological System**: The importance of such an antibody in the model is likely related to its ability to control inflammatory processes. By targeting sIL-6Rα, it could help reduce the production of inflammatory mediators like C-reactive protein (CRP) and other gene products important in the inflammatory response. In the context of diseases like Crohn’s Disease, the use of such an antibody could be significant for reducing symptoms and controlling disease progression.\n", "\n", - "In summary, 'Ab_sR_IL6' is likely conceptualized as an antibody targeting the soluble IL-6 receptor to interfere with IL-6 mediated signaling pathways, which are pivotal in certain inflammatory diseases. While specific details are not provided in the context, this inference aligns with common therapeutic strategies involving cytokine signaling modulation.\n", + "Given these points, 'Ab_sR_IL6' likely represents a therapeutic antibody targeted towards IL-6 signaling components, playing a crucial role in modulating immune responses in inflammatory diseases.\n", "\n", "================================================================================\n", "10. CRP Suppression (%) (ID: CRP_Suppression___)\n", "================================================================================\n", - "Based on the context provided, \"CRP Suppression (%)\" refers to the measurement of the reduction in serum C-reactive protein (CRP) levels. CRP is a biological marker of inflammation, and its levels can be indicative of inflammatory responses in the body. Understanding the suppression of CRP levels has the following implications:\n", + "CRP Suppression (%) refers to the extent to which the levels of C-reactive protein (CRP) in the serum are reduced from baseline levels. CRP is a biomarker typically used to assess inflammation and is often elevated in response to inflammatory conditions such as infections, chronic diseases, or autoimmune disorders.\n", "\n", - "1. **Biological Function**: CRP is an acute phase protein, produced by the liver in response to inflammation. It plays a role in the body's immune response, indicating tissue damage or inflammation.\n", + "### Biological Function:\n", + "- **C-reactive protein (CRP):** CRP is a protein produced by the liver in response to inflammation. It is part of the body's immune response and acts as an opsonin, marking pathogens for destruction by immune cells.\n", "\n", - "2. **Role in Pathways**: CRP is involved in the inflammatory pathway. Suppressing CRP levels typically suggests an underlying modulation of the inflammatory response, often facilitated through interventions like antibodies targeting specific inflammatory cytokines or receptors, such as IL-6 or IL-6Rα in this context.\n", + "### Role in Pathways:\n", + "- **Inflammatory Pathways:** The suppression of CRP levels is a marker of reduced inflammation. In the context of treatments targeting cytokines like interleukin-6 (IL-6), the decrease in CRP is an indicator of the efficacy of such anti-inflammatory treatments.\n", "\n", - "3. **Interactions with Other Molecules**: The context implies interactions with Interleukin-6 (IL-6) and its receptor (IL-6Rα). Treatments with anti–IL-6 or anti–IL-6Rα antibodies reduce CRP levels, thereby modulating inflammation, as indicated by the provided data on drug dose and CRP suppression.\n", + "### Molecular Interactions:\n", + "- **Interaction with Interleukin-6 (IL-6):** IL-6 is a cytokine that stimulates CRP production. Anti-IL-6 or anti-IL-6 receptor therapies aim to reduce CRP levels by blocking the action of IL-6, thereby diminishing its signal for CRP synthesis.\n", "\n", - "4. **Importance in the Biological System**: Suppression of serum CRP is an important indicator of the efficacy of drugs, like anti-IL-6 or anti-IL-6Rα antibodies, in reducing inflammatory responses. This makes CRP suppression a critical measure for evaluating the outcome of therapeutic interventions aimed at inflammatory diseases.\n", + "### Importance in the Biological System Being Modeled:\n", + "- **Treatment Efficacy Marker:** CRP Suppression (%) is used as a biomarker to evaluate the effectiveness of treatments, such as anti-IL-6 antibodies or anti-IL-6R antibodies, in reducing inflammation. The suppression percentage directly correlates with the reduction in inflammatory activity within the body.\n", + "- **Dose-response Analysis:** The relationship between drug dosage and CRP Suppression (%) is crucial for determining optimal dosing regimens. Increased CRP suppression with higher doses of anti-inflammatory drugs typically indicates greater efficacy, though it may plateau or saturate at certain dose levels.\n", "\n", - "While the context does not directly describe CRP Suppression (%) as a biological species, it is a measure of the effectiveness of treatments targeting inflammatory pathways. Interactions that lead to its suppression are essential for understanding therapeutic impacts on inflammation-related conditions.\n", + "In summary, CRP Suppression (%) serves as a critical indicator for assessing the impact of therapeutic strategies aimed at managing inflammatory responses by targeting specific immune signaling pathways in the body.\n", "\n", "================================================================================\n", "11. CRP (% of baseline) (ID: CRP____of_baseline)\n", "================================================================================\n", - "The term \"CRP (% of baseline)\" is referring to C-reactive protein (CRP) levels measured as a percentage of a baseline value. In the context provided, it appears to be a metric used in the modeling and analysis of clinical trial data related to anti–IL-6Rα antibody treatments, specifically tocilizumab, which is an anti-inflammatory medication. Here's a summary based on the context and general knowledge about CRP:\n", + "Based on the context provided and general knowledge about C-reactive protein (CRP), I can summarize the following background information:\n", "\n", - "1. **Biological Function:**\n", - " - CRP is a protein produced by the liver in response to inflammation. It is part of the acute phase response to inflammation and is a biomarker commonly used to assess inflammation and tissue injury.\n", + "1. **Biological Function**:\n", + " - CRP, or C-reactive protein, is a substance produced by the liver in response to inflammation. It is a member of the class of acute-phase proteins, which increase in concentration in response to inflammation. CRP is commonly measured in clinical settings as a marker of inflammation.\n", "\n", - "2. **Role in Pathways:**\n", - " - CRP is a key player in the acute inflammatory response and is involved in pathways that react to injury, infection, and inflammation. It interacts with the immune system to facilitate the clearance of necrotic and apoptotic cells and bacteria.\n", + "2. **Role in Pathways**:\n", + " - CRP is part of the body's immune response and plays a role in recognizing pathogens and damaged cells, thereby promoting their clearance through interaction with the complement system and other immune pathways. The context involving IL-6 and anti–IL-6Rα antibody treatment suggests an interest in inflammatory pathways where CRP is a downstream marker of cytokine (like IL-6) activity.\n", "\n", - "3. **Interactions with Other Molecules:**\n", - " - CRP levels are influenced by the presence of pro-inflammatory cytokines, particularly interleukin-6 (IL-6). This context highlights the interaction between CRP levels and anti–IL-6Rα antibodies, which inhibit IL-6 signaling and therefore can suppress CRP production as part of their therapeutic action.\n", + "3. **Interactions with Other Molecules**:\n", + " - CRP interacts with phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) to activate the complement system. It is known that CRP levels are regulated by cytokines, particularly interleukin-6 (IL-6), which is relevant in the context of anti-IL-6 therapy described in the document.\n", "\n", - "4. **Importance in the Biological System Being Modeled:**\n", - " - In the given context, CRP (% of baseline) serves as an important biomarker for evaluating the efficacy of tocilizumab treatment in suppressing inflammation. The model uses CRP levels to compare and validate simulation results against clinical trial data, indicating its critical role in assessing treatment impacts.\n", + "4. **Importance in the Biological System Being Modeled**:\n", + " - The suppression and modulation of serum CRP levels are used as a measure to validate models simulating the effects of anti-IL-6Rα antibody therapy (such as with tocilizumab) in clinical settings. In this context, CRP (% of baseline) acts as a biomarker to assess the efficacy of treatment options targeting inflammatory pathways and the IL-6 signaling axis. It indicates the level of inflammation within patients undergoing such treatments.\n", "\n", - "No specific unique details beyond this general framework are detailed in the context, but from a systems biology perspective, CRP measurement is significant for understanding inflammatory processes and the body's response to therapeutic interventions.\n", + "The reference to CRP (% of baseline) reflects normalized data used to compare changes in serum CRP levels over time, particularly in response to medical interventions, such as administration of anti-inflammatory drugs. This emphasizes its utility as a reliable marker for evaluating treatment responses in clinical trials and models related to inflammatory diseases.\n", "\n", "================================================================================\n", "12. gp130 (ID: mw80848184_e2dd_47ce_86d7_7a21479342bd)\n", "================================================================================\n", - "The species named 'gp130' refers to a protein that plays a significant role in the signaling pathway involving interleukin-6 (IL-6) and its receptor. \n", + "Based on the provided context, the biological species named 'gp130' appears to be a critical component in the interleukin-6 (IL-6) signaling pathway. Here's a summary of its role and importance:\n", "\n", "### Biological Function:\n", - "- **gp130 is a Signal Transducer**: It is primarily a signal-transducing component of the IL-6 receptor complex. It does not bind IL-6 by itself but acts as a signal transducer when associated with IL-6 and IL-6 receptor (IL-6R).\n", + "- **Gp130** serves as a signal-transducing coreceptor in the IL-6 signaling pathway.\n", + "- It acts as part of a complex with the IL-6 receptor (IL-6R) and is involved in mediating the downstream effects of IL-6.\n", "\n", "### Role in Pathways:\n", - "- **Interaction with IL-6/IL-6R**: gp130 is crucial in the formation of the signaling complex with IL-6 and its soluble receptor sIL-6R. This complex is central to IL-6 signaling pathways.\n", - "- **Inhibition of IL-6 Trans-Signaling**: A fusion protein known as sgp130Fc, which combines the extracellular portion of gp130 with an Fc region, has been shown to inhibit IL-6 trans-signaling, demonstrating gp130’s role in regulatory mechanisms.\n", + "- **IL-6 Signaling**: Gp130 is a key component in the assembly of the IL-6/IL-6R/gp130 complex. This is crucial for the signaling cascade that drives various inflammatory and immune responses.\n", + "- **Inhibition of IL-6 Trans-Signaling**: The soluble form of gp130 (sgp130) can inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing its interaction with membrane-bound gp130 and subsequent signaling.\n", "\n", "### Interactions with Other Molecules:\n", - "- **Complex Formation**: It forms a complex with IL-6 and IL-6R, contributing to signal transduction.\n", - "- **Natural Inhibitor**: Soluble gp130 (sgp130) serves as a natural inhibitor of the IL-6/sIL-6R signaling pathway, preventing excessive signal transduction.\n", + "- **IL-6 and IL-6R**: Gp130 interacts with IL-6 bound to its receptor IL-6R, forming a complex necessary for initiating signal transduction.\n", + "- **Soluble IL-6 Receptor (sIL-6R)**: It is noted that sgp130 is a natural inhibitor of the soluble IL-6 receptor, indicating a regulatory role in modulating the availability and activity of IL-6.\n", "\n", "### Importance in the Biological System:\n", - "- **Regulatory Role**: The high baseline level of soluble gp130 (sgp130) in the system acts as a buffering agent against changes in the levels of IL-6/sIL-6R complex, highlighting its regulatory importance.\n", - "- **Therapeutic Potential**: Therapeutic approaches using sgp130 to target IL-6 signaling pathways, such as in the treatment of Crohn’s disease, underscore its clinical significance.\n", - " \n", - "Given these roles, gp130 is a critical component in the IL-6 signaling pathway and has potential therapeutic implications due to its regulatory capacities in controlling inflammatory responses.\n", + "- Gp130 is vital for the modulation of immune responses and inflammation through its role in IL-6 signaling.\n", + "- **Therapeutic Potential**: Its soluble form, sgp130, has been studied for therapeutic applications, including its potential use in diseases characterized by excessive IL-6 signaling, such as Crohn's disease. The context mentions simulations of sgp130Fc (a fusion protein of sgp130 with the Fc region of an antibody) for therapeutic dosing.\n", + "- **Baseline Levels**: The high baseline levels of sgp130 compared to IL-6 indicate its prominent regulatory role in the signaling environment.\n", + "\n", + "In summary, gp130 is a crucial component of the IL-6 signaling pathway with significant implications in inflammation and immune modulation. Its interactions and regulatory capabilities make it a target for therapeutic intervention, especially in inflammatory diseases.\n", "\n", "================================================================================\n", "13. R_IL6_gp130 (ID: mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a)\n", "================================================================================\n", - "The species named 'R_IL6_gp130', based on its naming and the context provided, likely refers to a complex or interaction involving the cytokine interleukin-6 (IL-6) and the signal transducer glycoprotein 130 (gp130). While the specific document does not provide detailed information about R_IL6_gp130, general knowledge about the IL-6/gp130 interaction helps us understand its potential biological significance.\n", + "Based on the context and general knowledge about similar biological components, the species 'R_IL6_gp130' likely refers to a complex involving interleukin-6 (IL-6), its receptor (IL-6R), and the signaling component gp130. Here's a summary of what is generally known about the components involved:\n", "\n", - "### Biological Function:\n", - "- **IL-6:** It is a cytokine involved in the regulation of immune responses, inflammation, and hematopoiesis. It plays a crucial role in acute phase responses and is produced at sites of inflammation.\n", - "- **gp130:** It serves as a signal transducer in the cytokine receptor complex, particularly for the IL-6 family of cytokines. It is involved in several cellular processes, including cell growth and differentiation.\n", + "1. **Biological Function:**\n", + " - Interleukin-6 (IL-6) is a cytokine involved in immune responses, inflammation, and hematopoiesis. It mediates its effects through the IL-6 receptor (IL-6R) and the signal transducer gp130.\n", + " - gp130 is a transmembrane protein that, upon IL-6 binding to IL-6R, forms a complex through which signal transduction occurs, initiating intracellular signaling cascades primarily involving the JAK-STAT pathway.\n", "\n", - "### Role in Pathways:\n", - "- The IL-6/gp130 interaction is central to both classical and trans-signaling pathways. In classical signaling, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), which then associates with gp130 to initiate downstream signaling.\n", - "- In trans-signaling, IL-6 binds to a soluble form of the IL-6 receptor (sIL-6R), and this complex can then associate with gp130 on the target cell surface, allowing cells that do not express membrane-bound IL-6R to respond to IL-6.\n", + "2. **Role in Pathways:**\n", + " - The IL-6/IL-6R/gp130 signaling complex plays a crucial role in the JAK-STAT signaling pathway. This pathway is pivotal in promoting gene expression associated with inflammatory responses.\n", + " - The pathway can occur through classical signaling, where IL-6 binds to its membrane-bound receptor IL-6R, or through trans-signaling, where IL-6 binds to a soluble form of IL-6R (sIL-6R), interacting with membrane-bound gp130 in cells that do not express IL-6R.\n", "\n", - "### Interactions with Other Molecules:\n", - "- gp130 is a common subunit shared by several cytokine receptors in the IL-6 family, meaning it participates in a variety of signaling complexes.\n", - "- The soluble form of gp130 (sgp130) can act as a natural inhibitor by binding to IL-6/sIL-6R complexes and preventing them from interacting with membrane-bound gp130.\n", + "3. **Interactions with Other Molecules:**\n", + " - IL-6 binding to IL-6R and subsequent interaction with gp130 triggers gp130 dimerization and activation of associated JAK kinases, leading to phosphorylation and activation of STAT3, a transcription factor.\n", + " - Soluble gp130 (sgp130) can inhibit IL-6-mediated trans-signaling by binding to the IL-6/sIL-6R complex, preventing it from interacting with membrane-bound gp130. This natural inhibitor is significant as it selectively inhibits the trans-signaling pathway.\n", "\n", - "### Importance in the Biological System Being Modeled:\n", - "- Given the context of inflammatory diseases such as Crohn’s disease, the IL-6/gp130 axis is likely a critical component in the inflammatory response modulation.\n", - "- The application of sgp130, or its fusion forms like sgp130Fc, demonstrates the pathway's therapeutic significance as a target for damping excessive IL-6-mediated signaling in inflammatory diseases.\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - The IL-6/gp130 signaling axis is critical in inflammatory diseases, including Crohn's disease and other autoimmune conditions. The document highlights the therapeutic potential of modulating this pathway, particularly using sgp130Fc (a fusion protein analog of gp130) to inhibit IL-6 trans-signaling.\n", + " - Pharmacokinetic (PK) studies and simulations of sgp130Fc are mentioned, indicating its evaluation as a therapeutic intervention targeting this pathway, aiming to reduce inflammation markers like CRP (C-reactive protein) and pSTAT3 in the gut.\n", "\n", - "In summary, R_IL6_gp130 refers to a key interaction in the IL-6 signaling pathway, emphasizing its role in inflammatory responses and its potential as a therapeutic target in autoimmune diseases like Crohn's.\n", + "In summary, 'R_IL6_gp130' likely represents a signaling complex crucial for mediating inflammatory responses in various biological settings, making it a significant therapeutic target, especially in inflammatory and autoimmune diseases.\n", "\n", "================================================================================\n", "14. sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw4638f126_8cb8_4021_ab41_6ae195743ba0)\n", "================================================================================\n", - "Based on the provided context and general knowledge, here is the background information on the species 'sR_IL6' with the identifier 'mw4638f126_8cb8_4021_ab41_6ae195743ba0', situated within 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e':\n", + "The molecule in question, sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2), can be inferred to relate closely to soluble IL-6 receptor components based on its name and ID positioning within a model of IL-6 signaling. Although there is no explicit information about this exact species in the provided context, some relevant points about similar molecules can be derived.\n", "\n", - "1. **Biological Function**: 'sR_IL6' likely refers to the soluble receptor for Interleukin-6 (sIL-6R). Soluble receptors such as sIL-6R can bind to the cytokine IL-6, acting as a co-receptor that allows IL-6 to engage in signaling pathways even in cells that do not express the membrane-bound IL-6 receptor.\n", + "### **Biological Function:**\n", + "- **sIL-6R (soluble IL-6 receptor)**: Typically, sIL-6R refers to a soluble form of the IL-6 receptor, which allows IL-6 to transduce signals through cells that do not express the membrane-bound IL-6 receptor. This process is part of what is known as IL-6 trans-signaling. In the context of the model being described, sR_IL6 may play a similar role.\n", "\n", - "2. **Role in Pathways**: In the immune system, IL-6 can signal through two main pathways:\n", - " - **Classical signaling**: IL-6 binds to membrane-bound IL-6R and recruits the gp130 protein to initiate downstream signaling.\n", - " - **Trans-signaling**: sIL-6R, in complex with IL-6, engages gp130 on cells that do not have the IL-6 receptor, thus expanding the range of cells that can respond to IL-6. This is particularly relevant in inflammatory responses and is studied in contexts such as Crohn's disease.\n", + "### **Role in Pathways:**\n", + "- **IL-6 Signaling**: It functions within the IL-6 signaling pathway, which can occur via classical signaling or trans-signaling. Classical signaling involves membrane-bound IL-6R and gp130, while trans-signaling involves sIL-6R.\n", + "- **Interaction with sgp130**: The sIL-6R/IL-6 complex can be sequestered by another molecule, sgp130, preventing further signaling.\n", "\n", - "3. **Interactions with Other Molecules**: \n", - " - sIL-6R forms a complex with IL-6 which can then bind to gp130, leading to activation of downstream signaling pathways such as the JAK/STAT pathway.\n", - " - sIL-6R can be sequestered by sgp130, a soluble form of gp130, which can regulate the availability of the IL-6/sIL-6R complex for signaling.\n", - " - C-reactive protein (CRP) is involved in the production of sIL-6R through a process known as CRP-mediated shedding.\n", + "### **Interactions with Other Molecules:**\n", + "- **IL-6/sIL-6R Complex**: It forms a complex with IL-6, which can engage with gp130 on cell membranes, activating downstream signaling cascades.\n", + "- **CRP Influence**: The production of sIL-6R is influenced by CRP (C-reactive protein), which mediates its shedding.\n", "\n", - "4. **Importance in the Biological System**: \n", - " - sIL-6R plays a crucial role in mediating IL-6 trans-signaling, particularly in contexts like chronic inflammation and autoimmune diseases such as Crohn's disease.\n", - " - The presence of sIL-6R enables IL-6 to exert its effects even in cells lacking direct IL-6 receptors, thereby widening its scope of action within the immune regulatory processes.\n", - " - Understanding the dynamics of sIL-6R in combination with IL-6 is important for therapeutic considerations, as targeting these complexes can influence pharmacological outcomes in disease states.\n", + "### **Importance in the Biological System Being Modeled:**\n", + "- **Crohn’s Disease**: The IL-6/sIL-6Rα complex plays a significant role in the context of Crohn’s disease, a chronic inflammatory condition. Therapeutic strategies targeting this complex have been simulated to evaluate their effects on disease dynamics.\n", + "- **Pharmacological Efficacy**: In therapeutic models, blocking the IL-6/sIL-6Rα complex alongside free IL-6 has been shown to improve pharmacological efficacy, implying its critical role in modulating immune responses.\n", "\n", - "Thus, sR_IL6 (inferred as sIL-6R) is integral to the IL-6 signaling pathways, facilitating broad immunological responses through its role in trans-signaling and interaction with IL-6 and other molecular regulators like sgp130.\n", + "In summary, sR_IL6 is likely involved in facilitating trans-signaling in IL-6 pathways, interacting with other components like IL-6, gp130, and CRP, with implications for inflammatory diseases such as Crohn’s disease. These inferred roles suggest its significance in the physiological and pathological contexts of IL-6 mediated immune regulation.\n", "\n", "================================================================================\n", "15. R (ID: mw10315fa3_6f13_4618_bda8_a8694bd3c374)\n", "================================================================================\n", - "Given the context provided, the information about the species named 'R' (ID: mw10315fa3_6f13_4618_bda8_a8694bd3c374) is not directly mentioned in the documents. However, we can make inferences based on the information about related molecules and pathways described in the context, particularly those involving IL-6 (interleukin-6) and its receptor.\n", - "\n", - "### Inferred Background Information about 'R':\n", + "The provided context refers to interactions and functions related to the interleukin-6 receptor (IL-6R), yet there is no explicit mention of a species or molecule specifically called 'R'. However, we can infer that 'R' might refer to the interleukin-6 receptor (IL-6R) or components associated with it based on the context of the documents provided. Here's a summary of relevant information that could be applicable to 'R', especially if it is related to IL-6R:\n", "\n", "1. **Biological Function**:\n", - " - Since the context discusses IL-6 and its receptors (sIL-6R and IL-6Rα), 'R' could potentially be related to components in the IL-6 signaling pathway. IL-6 is a cytokine involved in inflammation and immune response regulation.\n", + " - The IL-6 receptor (IL-6R) plays a critical role in the immune response. It is involved in the signaling pathway for interleukin-6 (IL-6), a cytokine that influences immune regulation, inflammation, and hematopoiesis.\n", "\n", "2. **Role in Pathways**:\n", - " - IL-6 interacts with both membrane-bound and soluble forms of its receptor (IL-6R) to initiate downstream signaling cascades, such as the JAK/STAT pathway, which leads to the activation of transcription factors like STAT3 (signal transducer and activator of transcription 3).\n", - " - The pathway is involved in the transcription of various genes, including those coding for acute-phase proteins like CRP (C-reactive protein), indicating a role in inflammatory processes and liver function.\n", - "\n", + " - IL-6R is a part of the Classical and Trans signaling pathways. In the Classical pathway, it binds IL-6, leading to dimerization with gp130 and activation of the JAK/STAT signaling cascade, particularly resulting in the phosphorylation and activation of STAT3. This pathway has significant implications for transcriptional regulation of various genes.\n", + " - The IL-6 trans-signaling involves soluble IL-6R (sIL-6R) and affects cells that do not naturally express IL-6R on their surface, further enabling broader physiological effects.\n", + " \n", "3. **Interactions with Other Molecules**:\n", - " - IL-6, in combination with its receptor, can activate a signaling complex that involves the JAK proteins and STAT3, influencing gene expression. Soluble forms of the receptor, such as sIL-6R, play a role in trans-signaling, which can modulate responses in cells that do not express the membrane-bound receptor.\n", + " - IL-6R interacts with IL-6 and gp130 in both the Classical and Trans signaling pathways.\n", + " - Antibodies targeting IL-6R, such as those mentioned in the context (e.g., anti–IL-6Rα antibodies), are used to modulate its function, particularly as therapeutic interventions to reduce inflammation or lower C-reactive protein (CRP) levels.\n", "\n", "4. **Importance in the Biological System**:\n", - " - Given that IL-6 signaling impacts acute-phase response and immune regulation, molecules within this pathway, including 'R' if it is part of this system, are crucial for modulating inflammatory responses. They may be targeted in therapeutic contexts, such as with anti–IL-6 or anti–IL-6Rα therapies, which are indicated in the documents as treatments influencing biomarkers like CRP.\n", + " - In the context of disease and therapy, IL-6R is a target for modulating inflammatory responses, as its activation leads to increased levels of acute-phase proteins such as CRP, which are markers for inflammation.\n", + " - The modulation of IL-6R, such as through the use of antibodies, is significant in clinical settings for managing conditions characterized by excessive inflammation or immune activation.\n", "\n", - "In conclusion, without specific data directly linked to 'R', it can be inferred that 'R' is potentially part of the IL-6 pathway components, involved in immune and inflammatory responses, and plays a significant role in cellular signaling and communication within this biological system.\n", + "Based on the described interactions and importance, if 'R' refers to the IL-6 receptor or a similar component, it acts as a central mediator in inflammatory pathways and is a critical target for therapeutic interventions.\n", "\n", "================================================================================\n", "16. IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1)\n", "================================================================================\n", - "Based on the context provided, the species referred to as 'IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is likely Interleukin-6 (IL-6), a cytokine involved in various biological processes. Here is a summary of relevant background information about IL-6:\n", + "Based on the context provided and general knowledge about IL-6, here is a summary of the information regarding IL-6, particularly in the context of immune regulation and diseases like Crohn's disease:\n", "\n", - "1. **Biological Function:**\n", - " - IL-6 is a cytokine that plays a crucial role in immune regulation. It is involved in the inflammatory response and is essential for the body's defense against infections and injuries.\n", + "1. **Biological Function**: IL-6 is a cytokine that plays a critical role in the immune system. It is involved in the regulation of immune responses, inflammation, and hematopoiesis. IL-6 is an important mediator in the body's response to infections and tissue injuries, helping to stimulate immune response.\n", "\n", - "2. **Role in Pathways:**\n", - " - IL-6 signaling can occur through two main pathways:\n", - " - **Classical Pathway:** This involves the membrane-bound IL-6 receptor (IL-6Rα) where IL-6 binds to IL-6Rα, forming a complex that recruits a membrane-bound gp130 coreceptor, triggering downstream signaling cascades.\n", - " - **Trans-signaling Pathway:** This involves the soluble IL-6 receptor (sIL-6Rα). The IL-6/sIL-6Rα complex can associate with gp130 to initiate signaling in cells that do not express the membrane-bound IL-6Rα. This pathway is particularly important in inflammatory diseases.\n", + "2. **Role in Pathways**: IL-6 signaling occurs via two main pathways:\n", + " - The classical pathway, mediated by the membrane-bound IL-6 receptor (IL-6Rα), which interacts with IL-6 to initiate signaling.\n", + " - The trans-signaling pathway, which involves the soluble IL-6 receptor (sIL-6Rα). In this pathway, the IL-6/sIL-6Rα complex can bind to the gp130 membrane-bound receptor to form an active signaling complex that initiates further downstream effects, such as the activation of Janus kinase (Jak) family proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation.\n", "\n", - "3. **Interactions with Other Molecules:**\n", - " - IL-6 interacts with IL-6Rα and gp130 to form a receptor complex that activates intracellular signaling pathways.\n", - " - It leads to the phosphorylation of Janus kinase (Jak) family proteins and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3), which are critical for transmitting the signal inside the cell.\n", + "3. **Interactions with Other Molecules**: IL-6 interacts with both its membrane-bound and soluble receptors (IL-6Rα and sIL-6Rα) to form complexes that recruit gp130, leading to signal transduction. The interaction with gp130 is crucial as it leads to the formation of an active hexameric receptor complex which drives further signaling processes.\n", "\n", - "4. **Importance in the Biological System Being Modeled:**\n", - " - In the context of Crohn's disease, IL-6 contributes to enhanced T-cell survival and resistance to apoptosis in the lamina propria, along with elevated chemokine secretion. This makes it a significant player in the disease's pathology.\n", - " - The study of IL-6 and its pathways is crucial in understanding its role in diseases such as Crohn's disease and rheumatoid arthritis, and in developing therapeutic interventions targeting IL-6 signaling.\n", + "4. **Importance in Biological Systems**: IL-6 is particularly significant in the pathology of inflammatory diseases, such as Crohn's disease. It contributes to enhanced T-cell survival and apoptosis resistance, as well as elevated chemokine secretion in the intestinal mucosa and peripheral blood. This makes IL-6 signaling a critical target for therapeutic interventions in such conditions.\n", "\n", - "Overall, IL-6 is an important cytokine with significant roles in immune response and inflammation, making it a key target for research in immune-mediated diseases.\n", + "In summary, IL-6 is a multifunctional cytokine with essential roles in immune regulation and inflammatory responses, especially relevant to conditions like Crohn’s disease. Its ability to signal through multiple pathways and interact with various molecular complexes underscores its importance in maintaining immune homeostasis and its potential as a therapeutic target.\n", "\n", "================================================================================\n", "17. R_IL6 (ID: mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83)\n", "================================================================================\n", - "Based on the context provided, there is no specific mention of a species named 'R_IL6'. However, based on the context and related molecules mentioned, it is possible to infer some insights into what 'R_IL6' might relate to.\n", - "\n", - "### Biological Function:\n", - "- **IL-6:** IL-6 (Interleukin-6) is a cytokine involved in immune response, inflammation, and hematopoiesis. It plays a significant role in the body's defense mechanisms and is implicated in various diseases when dysregulated.\n", + "The provided context does not explicitly detail the species 'R_IL6' with the specified ID. However, based on the information present and general biological knowledge, 'R_IL6' could potentially represent a receptor or related component involved in the Interleukin-6 (IL-6) signaling pathway.\n", "\n", - "### Role in Pathways:\n", - "- **IL-6 Signaling Pathway:** This pathway involves the binding of IL-6 to its receptor, IL-6R, and generally leads to the activation of JAK/STAT signaling pathways. This signaling can induce transcription and various immune responses.\n", + "### General Knowledge Inference for 'R_IL6':\n", + "1. **Biological Function**: \n", + " - IL-6 is a cytokine that plays a critical role in immune response, inflammation, and hematopoiesis. It typically signals through a receptor complex that may include the IL-6 receptor (IL-6R) and a signal transducer such as gp130.\n", + " - The designation 'R_IL6' suggests it may be an IL-6 receptor component, involved in binding IL-6 and initiating downstream signaling pathways.\n", "\n", - "### Interactions with Other Molecules:\n", - "- **IL-6R and sIL-6R (soluble IL-6 receptor):** The IL-6 signaling requires the complex formation of IL-6 with its receptor IL-6R, including its soluble form sIL-6R. This complex can further bind to another molecule, gp130 (glycoprotein 130), which is necessary for signal transduction.\n", - "- **STAT3:** The context mentions pSTAT3 signaling, indicating that IL-6 signaling involves phosphorylation of STAT3, a transcription factor that mediates various gene expressions in response to IL-6.\n", + "2. **Role in Pathways**:\n", + " - IL-6 signaling involves the activation of the Janus kinase (Jak) and Signal Transducer and Activator of Transcription 3 (STAT3) pathway. Binding of IL-6 to its receptor complex activates these pathways, leading to the transcription of genes involved in inflammatory and immune responses.\n", + " - The context also mentions \"Classical\" and \"Trans\" pathways, suggesting classical signaling involves membrane-bound IL-6R, while trans-signaling involves soluble IL-6R (sIL-6R).\n", "\n", - "### Importance in the Biological System Being Modeled:\n", - "- **Regulation and Modeling:** IL-6 is involved in the regulation of immune processes, and its signaling is crucial in understanding conditions like Crohn's disease or rheumatoid arthritis. The context mentions modeling efforts and pharmacokinetic analyses suggesting a focus on IL-6 and its receptor interactions.\n", - "- **Treatment Implications:** The modeling discussed, such as the dose-response characteristics, indicates IL-6's importance in therapeutic frameworks, potentially focusing on disorders with immune dysregulation.\n", + "3. **Interactions with Other Molecules**:\n", + " - IL-6 interacts with both its membrane-bound and soluble forms of IL-6R, which facilitates different signaling outcomes.\n", + " - Interaction with sIL-6R allows IL-6 to signal in cells that do not express membrane-bound IL-6R by associating with the ubiquitously expressed signal transducer, gp130.\n", + " - The term 'R_IL6' within a complex might specifically denote its interaction with these molecules in such pathways.\n", "\n", - "### Potential Inference for 'R_IL6':\n", - "- While there is no direct mention of 'R_IL6', it could potentially refer to a variant, receptor, or complex of IL-6 involved in signaling pathways. It might be modeled similarly in studies related to immune regulation or therapeutic targeting. Given the context, it is likely associated with IL-6's complex pathways and interactions within the immune system.\n", + "4. **Importance in the Biological System**:\n", + " - IL-6 signaling is crucial for immune regulation and has been implicated in several inflammatory diseases such as Crohn’s disease and rheumatoid arthritis.\n", + " - Modulating IL-6 activity, often through its receptor interactions, is a therapeutic target for reducing chronic inflammation and autoimmune diseases.\n", "\n", - "In summary, 'R_IL6' could be a component related to IL-6 signaling, likely significant in immune system modeling and therapeutic interventions.\n", + "Overall, while the specific role of 'R_IL6' is not detailed in the provided text, understanding its potential place within IL-6 signaling pathways offers insights into its biological significance and therapeutic relevance.\n", "\n", "================================================================================\n", "18. Ractive (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb)\n", "================================================================================\n", - "The context provided does not include specific information about a species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). However, I can provide inferential information based on the general context described, which involves IL-6 signaling and therapeutic interventions in conditions like rheumatoid arthritis and Crohn’s disease.\n", + "The provided context does not contain specific information about the species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). The text focuses primarily on the IL-6 signaling pathway, its associated components, and the effects of targeting this pathway with therapeutic antibodies such as anti-IL-6 and anti-IL-6Rα, particularly in the context of autoimmune diseases like Crohn's Disease and rheumatoid arthritis.\n", "\n", - "1. **Biological Function:**\n", - " - Although 'Ractive' is not directly mentioned, within the context of an immune regulation framework, it could be hypothesized that 'Ractive' might represent a molecule involved in the immune response or signal transduction, perhaps similar to interleukins or receptors.\n", + "Since there is no direct mention of 'Ractive' in the context, we can infer its nature based on the general themes discussed:\n", "\n", - "2. **Role in Pathways:**\n", - " - Considering the IL-6 signaling pathway is a focal point of the study, 'Ractive' might play a role similar to elements of the IL-6 signaling cascade. This could involve participation in cytokine signaling or acting as a receptor or receptor complex, similar to IL-6 or its soluble receptor counterparts.\n", + "1. **Biological Function & Role in Pathways**: Given the context's focus on the IL-6 pathway, Ractive might be hypothesized as a molecule related to cytokine signaling, possibly a receptor, a part of a signaling cascade, or even an associated regulatory protein modulating immune responses.\n", "\n", - "3. **Interactions with Other Molecules:**\n", - " - 'Ractive' might engage in interactions akin to the IL-6 and its soluble receptor interactions. Such molecules often form complexes that could be potential targets for therapeutic antibodies or other modulators, a common approach in autoimmune conditions like those discussed.\n", + "2. **Interactions with Other Molecules**: In a systems biology model of immune regulation, Ractive might interact with cytokines (like IL-6), receptors (such as IL-6Rα), or downstream signaling molecules (e.g., STAT proteins). Its interactions would be crucial for understanding the dynamics of the immune response.\n", "\n", - "4. **Importance in the Biological System:**\n", - " - If 'Ractive' partakes in a pathway analogous to IL-6 signaling, it could be crucial in mediating inflammatory responses, playing a part in disease progression or resolution, and thus presenting itself as a possible target for therapeutic intervention.\n", + "3. **Importance in the Biological System**: If Ractive is indeed involved in the IL-6 mediated pathway, it would be important for modulating immune responses, potentially influencing inflammation and immune system activity, which are critical in conditions like Crohn’s Disease.\n", "\n", - "Without specific information on 'Ractive' from the text, these interpretations are speculative and should be considered within the broader context of known signaling pathways and therapeutic targets discussed in the study.\n", + "In the absence of context-specific information about 'Ractive', it is important to consult the original source documents or related scientific literature for precise insights into this species’ characteristics and role within the biological system being modeled.\n", "\n", "================================================================================\n", "19. STAT3 (ID: mw42054cd7_17af_46da_970c_7f99151906ad)\n", "================================================================================\n", - "Based on the provided context and general knowledge:\n", + "Based on the provided context and general knowledge, here is the background information about STAT3:\n", + "\n", + "### General Background on STAT3:\n", + "STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that is pivotal in transmitting signals from the cell surface to the nucleus. It is part of the STAT protein family and is involved in cellular processes such as cell growth and apoptosis.\n", "\n", - "### Biological Function of STAT3\n", - "STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor activated by phosphorylation. It is a key player in transmitting signals from various cytokines and growth factors to the cell nucleus, where it modifies gene expression. STAT3 is critical for regulating numerous biological processes, including cell growth, apoptosis, and immune response.\n", + "### Biological Function:\n", + "STAT3 is primarily activated through phosphorylation—a process in which a phosphate group is added, often leading to a functional change of the protein. Once phosphorylated (pSTAT3), it dimerizes and translocates to the nucleus where it can influence the expression of a variety of genes.\n", "\n", - "### Role in Pathways\n", - "STAT3 is involved in the JAK-STAT signaling pathway. Upon activation, typically by cytokines such as IL-6, STAT3 is phosphorylated by associated Janus kinases (JAKs), dimerizes, and translocates to the nucleus. In this context, STAT3 appears integral to the IL-6 signaling pathway, which is involved in various cellular responses, including inflammation, immune function, and acute-phase reactions.\n", + "### Role in Pathways:\n", + "STAT3 is a critical component of the JAK-STAT signaling pathway, which is a chain of interactions between proteins in a cell, and is also involved in mediating responses to cytokines and growth factors. In this context, it appears specifically related to IL-6 signaling. IL-6 is a cytokine that can induce the phosphorylation of STAT3, leading to its activation and subsequent gene transcription that drives processes like differentiation of lymphocytes and expression of acute-phase proteins such as C-reactive protein (CRP).\n", "\n", - "### Interactions with Other Molecules\n", - "Within the IL-6 signaling pathway, STAT3 interacts with molecules such as the IL-6 receptor (IL-6R), gp130, and soluble forms of these receptors (sIL-6R and sgp130). The phosphorylation of STAT3 (pSTAT3) indicates its activation and subsequent transcriptional regulation of target genes.\n", + "### Interactions with Other Molecules:\n", + "STAT3 interacts with various molecules primarily through the phosphorylation process. It is closely tied to components like gp130 and sIL-6R in the IL-6 signaling cascade. In response to IL-6, the receptor complex that includes IL-6Rα and gp130 becomes activated, leading to JAK activation and subsequent phosphorylation of STAT3.\n", "\n", - "### Importance in Biological Systems\n", - "STAT3 plays a significant role in mediating the effects of cytokines like IL-6, which are crucial in immune responses and inflammation. The context mentions disease models such as Crohn's disease, where increased activation of STAT3 (pSTAT3) in tissues is noted, highlighting its potential role in the disease's inflammatory processes. This suggests that STAT3's regulation is pivotal in understanding and developing therapeutic approaches for immune and inflammatory disorders.\n", + "### Importance in Biological Model:\n", + "Within the context of the provided information, STAT3 plays a significant role in diseases such as Crohn's disease, where its phosphorylated form, pSTAT3, has been observed in colon biopsies. This suggests that STAT3 might be central to inflammatory signaling pathways that underpin certain diseases, making it a potential target for therapeutic interventions.\n", "\n", - "In summary, STAT3 is a central molecule in cytokine signaling pathways that influence immune function and inflammation, making it a critical target for studying diseases characterized by dysregulated immune responses, such as Crohn's disease.\n", + "This inferred understanding aligns with its general role in bodily immunity and inflammation, highlighting its potential implications in both research and clinical settings relevant to cytokine signaling and immune response regulation.\n", "\n", "================================================================================\n", "20. pSTAT3 (ID: mw39c2e431_fdc3_4964_be29_6ca856620b1b)\n", "================================================================================\n", - "The context provided mainly revolves around the IL-6 signaling pathway and its components, such as IL-6Rα, gp130, sIL-6Rα, sgp130, and CRP, with sporadic mentions of STAT3 and pSTAT3. Here’s a summary focused on pSTAT3 based on the document and broader biological knowledge:\n", + "Based on the provided context and general knowledge, here's an overview of pSTAT3:\n", "\n", - "### pSTAT3 Biological Function\n", - "- **pSTAT3** refers to the phosphorylated form of STAT3 (Signal Transducer and Activator of Transcription 3).\n", - "- STAT3 is a transcription factor activated in response to cytokines like IL-6.\n", - "- When phosphorylated, STAT3 dimerizes and translocates to the nucleus to regulate the expression of target genes.\n", + "### Biological Function:\n", + "- pSTAT3, or phosphorylated STAT3, is part of the STAT (Signal Transducer and Activator of Transcription) family of transcription factors. These proteins are crucial for relaying information from extracellular signals to the cell nucleus, where they influence gene expression.\n", + "- Upon activation, STAT3 becomes phosphorylated, hence pSTAT3, which allows it to dimerize (pair with another STAT3 molecule), translocate to the nucleus, and bind to DNA, promoting the transcription of target genes.\n", "\n", - "### Role in Pathways\n", - "- **IL-6 Signaling**: pSTAT3 is a critical component of the IL-6 signaling pathway. The binding of IL-6 to its receptor leads to the activation of the JAK kinases, which in turn phosphorylate STAT3.\n", - "- **Gene Expression**: pSTAT3 influences the transcription of various genes involved in immune responses, cell survival, and proliferation.\n", + "### Role in Pathways:\n", + "- pSTAT3 is instrumental in the IL-6 signaling pathway. IL-6 is a cytokine that, upon binding to its receptors, activates the Janus kinase (Jak) pathway, which in turn phosphorylates STAT3.\n", + "- The context describes a trans-signaling pathway involving IL-6 and its soluble receptor sIL-6Rα, with pSTAT3 being a downstream effector of this pathway.\n", + "- This pathway is crucial for various cellular responses, including differentiation, survival, and proliferation, especially in immune and inflammatory responses.\n", "\n", - "### Interactions with Other Molecules\n", - "- **IL-6 and sIL-6Rα**: The context describes the significance of trans-signaling mediated by IL-6 and its soluble receptor forms, which lead to STAT3 phosphorylation.\n", - "- **gp130**: This coreceptor is crucial for the activation of STAT3. It binds the IL-6/sIL-6R complex leading to STAT3 phosphorylation.\n", - "- **CRP and other gene products**: The activation of STAT3 can influence the expression of C-reactive protein and other acute-phase proteins.\n", + "### Interactions with Other Molecules:\n", + "- The phosphorylation of STAT3 is a result of interactions with upstream kinases like Jak, following cytokine receptor activation (e.g., by IL-6/sIL-6Rα).\n", + "- pSTAT3 is known to interact with various co-factors and DNA sequences to regulate the expression of genes involved in inflammation and immune responses.\n", + "- It is hinted that pSTAT3 levels are elevated in inflammatory conditions like Crohn’s disease, indicating interactions with molecules or pathways involved in inflammation.\n", "\n", - "### Importance in the Biological System\n", - "- **Pathological Conditions**: The document mentions increased pSTAT3 levels in colon biopsies in the context of Crohn’s disease, suggesting its role in inflammatory bowel diseases.\n", - "- **Biological Significance**: Being a part of the IL-6 signaling pathway, pSTAT3 is important in mediating immune responses and might have implications in various diseases due to dysregulated cytokine signaling.\n", + "### Importance in the Biological System:\n", + "- pSTAT3 is a critical mediator in the context of inflammatory diseases, such as Crohn’s disease, where its increased levels in colon biopsies suggest a role in the pathogenesis or progression of these diseases.\n", + "- By regulating gene expression in response to cytokine signaling, STAT3, especially in its phosphorylated form, is important for maintaining appropriate immune responses and cellular homeostasis.\n", + "- Its role extends beyond normal physiology to pathophysiological conditions, where its dysregulation is often linked to chronic inflammatory states, autoimmune disorders, and even cancers.\n", "\n", - "In summary, pSTAT3 is a pivotal signaling molecule involved in transcriptional regulation, primarily within the IL-6-mediated pathway. Its phosphorylation status determines its activity, which can impact various biological processes and contributes to disease states such as inflammatory bowel disease.\n", + "In summary, pSTAT3 is a pivotal molecule within the IL-6 cytokine signaling pathway, acting as a key transcriptional regulator in immune and inflammatory responses. Its heightened activity is associated with pathological conditions, highlighting its importance as a potential therapeutic target in such diseases.\n", "\n", "================================================================================\n", "21. CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mwd5313618_89eb_4c8c_bc82_66f10f966349)\n", "================================================================================\n", - "The species referred to as \"CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\" in the provided context likely represents C-reactive protein (CRP), based on the common abbreviation for C-reactive protein. Here is a summary of the relevant background information regarding CRP:\n", + "Based on the context provided, here is the background information about the species 'CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)':\n", "\n", - "1. **Biological Function:**\n", - " - CRP is an acute-phase protein produced by the liver in response to inflammation. Its primary function is to bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system via C1q.\n", + "1. **Biological Function**: CRP, or C-reactive protein, is a biomarker of inflammation in the body. It is produced by the liver in response to inflammation and its levels increase in the bloodstream during inflammatory processes.\n", "\n", - "2. **Role in Pathways:**\n", - " - CRP is often used as a clinical biomarker for inflammation. It plays a significant role in the pathway of immune response, particularly in recognizing and promoting the clearance of pathogens and damaged cells, thereby serving as a marker of inflammation and immune system activation.\n", - " - In the context of the simulation model discussed, changes in CRP levels can indicate the effectiveness of drug treatments targeting the IL-6 signaling pathway, as CRP levels are a downstream effect of cytokine signaling, particularly IL-6.\n", + "2. **Role in Pathways**: CRP is primarily associated with the body's immune response to inflammation. It is part of the acute phase response, which is a rapid systemic response to injury, infection, or other inflammatory stimuli. The context suggests that CRP is being used in a model to evaluate inflammation levels, particularly in relation to Crohn’s disease and the effects of anti-inflammatory drugs like tocilizumab.\n", "\n", - "3. **Interactions with Other Molecules:**\n", - " - CRP interacts with various components of the immune system such as the complement system. It works closely with interleukin-6 (IL-6), as IL-6 is a major inducer of CRP synthesis in the liver.\n", - " - The context mentions interactions with drugs such as anti-IL-6Rα antibodies, which suggests that CRP levels are used to measure the impact of these treatments on inflammation levels in diseases like Crohn's disease.\n", + "3. **Interactions with Other Molecules**: CRP interacts with various components of the immune system. In the context of the document, CRP levels are used to assess the effectiveness of inhibiting IL-6 signaling—a cytokine involved in inflammation by targeting IL-6 or its receptors. Thus, CRP serves as an indicator for the efficacy of this anti-inflammatory strategy.\n", "\n", - "4. **Importance in the Biological System Being Modeled:**\n", - " - Within the modeled system (as described in the context), CRP serves as a critical marker for inflammation, allowing researchers to predict the impact of various treatment strategies on inflammatory diseases like Crohn's disease.\n", - " - The model’s ability to predict changes in CRP levels helps in studying the effects of perturbations through different therapeutic approaches aimed at inhibiting the IL-6 signaling pathway.\n", + "4. **Importance in the Biological System Being Modeled**: In the model described, CRP is a critical marker used to validate and predict the outcomes of drug treatments aimed at reducing inflammation, such as those used in Crohn's disease. The model uses CRP as a metric to evaluate the suppression of inflammation due to the therapeutic inhibition of IL-6 signaling pathways.\n", "\n", - "Overall, CRP is an important indicator of inflammation and is crucial in the validation and assessment of disease models involving inflammatory processes, such as those involving IL-6 signaling.\n", + "In summary, CRP is an important inflammatory marker used in the modeling of immune response and drug efficacy in inflammatory diseases, particularly for evaluating interventions targeting IL-6 signaling.\n", "\n", "================================================================================\n", "22. sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw2e464cf3_a09c_4b7c_9f3c_06720016a48e)\n", "================================================================================\n", - "Based on the provided context, specific information about the species 'sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned. However, inferring from the general context of the documents, which involve molecular interactions and pathways related to the IL-6 signaling system, the following insights can be suggested:\n", + "From the context provided, it seems that the specific species 'sR' (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) is not directly mentioned or detailed. Thus, I will infer its possible role based on the general context involving related biological components.\n", "\n", - "1. **Biological Function**:\n", - " - The 'sR' component is likely a part of the IL-6 signaling pathway. In similar contexts, 'sR' often denotes soluble receptors. Soluble receptors can modulate the activity of their respective cytokines or hormones by binding to them and altering their bioavailability or impacting downstream signaling pathways.\n", + "1. **Biological Function:**\n", + " - Given the surrounding context of interleukin 6 (IL-6), it is likely that 'sR' refers to a soluble receptor, potentially the soluble IL-6 receptor (sIL-6R). Soluble receptors often function to sequester ligands or modulate signaling pathways by facilitating ligand interaction with cell surface receptors.\n", "\n", - "2. **Role in Pathways**:\n", - " - Considering the IL-6 pathway is mentioned, the 'sR' species might function in the classical signaling or trans-signaling pathways of IL-6. In these pathways, soluble receptors either enhance or inhibit signal transduction, impacting gene expression mediated by factors like STAT3.\n", + "2. **Role in Pathways:**\n", + " - 'sR', if it represents sIL-6R, participates in the IL-6 signaling pathways. IL-6 can bind to sIL-6R, forming a complex that further associates with membrane-bound gp130, leading to activation of intracellular signaling pathways such as the JAK/STAT pathway. This pathway is involved in inflammation and the regulation of the immune response.\n", "\n", - "3. **Interactions with Other Molecules**:\n", - " - The context suggests interaction with the IL-6 cytokine, as soluble IL-6 receptors (e.g., sIL-6R) bind IL-6, forming a complex (IL-6:sR) that may interact with other receptor components, such as gp130, to elicit a cellular response. These interactions are crucial for regulating inflammatory responses and immune function.\n", + "3. **Interactions with Other Molecules:**\n", + " - 'sR' forms part of the IL-6/sIL-6R complex interacting with gp130, a common receptor subunit involved in IL-6 family cytokine signaling. This complex formation enhances signaling across various tissues, especially when the IL-6 concentration is limited, as seen from the content discussing IL-6 and sgp130 concentrations.\n", "\n", - "4. **Importance in the Biological System Being Modeled**:\n", - " - Soluble receptors are significant in maintaining homeostasis and regulating the intensity of cytokine signaling. The modeling aspect suggests that understanding the dynamic balance of these components (like sgp130, mentioned in the document) is crucial for accurately predicting system behavior under various conditions and treatments, especially targeting IL-6 or its receptors.\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - If 'sR' represents a soluble receptor interacting with IL-6, it plays a crucial role in modulating IL-6's effects, potentially affecting processes like acute-phase responses, immune function, and inflammation. The model suggests that perturbations in components like sgp130 have minor effects due to concentration differences, implying that the effective modulation of signaling depends heavily on components like sR/sIL-6R and IL-6 interactions.\n", "\n", - "In summary, 'sR' in this context is likely a soluble receptor involved in the IL-6 signaling pathway, influencing immune responses by modulating cytokine availability and activity.\n", + "In summary, while 'sR' is not explicitly described, it might denote a molecule like the soluble IL-6 receptor within the context of IL-6 signaling pathways, influencing inflammatory and immune responses.\n", "\n", "================================================================================\n", "23. CRPExtracellular (ID: mw36ea78c1_ed71_4def_96d3_857a442d7195)\n", "================================================================================\n", - "The species named 'CRPExtracellular' likely refers to the extracellular form of C-reactive protein (CRP), a well-known biomarker and acute-phase protein in various biological systems, particularly in the context of inflammation.\n", + "Based on the provided context, it seems that specific information about the species 'CRPExtracellular' (ID: mw36ea78c1_ed71_4def_96d3_857a442d7195) within the context of mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e is not explicitly detailed. However, we can infer some information based on the general role of C-reactive protein (CRP) within biological systems and its mention in the context.\n", "\n", - "### Biological Function\n", - "C-reactive protein (CRP) is produced by the liver in response to inflammation. It is an acute-phase protein that plays a critical role in the host's defense mechanism. CRP is part of the innate immune system as it binds to the surface of dead or dying cells and certain bacteria to activate the complement system, promoting phagocytosis by macrophages.\n", + "1. **Biological Function**: CRP, or C-reactive protein, is a substance produced by the liver in response to inflammation. Its primary function is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via the C1Q complex, thus playing an important role in the body's immune response by enhancing the ability to clear pathogens and damaged cells.\n", "\n", - "### Role in Pathways\n", - "In the context of the provided documents, CRP is linked to the IL-6 signaling pathway. IL-6 is a cytokine that stimulates the production of CRP in the liver. The IL-6 mediated pathway contributes to inflammatory responses, and CRP serves as a downstream marker for inflammation. The model mentioned explores strategies to treat Crohn's disease by inhibiting IL-6 signaling, which suggests a modulation of CRP levels.\n", + "2. **Role in Pathways**: CRP is typically involved in the acute phase response to inflammation. Its production increases in response to pro-inflammatory cytokines like interleukin-6 (IL-6), as indicated by the context mentioning IL-6 and CRP in relation to various treatments aiming to modulate inflammation pathways.\n", "\n", - "### Interactions with Other Molecules\n", - "CRP interacts with various molecules and systems in the body:\n", - "- It binds to phosphocholine on the surface of dead cells and some types of bacteria.\n", - "- CRP activates the complement system, which enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells.\n", - "- CRP levels are used to assess the extent of inflammation in response to stimuli like IL-6, another cytokine involved in the body's inflammatory response.\n", + "3. **Interactions with Other Molecules**: The interaction between CRP and IL-6 is highlighted, with IL-6 being a key cytokine that stimulates the production of CRP. The context also discusses various treatment strategies that involve targeting IL-6 or its receptors to reduce inflammation and subsequently decrease CRP levels, demonstrating CRP's role as a marker for inflammatory activity and the effectiveness of anti-inflammatory treatments.\n", "\n", - "### Importance in the Biological System Being Modeled\n", - "In the biological model presented in the documents, CRP serves as a critical biomarker to evaluate the efficacy of therapeutic strategies targeting IL-6 signaling in inflammatory diseases like Crohn's disease. The documents emphasize the model's capacity to predict the response of CRP levels to different treatment strategies, validating the trained model against clinical trial data. Suppression of CRP is an indicator of effective inhibition of inflammation, showcasing the importance of CRP measurement in assessing the success of interventions aimed at controlling inflammatory pathways.\n", + "4. **Importance in the Biological System Being Modeled**: The context suggests that CRP is used as a biomarker for inflammation in Crohn’s disease, and its levels are used to monitor the effectiveness of treatment strategies that target IL-6 signaling. Therefore, CRP is a key output in the model being discussed, representing the systemic inflammatory response and providing feedback on the effectiveness of therapeutic interventions.\n", "\n", - "In summary, CRPExtracellular represents the extracellular C-reactive protein operating as a biomarker for inflammation, influenced by IL-6 signaling pathways, and significant in evaluating treatment efficacy for diseases characterized by chronic inflammation.\n", + "In conclusion, while specific details about the species 'CRPExtracellular' in the mentioned context are not given, its role as a marker of inflammation and its regulation through pathways involving IL-6 are central to the model's focus on understanding and predicting the outcomes of therapeutic interventions in inflammatory conditions like Crohn’s disease.\n", "\n", "================================================================================\n", "24. sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw147d30ec_478e_4090_b496_128a131d29eb)\n", "================================================================================\n", - "The species referred to as 'sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' appears to be a protein known as sgp130 located in a specific biological context (ID: mw147d30ec_478e_4090_b496_128a131d29eb). Here is a summary of the relevant background information:\n", + "Based on the provided context, the species labeled as 'sgp130' (associated with ID: mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e) seems to be a fusion protein designed to interact with components involved in IL-6 signaling pathways. Here's a summary of its relevant aspects:\n", "\n", - "1. **Biological Function**: \n", - " sgp130 is a soluble form of gp130, which is a component of the IL-6 receptor complex. sgp130 acts by binding to the IL-6/sIL-6Rα complex, thereby inhibiting IL-6 trans-signaling. This function is crucial as IL-6 trans-signaling is associated with various inflammatory and autoimmune conditions.\n", + "- **Biological Function:**\n", + " - sgp130 functions as an inhibitor of IL-6 trans-signaling. It is a fusion protein that combines the extracellular portion of gp130 with the Fc region of human IgG1, termed sgp130Fc. This modification allows sgp130 to bind to the IL-6/sIL-6Rα complex.\n", "\n", - "2. **Role in Pathways**:\n", - " sgp130 plays a role in the IL-6 signaling pathway by inhibiting the formation of active signaling complexes. This modulation of the pathway can potentially reduce inflammatory responses mediated through IL-6 trans-signaling.\n", + "- **Role in Pathways:**\n", + " - It is involved in the IL-6 trans-signaling pathway. IL-6 is a cytokine that plays a crucial role in immune response and inflammation. The trans-signaling pathway involves the binding of IL-6 to a soluble receptor sIL-6Rα, which then associates with gp130 to signal.\n", "\n", - "3. **Interactions with Other Molecules**:\n", - " sgp130 interacts specifically with the complex formed by IL-6 and its soluble receptor sIL-6Rα. By binding to this complex, sgp130 prevents the subsequent interaction with the membrane-bound gp130, effectively blocking signal transduction.\n", + "- **Interactions with Other Molecules:**\n", + " - sgp130 interacts specifically with the IL-6/sIL-6Rα complex. The context suggests that sgp130 binds this complex with similar affinity to natural gp130, aiming to inhibit downstream signaling events such as CRP (C-reactive protein) and pSTAT3 production in the gut.\n", "\n", - "4. **Importance in the Biological System Being Modeled**:\n", - " In the context of therapeutic applications, particularly for conditions such as Crohn's disease, sgp130 is evaluated for its potential use in inhibiting inflammatory signaling. Despite being present in large concentrations compared to IL-6, sensitivity analyses suggest that the therapeutic effectiveness of sgp130-based interventions may require very high doses due to its minimal impact on overall system dynamics at typical concentrations. This is because sgp130 naturally exists in excess relative to IL-6, limiting its impact when used in moderate amounts.\n", - "\n", - "5. **Relevance in Systems Biology Model**:\n", - " The systems biology model suggests that while sgp130 has a role, its overall impact on key output parameters (such as CRP levels) is limited unless used in substantial amounts. It highlights the need for potentially better therapeutic targets like IL-6 and sIL-6Rα, where alterations could more significantly affect system outputs.\n", + "- **Importance in the Biological System:**\n", + " - Despite its designed purpose, simulations and sensitivity analyses indicate that sgp130 (as sgp130Fc) has relatively low impact on the biological system being modeled, particularly when used as a therapeutic agent for conditions like Crohn’s disease. Its effectiveness is noted only at very high and frequent doses due to the high baseline levels of sgp130 naturally present, in contrast to the low concentration of IL-6.\n", "\n", - "Overall, sgp130 serves a regulatory function in IL-6 mediated signaling, highlighting its role in inflammatory pathways but with suggested limitations for therapeutic application based on the systems biology model being considered.\n", + "In summary, sgp130 is primarily modeled to inhibit IL-6 trans-signaling but poses challenges as a therapeutic due to its excess presence compared to IL-6, limiting its potential impact on the system without large dosage increases.\n", "\n", "================================================================================\n", "25. sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mwab41493c_6349_45f1_a226_3030cfed0e06)\n", "================================================================================\n", - "Based on the provided context, the species 'sR_IL6_sgp130', identified by the ID mwab41493c_6349_45f1_a226_3030cfed0e06, appears to be related to a fusion protein that plays a role in inhibiting IL-6 trans-signaling pathways. This fusion protein, popularly referred to as sgp130Fc, combines the extracellular portion of glycoprotein 130 (gp130) with the Fc region of human IgG1. \n", + "Based on the context provided, specific mentions of the species named 'sR_IL6_sgp130' (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) are not directly available. However, we can infer its nature and potential role based on the information about similar molecules provided in the document.\n", "\n", - "**Biological Function:**\n", - "sR_IL6_sgp130 acts to bind specifically to the IL-6/sIL-6Rα complex, which is pivotal in mediating IL-6 trans-signaling. By binding to this complex, it effectively prevents the signaling process that would typically activate downstream pathways, such as the phosphorylation of STAT3 (pSTAT3) and subsequent gene transcription.\n", + "1. **Biological Function**: The context discusses sgp130, which is known to be a soluble form of the gp130 receptor. These soluble receptors, like sgp130, are known to inhibit IL-6 trans-signaling. In general, soluble receptors can bind cytokines or cytokine complexes in the extracellular environment, preventing them from triggering cell surface receptors and subsequent intracellular signaling cascades.\n", "\n", - "**Role in Pathways:**\n", - "Its primary role resides in the inhibition of IL-6 trans-signaling, which is critical in the context of inflammatory responses and diseases like Crohn’s disease. The simulations and models cited suggest that this species is involved in modifying the dose-response relationship of certain therapeutic interventions, leading to outcomes like CRP suppression.\n", + "2. **Role in Pathways**: The sgp130 serves as an inhibitor in the IL-6 signaling pathway, particularly in IL-6 trans-signaling. This pathway is involved in various inflammatory and immune processes. By inhibiting this pathway, sgp130 could potentially reduce inflammatory responses, which is particularly relevant in conditions like Crohn’s disease, as mentioned in the context.\n", "\n", - "**Interactions with Other Molecules:**\n", - "sR_IL6_sgp130 interacts predominantly with the IL-6/sIL-6Rα complex. The sgp130 component has a high affinity for this complex, which is a major interaction through which it achieves its inhibitory functions.\n", + "3. **Interactions with Other Molecules**: The sgp130 binds to the IL-6/sIL-6Rα complex. This specific interaction is crucial for its role as an inhibitor in the pathway. It prevents the IL-6 complex from interacting with membrane-bound gp130, thus blocking downstream signaling events.\n", "\n", - "**Importance in the Biological System Being Modeled:**\n", - "In the system, while sR_IL6_sgp130 is present in high baseline levels and exerts limited effects on steady-state system dynamics due to its excess relative to free IL-6 concentrations, it remains a pivotal molecule for therapeutic applications. Its primary importance lies in its use as a potential therapeutic intervention, especially considered for conditions with elevated IL-6 trans-signaling, requiring very high and frequent doses to be effective due to its baseline levels.\n", + "4. **Importance in the Biological System Being Modeled**: In the biological system modeled, sgp130 appears to represent a regulatory component that modulates the IL-6 signaling pathway. Its presence in high baseline levels as compared to free IL-6 indicates a natural buffering or regulatory role in maintaining homeostasis in the signaling environment. It suggests that significant therapeutic modulation (e.g., large doses of sgp130Fc) would be needed to observe pronounced effects.\n", "\n", - "This summary indicates that sR_IL6_sgp130 is critical in the context of therapies aiming to modulate IL-6 signaling pathways, providing insights into the need for precise dosing strategies to achieve therapeutic benefits.\n", + "While specific details about 'sR_IL6_sgp130' (#2) are not available, the understanding of sgp130's role in IL-6 trans-signaling and its functional characterization can be reasonably extrapolated to gain insights into this species' potential biological importance.\n", "\n", "================================================================================\n", "26. Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mwf405687b_7401_44ec_a0d6_4a2b35c13e8a)\n", "================================================================================\n", - "Based on the provided context, no specific information about the species named 'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' was found in the excerpts from the document. However, I can infer some potential characteristics and roles it might have based on general biological knowledge and the information typically associated with similar components.\n", + "The context provided does not contain specific information about the biological species or molecule named 'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' or its ID 'mwf405687b_7401_44ec_a0d6_4a2b35c13e8a'. Given the lack of direct details in the documents, I can infer potential characteristics of 'Ab_sR' based on common biological concepts and patterns discussed in similar contexts.\n", "\n", - "1. **Biological Function**: Generally, \"Ab\" in a biological context often refers to antibodies. If 'Ab_sR' is indeed an antibody or related to antibody activity, its function could be to bind to specific antigens, perhaps part of a signaling pathway or immune response mechanism.\n", + "1. **Biological Function**: Given the use of \"Ab\" in the name, 'Ab_sR' may refer to an antibody-related species, possibly a soluble receptor (sR) or an antibody-receptor complex. In many biological systems, antibodies play crucial roles in immune responses, binding to specific antigens to neutralize them or mark them for destruction by other immune cells.\n", "\n", - "2. **Role in Pathways**: The context mentions IL-6 and its receptor interactions, which are part of immune signaling pathways. If 'Ab_sR' is interacting with such pathways, it could be modulating or inhibiting specific signals, particularly in inflammatory or immune responses.\n", + "2. **Role in Pathways**: In the context of systems biology models that often study signaling and immune pathways, 'Ab_sR' may be involved in modulating signaling cascades. Since the documents mention the IL-6/sIL-6Rα complex, 'Ab_sR' might participate in pathways related to cytokine signaling, such as the interleukin-6 (IL-6) pathway, which is crucial in inflammation and immune regulation.\n", "\n", - "3. **Interactions with Other Molecules**: As the context heavily references IL-6, IL-6R, and associated signaling components like STAT3 and SOCS, it is plausible that 'Ab_sR' could interact with these molecules. It might bind to a receptor or signaling molecule to alter its activity.\n", + "3. **Interactions with Other Molecules**: Given the similarities to components like IL-6 and sIL-6Rα, 'Ab_sR' may interact with these molecules either as a part of a complex or influence their activity. For instance, antibodies or their fragments (like those potentially represented by 'Ab_sR') can bind to cytokines or their receptors, affecting the downstream signaling events.\n", "\n", - "4. **Importance in the Biological System**: Assuming 'Ab_sR' is an antibody related to receptor activity, it could be crucial in modulating inflammatory responses or other cytokine-related pathways. In systems biology models, such antibodies are often used to simulate therapeutic interventions, inhibiting specific pathways to predict changes in disease states or therapeutic outcomes.\n", + "4. **Importance in the Biological System Being Modeled**: Systems biology models often explore the dynamics and regulation of complex biochemical networks. If 'Ab_sR' is involved in cytokine-receptor interactions, it can be important in modulating inflammatory responses or immune system function, potentially making it a target for therapeutic interventions in diseases characterized by inflammation or immune dysfunction.\n", "\n", - "Without explicit details from the document, these inferences remain general and speculative. Further details would be needed for precise characterization.\n", + "To summarize, while 'Ab_sR' is not directly described in the context provided, it is likely associated with antibody or receptor functions within signaling or immune pathways similar to those of IL-6/sIL-6Rα in the documents referenced. If additional data is available, it could help refine or confirm these inferences.\n", "\n", "================================================================================\n", "27. Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw3667a5e1_02c9_44a0_acb4_b0431faa822d)\n", "================================================================================\n", - "Based on the context provided, there isn't directly available specific information about the species named 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, we can infer its role based on general knowledge and the content present in the documents.\n", + "The context provided does not offer any specific information about the species or molecule identified as 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' within the document. However, based on the excerpts, it is possible to infer the following general insights regarding similar biological components:\n", "\n", - "1. **Biological Function:** 'Ab' likely refers to an antibody, given the context of medical and pharmacological studies. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects, such as bacteria and viruses.\n", + "1. **Biological Function**: The molecule labeled 'Ab' is likely an antibody, which are proteins used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. In this context, 'Ab' might refer to an antibody targeting a particular biological pathway or molecule.\n", "\n", - "2. **Role in Pathways:** Antibodies are a crucial part of the immune response, often engaging in pathways related to immune regulation and inflammatory responses. Specifically, within the context, it seems to be involved in pathways targeting IL-6 or IL-6Rα, which are significant in inflammatory processes and immune system signaling, especially in conditions like inflammatory bowel diseases and other inflammatory responses.\n", + "2. **Role in Pathways**: Antibodies are typically involved in immune response pathways. The document mentions interactions that involve the cytokine IL-6 and its receptor, IL-6Rα. It is possible that 'Ab' could be an antibody aimed at either IL-6 or IL-6Rα, or their complex, to modulate immune responses.\n", "\n", - "3. **Interactions with Other Molecules:** Within the context, the antibodies interact with IL-6 and sIL-6Rα (soluble IL-6 receptor alpha). These interactions are essential as they form complexes that are targets for therapeutic interventions to suppress inflammatory markers like C-reactive protein (CRP). The effectiveness of such interventions can vary based on whether IL-6 and its receptor are targeted individually or together.\n", + "3. **Interactions with Other Molecules**: The document excerpt references the targeting of IL-6 or its receptor, sIL-6Rα. These molecules play roles in inflammatory processes, indicating that 'Ab' might interact with these molecules and potentially be used to suppress inflammation or other immune responses.\n", "\n", - "4. **Importance in the Biological System:** Antibodies, like the one inferred (potentially anti-IL-6 or similar), are important in modulating the immune response and are used in therapeutic settings to treat diseases where cytokine activity (like that of IL-6) is dysregulated. They help reduce undesirable inflammation and are thus a critical part of managing inflammatory diseases.\n", + "4. **Importance in the Biological System**: Antibodies like 'Ab' are important in a biological system because they can help to precisely modulate pathways that involve cytokines like IL-6, which are crucial in inflammatory and immune responses. This suggests its relevance in therapeutic interventions, especially in conditions where regulating immune activity is necessary.\n", "\n", - "In summary, while specific details about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' are not provided, it is most likely a therapeutic antibody involved in pathways targeting IL-6 and its receptor, pivotal in controlling inflammation within biological systems.\n", + "An understanding of similar antibodies, like anti-IL-6 or anti-IL-6R antibodies, typically helps in reducing inflammation and is useful in treating conditions like rheumatoid arthritis and other autoimmune diseases.\n", + "\n", + "In conclusion, while there is no direct information about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)', it can be inferred to be an antibody with potential functions related to immune modulation, likely within pathways involving IL-6 and its receptor(s).\n", "\n", "================================================================================\n", "28. Ab_R (ID: mw772cbf20_3fc1_4800_ae59_77884f1ae333)\n", "================================================================================\n", - "The document provided does not explicitly mention the species 'Ab_R' with the ID 'mw772cbf20_3fc1_4800_ae59_77884f1ae333.' Therefore, I will infer what 'Ab_R' might pertain to based on the general knowledge presented in the context and common biological components.\n", + "The context provided does not specifically mention the species 'Ab_R' with the ID mw772cbf20_3fc1_4800_ae59_77884f1ae333 located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e. However, the documents discuss the use of antibodies in modulating interleukin pathways, specifically targeting IL-6 and its receptor variants.\n", "\n", - "1. **Biological Function:**\n", - " - Given that the context mentions anti-IL-6 and anti-IL-6Rα antibodies, it is plausible that 'Ab_R' could represent an antibody (Ab) related to these immune system components. \n", + "Based on general knowledge and the context provided, Ab_R might represent an antibody related to the regulation or interaction with the IL-6 pathway or its receptors. \n", "\n", - "2. **Role in Pathways:**\n", - " - Antibodies targeting the IL-6/IL-6Rα pathway are involved in modulating inflammatory responses. IL-6 is a cytokine involved in immune regulation, and its receptor, IL-6Rα, can exist in both a soluble and membrane-bound form, playing roles in signaling cascades that promote inflammation.\n", + "1. **Biological Function**: If Ab_R is an antibody, its primary function might be to bind to specific targets, such as antigens or receptors like IL-6, sIL-6Rα, or the IL-6/IL-6R complex, to modulate immune responses or inflammatory pathways.\n", "\n", - "3. **Interactions with Other Molecules:**\n", - " - If 'Ab_R' is, in fact, an antibody similar to anti-IL-6 or anti-IL-6Rα, it would likely bind to these targets to inhibit cytokine signaling, thereby reducing inflammation. It may interact with IL-6, IL-6Rα, or both.\n", + "2. **Role in Pathways**: An antibody resembling Ab_R in this context could be involved in reducing inflammation by blocking the interaction between IL-6 and its receptor, preventing downstream signaling and overactivation of the immune response. This could be relevant in the context of diseases with inflammatory components.\n", "\n", - "4. **Importance in the Biological System Being Modeled:**\n", - " - The context of the document suggests a focus on modeling pharmacokinetics and pharmacodynamics (PK/PD) of antibodies targeting IL-6/IL-6Rα pathways, often to evaluate potential therapeutic interventions for conditions involving chronic inflammation, such as autoimmune diseases or inflammatory diseases like Crohn’s disease (CD).\n", - " - Such antibodies can serve as therapeutic agents to suppress the inflammatory response by antagonizing the IL-6 pathway, therefore reducing downstream effects like C-reactive protein (CRP) levels, which is a marker of inflammation.\n", + "3. **Interactions with Other Molecules**: Ab_R might interact with proteins like IL-6, its receptors, or complexes such as IL-6/IL-6R, aiming to modulate their activity or presence in the system, leading to changed concentrations of downstream inflammatory markers such as C-reactive protein (CRP).\n", + "\n", + "4. **Importance in the Biological System**: In the modeled biological system, such an antibody would be crucial for understanding and predicting therapeutic responses in diseases involving chronic inflammation, autoimmune conditions, or cancer. Its efficacious application could provide insights into novel therapeutic strategies.\n", "\n", - "Conclusively, while the document does not provide direct information on 'Ab_R,' it is likely aligned with therapeutic antibodies targeting cytokine signaling pathways to control inflammation within a modeled biological framework.\n", + "While specific information about 'Ab_R' is not available from the context, the inference aligns it with potentially important roles in immunological regulation through mechanisms of blocking or interacting with cytokine pathways, as seen in therapeutic antibodies targeting the IL-6 signaling axis.\n", "\n", "================================================================================\n", "29. Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) (ID: mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf)\n", "================================================================================\n", - "The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned in the provided context. However, it is possible to infer details about this species based on the context and general knowledge about similar biological components, such as sIL-6R and IL-6.\n", + "The provided context lacks specific information about the species identified as 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, based on general knowledge and the context concerning IL-6 and its soluble receptor sIL-6Rα, we can infer the following:\n", "\n", - "1. **Biological Function**: \n", - " - Since 'Ab_sR_IL6' likely refers to an antibody (Ab) targeting soluble IL-6 receptor (sIL-6R), its primary function would be to bind soluble IL-6R, potentially inhibiting its interaction with IL-6.\n", + "1. **Biological Function**: The molecule 'Ab_sR_IL6' likely functions as an antibody targeting the IL-6/sIL-6R complex. IL-6 is a cytokine involved in inflammatory and immune responses, and sIL-6R is its soluble receptor form. Antibodies targeting these molecules are typically designed to modulate the immune response, particularly in diseases characterized by excessive inflammatory signaling such as Crohn’s Disease.\n", "\n", - "2. **Role in Pathways**:\n", - " - In immune regulation pathways, particularly those involving interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R) can form complexes with IL-6 to mediate signaling even in cells that do not express membrane-bound IL-6R. By targeting sIL-6R, the antibody could disrupt these signaling cascades, serving as a potential therapeutic strategy in diseases characterized by excessive IL-6 signaling, such as rheumatoid arthritis or Crohn’s disease.\n", + "2. **Role in Pathways**: This antibody likely plays a role in blocking or modulating the pathway involving IL-6-mediated signaling. By binding to IL-6 and/or sIL-6R, it prevents their interaction with gp130, a co-receptor necessary for signal transduction, thereby inhibiting downstream signaling effects like the activation of STAT3 and the subsequent transcription of inflammatory genes.\n", "\n", - "3. **Interactions with Other Molecules**:\n", - " - Ab_sR_IL6 would primarily interact with sIL-6R, preventing it from binding to IL-6. This could impede the formation of the IL-6/sIL-6R complex, potentially reducing downstream signaling through the STAT3 pathway and other associated responses, such as C-reactive protein (CRP) production in the liver.\n", + "3. **Interactions with Other Molecules**: The primary interaction of 'Ab_sR_IL6' would be with IL-6 and sIL-6Rα, limiting their availability to participate in inflammatory signaling. This kind of interaction is often employed to reduce levels of inflammatory mediators like C-reactive protein (CRP) in the circulation.\n", "\n", - "4. **Importance in the Biological System Being Modeled**:\n", - " - In the context of a model focused on immune regulation, particularly in conditions like Crohn’s disease, targeting sIL-6R with an antibody could be critical in modulating the inflammatory response. By acting on the IL-6 signaling pathway, such an approach could help manage systemic inflammation and related symptoms.\n", + "4. **Importance in the Biological System**: In the context of the document, which seems to be related to inflammatory diseases such as Crohn's Disease, the importance of 'Ab_sR_IL6' would be in its potential therapeutic application. By reducing IL-6 signaling, it could help in controlling inflammation and alleviating disease symptoms.\n", "\n", - "While there is no specific mention of 'Ab_sR_IL6' in the provided documents, understanding its potential role can be inferred based on known dynamics of IL-6, sIL-6R, and their involvement in immune and inflammatory processes.\n", + "In summary, while specific details about 'Ab_sR_IL6' are not provided, its naming and context imply it is an antibody targeting key components of the IL-6 signaling pathway with potential significance in therapeutic interventions for inflammatory conditions.\n", "\n", "================================================================================\n", "30. sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mw7becb5fe_8da8_4285_a821_0d77ad811b62)\n", "================================================================================\n", - "Based on the provided context, there is no specific mention or detailed description of a species or molecule named 'sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, we can infer information about its potential biological role based on general knowledge of similar components in the context of the document, which discusses IL-6 signaling pathways.\n", + "The species 'sR_IL6' (ID: mw7becb5fe_8da8_4285_a821_0d77ad811b62) located in 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5' likely refers to a soluble receptor component involved in IL-6 signaling pathways. Although the provided context does not give explicit details about 'sR_IL6', we can infer its role based on the mention of 'sIL-6R' and related IL-6 signaling pathways:\n", + "\n", + "1. **Biological Function**: 'sR_IL6' is likely a soluble form of the IL-6 receptor, similar to 'sIL-6R'. Soluble receptors often serve to modulate cytokine signaling, either by extending the half-life of the cytokine in circulation, facilitating its transport, or altering its activity. \n", + "\n", + "2. **Role in Pathways**: The context suggests that IL-6 signals through both classical and trans-signaling pathways. In the context of immune regulation and Crohn's disease, the IL-6/sIL-6Rα complex is involved in the modulation of inflammatory responses. 'sR_IL6' is expected to participate in these pathways, potentially influencing the interaction with sgp130, a natural inhibitor of the trans-signaling route.\n", "\n", - "The document prominently features IL-6 (Interleukin-6) and its role in the context of immune regulation, particularly in relation to Crohn’s disease. IL-6 is a cytokine involved in inflammation and immune responses. It signals through two main pathways: classical signaling and trans-signaling. In classical signaling, IL-6 binds to its membrane-bound receptor, IL-6R, and subsequently recruits gp130, leading to the activation of downstream pathways such as the JAK/STAT pathway. In trans-signaling, IL-6 can also bind to a soluble form of its receptor, sIL-6R, allowing it to act on cells that do not express membrane-bound IL-6R.\n", + "3. **Interactions with Other Molecules**: 'sR_IL6' would interact with IL-6, forming complexes that could be sequestered by sgp130, as well as interact with factors involved in immune signaling, such as STAT3, CRP, and possibly others involved in downstream signaling and gene transcription related to immune modulation.\n", "\n", - "Given the emphasis on IL-6 and sIL-6R in the context, 'sR_IL6' could refer to a soluble receptor or a related soluble component in the IL-6 signaling pathway. This type of molecule typically facilitates trans-signaling interactions. It may interact with IL-6 to form a complex that can then engage with another component, sgp130, to modulate signaling. This complex plays a role in regulating immune responses and could have therapeutic implications, especially in diseases like Crohn’s disease where IL-6 signaling is dysregulated.\n", + "4. **Importance in the Biological System**: The role of such soluble receptors is crucial in modulating the availability and activity of cytokines like IL-6. They can influence the strength and duration of signaling in different compartments, vital for maintaining balance in immune responses, particularly in diseases like Crohn's where cytokine signaling can be dysregulated.\n", "\n", - "In summary, if 'sR_IL6' is indeed related to IL-6 signaling, its biological importance might lie in modulating inflammatory responses through trans-signaling, interacting with IL-6 and possibly other soluble receptors or signaling molecules in this pathway. Its role would be crucial in maintaining homeostasis in immune function and could be a target for therapeutic interventions.\n", + "Based on this inference, 'sR_IL6' appears to be an important modulator within the IL-6 signaling network potentially involved in regulatory mechanisms relevant to inflammation and immune response in the context of Crohn’s disease.\n", "\n", "================================================================================\n", "31. gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca)\n", "================================================================================\n", - "Based on the provided context, here is the summarized background information about the gp130 species:\n", + "Based on the provided context, the species 'gp130' is involved in the interleukin-6 (IL-6) signaling pathway. Gp130 plays a crucial role as a signal transducer for the IL-6 family of cytokines. It forms a complex with the IL-6/IL-6 receptor (IL-6R) to propagate intracellular signaling leading to various biological responses.\n", "\n", - "1. **Biological Function**: gp130 is a protein that plays a critical role in signaling pathways, specifically as part of the interleukin-6 (IL-6) signaling pathway. It acts as a key signal transducer and is involved in the formation of a signaling complex with the IL-6 receptor.\n", + "1. **Biological Function**: Gp130 is involved in mediating the effects of cytokines, particularly IL-6. It is a part of the receptor complex that includes the IL-6 receptor and gp130. When IL-6 binds to its receptor, gp130 is recruited to form a signaling complex, which then initiates downstream signaling pathways such as JAK/STAT, MAPK, and PI3K/Akt.\n", "\n", - "2. **Role in Pathways**: gp130 is an integral component of the signaling complex formed between IL-6 and its soluble receptor, sIL-6Rα. The complex formation is crucial for IL-6 trans-signaling, which is implicated in various inflammatory responses.\n", + "2. **Role in Pathways**: Gp130 is central to the IL-6 signaling pathway, which is involved in immune responses, inflammation, and cell survival. It is indispensable for the transmission of signals that lead to the activation of transcription factors such as STAT3, which can then affect the expression of various genes involved in inflammatory responses.\n", "\n", - "3. **Interactions with Other Molecules**: gp130 interacts with IL-6 and sIL-6Rα to form a hexameric complex that is necessary for initiating the downstream signaling cascade. Soluble gp130 (sgp130) acts as a natural inhibitor by binding to this complex, thereby preventing trans-signaling.\n", + "3. **Interactions with Other Molecules**: Gp130 interacts specifically with the IL-6/IL-6R complex to transmit cytokine-mediated signals. Additionally, soluble forms of gp130 (sgp130) act as natural inhibitors of IL-6 signaling by binding to IL-6/soluble IL-6R complexes, thereby preventing them from interacting with membrane-bound gp130.\n", "\n", - "4. **Importance in the Biological System**: In the context of the system being modeled, soluble gp130 (sgp130) is considered a potential therapeutic agent, especially in conditions like Crohn's disease, due to its ability to inhibit IL-6 trans-signaling. However, the effectiveness of sgp130 is dependent on achieving high and frequent doses, as small alterations in sgp130 levels have minimal impact due to its high baseline concentration relative to IL-6.\n", + "4. **Importance in the Biological System**: In the context of inflammatory diseases such as Crohn's disease, modulation of gp130 and its associated signaling pathways represents a potential therapeutic strategy. Soluble gp130 (sgp130Fc), a fusion protein combining the extracellular portion of gp130 with an Fc region, has been studied for its ability to inhibit IL-6 trans-signaling, highlighting its therapeutic potential in conditions characterized by excessive or dysregulated IL-6 activity.\n", "\n", - "Overall, gp130 is pivotal for IL-6-mediated signaling, and modifications in its activity can potentially modulate inflammatory pathways, making it a significant target in certain therapeutic approaches.\n", + "Overall, gp130 is a critical component of the IL-6 signaling pathway, with its function as both a necessary signal transducer and a target for therapeutic inhibition in inflammatory diseases.\n", "\n", "================================================================================\n", "32. R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9)\n", "================================================================================\n", - "Based on the context provided, the species named 'R_IL6_gp130' appears to relate to the interleukin-6 (IL-6) signaling pathway, which involves the interaction of IL-6 with its receptor components for signal transduction. Although specific details about this species are not directly provided in the context, we can infer its characteristics and role based on the general knowledge of similar biological components involved in IL-6 signaling:\n", + "Based on the context and information provided, the specifics about the species named 'R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' are not directly detailed. However, by piecing together related information and general knowledge, we can infer some aspects of its characteristics and role in biological systems:\n", "\n", - "1. **Biological Function**: R_IL6_gp130 likely represents a complex involving IL-6, its specific receptor, and the signal transducer gp130. In the IL-6 signaling pathway, gp130 serves as a critical signal transducer that, upon activation by the IL-6/IL-6 receptor complex, initiates intracellular signaling cascades that influence gene expression.\n", + "1. **Biological Function**: 'R_IL6_gp130' likely represents the interaction or complex involving the interleukin-6 (IL-6) signaling pathway and the gp130 co-receptor. IL-6 is a cytokine involved in immune responses, inflammation, and hematopoiesis. Gp130 is a signal transducer for cytokines in the IL-6 family and plays a crucial role in transmitting signals from cytokine receptors.\n", "\n", - "2. **Role in Pathways**: This species is part of the IL-6 signaling pathway, which can activate the JAK/STAT signaling cascade, resulting in the phosphorylation of STAT3 (Signal Transducer and Activator of Transcription 3). This pathway is crucial in mediating inflammatory responses and plays a role in various physiological and pathological processes, including immune regulation, inflammation, and cell growth.\n", + "2. **Role in Pathways**: The IL-6/gp130 complex is essential in the IL-6 signaling pathway, which influences various biological processes including inflammation, immune response, and acute phase reactions. This pathway can operate through classical signaling using membrane-bound receptors or trans-signaling with soluble receptors and receptors like gp130.\n", "\n", - "3. **Interactions with Other Molecules**: R_IL6_gp130 likely interacts with IL-6 and its soluble receptor (sIL-6R), as well as with gp130. This interaction forms a complex that facilitates signal transduction through the gp130 component, leading to downstream effects such as the activation of STAT3. It can also interact with inhibitors like soluble gp130 (sgp130) or fusion proteins designed to modulate this signaling pathway.\n", + "3. **Interactions with Other Molecules**: The IL-6 signaling pathway involves interactions between IL-6, soluble IL-6 receptor (sIL-6R), and gp130. It is noted that soluble gp130 (sgp130) can inhibit IL-6 trans-signaling, which suggests that 'R_IL6_gp130' might be relevant in modulating or forming complexes crucial for either inhibiting or promoting the IL-6 signal.\n", "\n", - "4. **Importance in the Biological System**: Within the context described, R_IL6_gp130 is important for understanding the dynamics of IL-6 signaling, especially in inflammatory conditions such as Crohn's disease. The IL-6 pathway is targeted for therapeutic intervention, suggesting its significance in disease pathology and treatment.\n", + "4. **Importance in Biological System**: In the context of the system being modeled (likely involving conditions like Crohn's disease), targeting the IL-6/gp130 pathway may have therapeutic implications. Efforts such as using sgp130Fc fusion proteins to inhibit IL-6 trans-signaling highlight the importance of understanding and manipulating this complex in disease models for potential treatment strategies.\n", "\n", - "In summary, R_IL6_gp130 likely represents a key component of the IL-6 signaling pathway, central to mediating the effects of IL-6 through gp130 in inflammation and immune response, as inferred from the general function of similar complexes.\n", + "Therefore, 'R_IL6_gp130' in this context probably signifies a key component or step within the IL-6 signaling pathway, with potential roles in modulating inflammatory responses, significant to modeling diseases like Crohn's disease.\n", "\n", "================================================================================\n", "33. Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw6cce2109_0e32_4dd9_98ec_41173e8ef07d)\n", "================================================================================\n", - "Based on the provided context, there appears to be no specific information about the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' within the text. However, the context discusses the IL-6 signaling pathway and its components, particularly focusing on the interactions between IL-6, sIL-6Rα, and therapeutic antibodies, such as the humanized anti-interleukin 6 receptor antibody (tocilizumab). This suggests a theme centered around immune response regulation, specifically in diseases like rheumatoid arthritis and possibly Crohn's disease.\n", + "The provided context does not directly reference the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' or its ID: mw6cce2109_0e32_4dd9_98ec_41173e8ef07d. However, we can attempt to infer its possible characteristics and role based on the general information available in the context, which focuses on IL-6-mediated immune regulation in Crohn's Disease, using a multiscale model.\n", "\n", - "In the absence of specific information about 'Ractive', we can infer its potential role based on the discussed biological components. It is likely that 'Ractive' could be involved in the pathways related to cytokine signaling, immune modulation, or therapeutic interactions similar to those of IL-6 or its receptor complex. Its importance in the system may be linked to modulating immune responses or serving as a target or mediator in therapeutic approaches within the context of the mentioned diseases.\n", + "1. **Biological Function:**\n", + " The document is centered around the regulation of IL-6, interleukin-6, which is an important cytokine involved in inflammatory and immune responses. While Ractive itself is not mentioned, it could potentially be related to or a component interacting within the IL-6 signaling pathways.\n", + "\n", + "2. **Role in Pathways:**\n", + " Since the context enlightens the importance of the IL-6/sIL-6Rα complex in IL-6 signaling, Ractive might play a role in a related or auxiliary pathway, possibly as a regulatory or signaling molecule.\n", + "\n", + "3. **Interactions with Other Molecules:**\n", + " The IL-6 signaling pathway involves interactions between IL-6, IL-6 receptors, sIL-6Rα (soluble IL-6 receptor), and antibodies like tocilizumab (anti-IL-6Rα). It's plausible that Ractive could interact with similar molecules or influence the pathway indirectly.\n", + "\n", + "4. **Importance in the Biological System:**\n", + " Given the context's focus on immune regulation and Crohn's Disease, Ractive could be assumed as an important component in the signaling or regulatory mechanisms within this biological model, potentially influencing cytokine behavior, immune response modulation, or drug interactions.\n", "\n", - "In systems biology modeling, species or molecules like 'Ractive' could be critical for either transmitting signals within a pathway, modifying the activity of other molecules, or acting as a checkpoint or target for drugs designed to alter biological responses in conditions like Crohn's disease or rheumatoid arthritis.\n", + "In summary, while there's no specific information on Ractive, its inferred role might be associated with IL-6 signaling, immune pathway interactions, or drug (such as antibody) responses within the described model of immune regulation.\n", "\n", "================================================================================\n", "34. STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw2b255f94_8018_4b99_bde8_918eeac45446)\n", "================================================================================\n", - "Based on the provided context, the species 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is likely referring to the well-known protein STAT3, a signal transducer and activator of transcription 3. Here is the relevant background information about STAT3:\n", + "Based on the available context from the provided documents, STAT3 appears to refer to \"signal transducer and activator of transcription 3\". This molecule is a critical component in the JAK/STAT signaling pathway, which is involved in transducing extracellular signals into cellular responses. The context mentions that phosphorylation of STAT3 is important, suggesting that it becomes activated through the addition of a phosphate group. Activated or phosphorylated STAT3 (pSTAT3) can then translocate to the nucleus where it functions as a transcription factor regulating the expression of various genes.\n", "\n", - "1. **Biological Function**:\n", - " - STAT3 is involved in the phosphorylation process as part of cell signaling. Phosphorylated STAT3 (pSTAT3) is indicative of its active state, which can translocate to the nucleus to act as a transcription factor.\n", - " - It plays a crucial role in relaying signals from cytokine receptors, like the IL-6 receptor complex, to the nucleus, influencing gene expression.\n", + "**Biological Function:**\n", + "STAT3 plays a key role in mediating the effects of various cytokines and growth factors by regulating gene expression. It is involved in controlling multiple cellular processes such as cell growth, apoptosis, and differentiation.\n", "\n", - "2. **Role in Pathways**:\n", - " - STAT3 is a central component of the JAK-STAT signaling pathway. Once activated, it typically mediates the effects of cytokines, such as IL-6, contributing to various cellular responses, including growth, differentiation, and survival.\n", - " - The context mentions its involvement in pathways activated by IL-6, a cytokine that triggers immune responses, inflammation, and acute-phase reactions.\n", + "**Role in Pathways:**\n", + "STAT3 is a central player in the JAK/STAT signaling pathway. It is specifically mentioned in the context of IL-6 signaling, where it is activated downstream of interleukin-6 receptor engagement, which can involve both classical and trans-signaling mechanisms.\n", "\n", - "3. **Interactions with Other Molecules**:\n", - " - STAT3 gets activated by cytokines binding to their respective receptors, leading to JAK kinases' activation, which subsequently phosphorylates STAT3.\n", - " - It interacts with components of the IL-6 receptor family, specifically affecting the pathways involving IL-6 trans-signaling.\n", - " - The context also suggests interactions involving sIL-6R (a soluble IL-6 receptor) and sgp130 (a soluble form of the co-receptor gp130), where pSTAT3 acts in various compartments like the GI tract and liver depending on cytokine signaling.\n", + "**Interactions with Other Molecules:**\n", + "STAT3 interacts with IL-6 and its receptors (such as sIL-6R and gp130), and phosphorylation of STAT3 can be triggered by cytokines binding to these receptors. The document implies interactions with components like C-reactive protein (CRP) and possibly engagements involving soluble forms of receptors like sgp130, which can modulate signaling.\n", "\n", - "4. **Importance in the Biological System**:\n", - " - STAT3 is important in modeling biological systems that involve immune responses or inflammation, such as in the context of Crohn's disease, as indicated by increased pSTAT3 levels in serum and tissues affected by the disease.\n", - " - Its role as a transcription factor makes it key in regulating downstream gene expression that could contribute to disease pathology and the body's response to inflammation.\n", + "**Importance in the Biological System Being Modeled:**\n", + "STAT3's significance in the biological model investigated (likely related to inflammatory diseases like Crohn’s disease) lies in its role in mediating cytokine signaling that could lead to inflammation and other immune responses. The upregulation of phosphorylated STAT3 in specific tissue biopsies, such as those from the colon in Crohn’s disease, suggests its involvement in inflammatory pathogenic mechanisms.\n", "\n", - "In summary, although there is no direct mention of a species specifically labeled 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' in the document, the general characteristics and functions of STAT3 can be inferred based on common scientific knowledge and the provided context about IL-6 signaling and related pathways.\n", + "Overall, STAT3 is a crucial component in understanding how intracellular pathways translate external signals into gene expression changes that affect biological outcomes and diseases.\n", "\n", "================================================================================\n", "35. pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2) (ID: mw48867e93_f170_44e8_ac7a_185b23e1bf3b)\n", "================================================================================\n", - "Based on the context provided, specific information about the biological species 'pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is not explicitly detailed. However, we can infer its role and significance based on the general knowledge about pSTAT3 and its involvement in biological processes.\n", + "The provided context does not contain detailed or specific information about the species pSTAT3 identified by the ID mw48867e93_f170_44e8_ac7a_185b23e1bf3b, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. Therefore, I will provide a summary based on general knowledge about pSTAT3 and its role in biological systems.\n", "\n", - "1. **Biological Function:**\n", - " - pSTAT3, or phosphorylated STAT3, is a form of Signal Transducer and Activator of Transcription 3 (STAT3) that becomes activated through phosphorylation. This activation enables pSTAT3 to translocate to the cell nucleus, where it functions as a transcription factor, promoting the expression of various genes involved in cell growth, survival, and differentiation.\n", + "**Background Information on pSTAT3:**\n", "\n", - "2. **Role in Pathways:**\n", - " - In the context described, pSTAT3 is associated with IL-6 signaling, which involves classical and trans-signaling pathways. IL-6 is a cytokine involved in immune response, and its interaction with receptors such as IL-6R and gp130 leads to the activation of JAK kinases and subsequent phosphorylation of STAT3 (pSTAT3). This signaling cascade is crucial in mediating responses to inflammation and stress.\n", + "- **Biological Function:**\n", + " pSTAT3 refers to the phosphorylated form of the STAT3 protein, which stands for Signal Transducer and Activator of Transcription 3. STAT3 is a transcription factor that, when phosphorylated, becomes activated and dimerizes. This activated dimer can then translocate to the nucleus to modulate the expression of specific target genes.\n", "\n", - "3. **Interactions with Other Molecules:**\n", - " - pSTAT3 interacts with the IL-6 receptor complex, including sIL-6R (soluble IL-6 receptor) and sgp130 (soluble gp130). The complex formation and subsequent signaling facilitate various downstream effects. pSTAT3 is known to regulate the expression of suppressor of cytokine signaling (SOCS) proteins and other gene products involved in modulating immune responses.\n", + "- **Role in Pathways:**\n", + " STAT3 is primarily involved in the JAK-STAT signaling pathway. Upon activation, typically through cytokine signaling such as IL-6, STAT3 is phosphorylated by Janus kinases (JAKs). pSTAT3 plays a crucial role in mediating responses to extracellular signaling and is involved in various biological processes such as cell growth, differentiation, and survival.\n", "\n", - "4. **Importance in the Biological System Being Modeled:**\n", - " - pSTAT3 plays a critical role in inflammatory responses, as highlighted by its reported increase in serum concentrations in conditions like Crohn’s disease. It is involved in the transcriptional regulation of acute-phase proteins such as C-reactive protein (CRP) and other gene products that are significant in the immune response and inflammation within the gastrointestinal tract and liver.\n", + "- **Interactions with Other Molecules:**\n", + " pSTAT3 interacts with JAKs as part of its activation. It is also involved in crosstalk with other signaling molecules and pathways, including IL-6, sIL-6R (soluble IL-6 receptor), and gp130. These interactions facilitate a range of cellular responses, including modulation of immune response, inflammation, and cellular proliferation.\n", + "\n", + "- **Importance in the Biological System:**\n", + " pSTAT3 is an important mediator in immune responses and inflammation. It has been implicated in various diseases, including inflammatory bowel diseases like Crohn's disease, where increased levels of pSTAT3 have been observed in affected tissues. It also plays a role in cancer progression, where aberrant STAT3 activity contributes to tumorigenesis.\n", "\n", - "This inferred information helps underscore the importance of pSTAT3 in immune modulation and its potential implications in inflammatory diseases, even though specific details about its ID-specific characteristics in the context were not provided.\n", + "In the context of the document, mention of pSTAT3 suggests its potential involvement in IL-6 signaling pathways, possibly related to immune and inflammatory responses as well as transcriptional regulation of genes relevant to the conditions being discussed (e.g., Crohn’s disease or similar inflammatory conditions).\n", "\n", "================================================================================\n", "36. geneProduct (ID: mw0083d743_836f_4238_a17f_4602193d5bc0)\n", "================================================================================\n", - "The provided context from the document does not include specific details about the biological species or molecule identified as 'geneProduct' with the ID: mw0083d743_836f_4238_a17f_4602193d5bc0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. There is no explicit mention of this molecule's biological function, role in pathways, interactions with other molecules, or its importance in the biological system being modeled.\n", + "The provided context does not specifically describe the species named 'geneProduct' with the ID 'mw0083d743_836f_4238_a17f_4602193d5bc0' located in 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5'. However, based on the general context and common knowledge within systems biology, we can infer some plausible information about 'geneProduct' in relation to similar biological components:\n", "\n", - "Based on the context, which predominantly discusses interleukin-6 (IL-6) pathways, receptors, and related molecules (e.g., sIL-6R, gp130, and sgp130), we can infer that 'geneProduct' might be related to the IL-6 signaling pathway or another signaling molecule involved in inflammatory or immune responses. In systems biologically concerned with inflammation or cytokine signaling, such gene products might typically be involved in cell signaling cascades, playing roles in activating transcription factors, interacting with receptors or co-receptors, and affecting the expression of downstream genes important for cellular responses.\n", + "1. **Biological Function**: Given that 'geneProduct' is mentioned in the context of IL-6 signaling and STAT3 activation, it could be a gene product related to cytokine signaling pathways. Gene products involved in this pathway typically play roles in immune responses, inflammation, cell survival, and proliferation.\n", "\n", - "Since specific data is not available, hypothetical pathways could involve roles similar to those of IL-6 or its receptors—modulating inflammatory responses, and participating in acute phase reactions, including CRP production in the liver. Gene products in such pathways often interact with other cytokines, receptors, and intracellular signaling proteins to exert their effects, potentially influencing processes like cell proliferation, differentiation, and survival.\n", + "2. **Role in Pathways**: The context includes references to IL-6, sIL-6R, and associated signaling pathways, such as those involving STAT3 and SOCS. 'geneProduct' may be involved in modulating these pathways, possibly influencing downstream effects such as gene transcription.\n", "\n", - "================================================================================\n", - "37. sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mwd31f52cc_04e7_40e0_885f_c7b2d9e62215)\n", - "================================================================================\n", - "Based on the context provided, there is no explicit mention of the species 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' directly in the excerpts. However, we can infer some related information using general knowledge and by examining the related components and interactions in the context shared.\n", + "3. **Interactions with Other Molecules**: 'geneProduct' might interact with key proteins and receptors in the IL-6 signaling pathway, such as IL-6, sIL-6R, gp130, and sgp130. These interactions could be crucial for the regulation and fine-tuning of the signaling pathway.\n", "\n", - "The context revolves around the interaction and dynamics involving the Interleukin-6 (IL-6) signaling pathway, soluble IL-6 receptor (sIL-6R), and the involvement of other molecules like sgp130. \n", + "4. **Importance in the Biological System**: If 'geneProduct' participates in IL-6 signaling, it could be important for processes like acute phase responses, immune regulation, and potentially in the context of diseases where IL-6 plays a role, such as autoimmune disorders or chronic inflammatory conditions.\n", "\n", - "### Inferred Background Information about 'sR':\n", + "Without specific information, these inferences are speculative but based on common roles and interactions seen within such pathways.\n", "\n", - "1. **Biological Function:**\n", - " - In the context of cytokine signaling, receptors like sR are generally involved in recognizing and binding to specific signaling molecules (e.g., cytokines such as IL-6) to facilitate their biological functions. Therefore, 'sR' could act as a receptor or part of a receptor complex in signaling pathways.\n", + "================================================================================\n", + "37. sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mwd31f52cc_04e7_40e0_885f_c7b2d9e62215)\n", + "================================================================================\n", + "Based on the provided context, there is specific mention of an interaction between sR and IL-6. Although the document does not explicitly describe the species labeled as 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)', we can infer its potential role and importance by drawing parallels to similar entities mentioned in the system's model involving IL-6 signaling.\n", "\n", - "2. **Role in Pathways:**\n", - " - Given the presence of IL-6 and its receptor dynamics (e.g., IL-6/sIL-6R complex) in the context, 'sR' might participate in cytokine signaling pathways, potentially serving as a modulator that enhances or inhibits signal transduction depending on its specific interactions with IL-6 or other pathway components like sgp130.\n", + "### Inferred Information about sR:\n", "\n", - "3. **Interactions with Other Molecules:**\n", - " - The sIL-6R forms complexes with IL-6, which then interact with membrane-bound receptors to initiate signaling cascades like the activation of STAT3. 'sR' might potentially interact similarly, indicating a critical role in modifying the intensity or outcome of the signaling process.\n", + "- **Biological Function**: \n", + " - The 'sR' is likely a soluble receptor or receptor component involved in the IL-6 signaling pathway, given its contextual relationship with IL-6 and similar naming conventions to 'sIL-6R' and its complex with IL-6 ('IL-6:sR').\n", "\n", - "4. **Importance in the Biological System Being Modeled:**\n", - " - The balance of soluble receptors and cytokines (such as IL-6/sIL-6R) and their interactions with other molecules (e.g., sgp130) are essential for controlling inflammatory responses and other downstream effects (e.g., CRP production in the liver).\n", - " - Given this, 'sR' could play a pivotal regulatory role, affecting the system's sensitivity to changes in cytokine levels and potentially serving as a target for therapeutic interventions.\n", + "- **Role in Pathways**:\n", + " - It seems to participate in modulating IL-6 activity. The mention of 'IL-6:sR' implies that the sR might form complexes with IL-6, influencing the signaling dynamics, possibly acting as a decoy receptor or as a mediator that facilitates or modifies downstream signaling.\n", + " \n", + "- **Interactions with Other Molecules**:\n", + " - The document discusses complexes such as 'IL-6:sR' and 'IL-6:sR:sgp130'. This suggests that sR interacts directly with IL-6 and possibly with other soluble components like sgp130, which is known to modulate IL-6 trans-signaling.\n", "\n", - "### Conclusion:\n", + "- **Importance in the Biological System**:\n", + " - While sR's specific function was not detailed, its involvement in forming complexes such as 'IL-6:sR' suggests a regulatory role in the IL-6 pathway, which is crucial for inflammatory and immune responses.\n", + " - The interaction between sR and IL-6 may have implications for therapeutic targets, particularly in conditions where IL-6 signaling is dysregulated.\n", "\n", - "While the provided document excerpts do not explicitly detail 'sR's identity or function, its inferred associations with key players like IL-6, sIL-6R, and sgp130 suggest a role in cytokine signaling modulation, particularly in pathways relevant to inflammation and immune response. For specific molecular functions and pathway roles, further examination of full-length documents or additional sources would be required.\n", + "In summary, 'sR' likely plays a critical part in the IL-6 signaling pathway, influencing the biological effects of IL-6 through complex formation and interaction with other soluble proteins like sgp130. Understanding its role would be important for modeling systemic inflammatory responses and potentially informs therapeutic strategies targeting IL-6 pathways.\n", "\n", "================================================================================\n", "38. IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mw2c9b0499_3325_4394_8af3_bbf653a944a0)\n", "================================================================================\n", - "Based on the provided context and general knowledge, the species named 'IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' is likely referring to Interleukin-6 (IL-6), a cytokine involved in various biological functions and pathways. Here is a summary of its roles and significance:\n", + "Based on the provided context, IL-6 (likely referring to the cytokine Interleukin-6) is a significant player in the immune regulation associated with Crohn’s disease. Here is a summary of the relevant information extracted about IL-6:\n", "\n", - "1. **Biological Function:**\n", - " - IL-6 is a multifunctional cytokine that plays a critical role in immune response regulation, inflammation, and hematopoiesis.\n", - " - It is known to be a mediator of fever and of the acute phase response.\n", + "1. **Biological Function**: IL-6 is a cytokine that plays a critical role in immune responses. It is involved in the survival of T-cells and contributes to their apoptosis resistance, especially in the lamina propria, a tissue layer in the intestines. This function is particularly relevant in the context of inflammatory diseases such as Crohn's disease.\n", "\n", - "2. **Role in Pathways:**\n", - " - IL-6 signaling occurs via two main pathways: the classical signaling pathway and the trans-signaling pathway.\n", - " - The classical pathway involves IL-6 binding to a membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of IL-6Rα (sIL-6Rα).\n", - " - Both pathways converge on a signal transduction cascade that activates Janus kinase (Jak) proteins and leads to the phosphorylation of signal transducer and activator of transcription 3 (STAT3).\n", + "2. **Role in Pathways**: IL-6 signaling can occur through two main pathways:\n", + " - The **classical pathway**, mediated by a membrane-bound IL-6 receptor (IL-6Rα).\n", + " - The **trans-signaling pathway**, mediated by a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor to form an active complex that leads to downstream signaling events, including the phosphorylation of Janus kinase (Jak) family proteins and the activation of signal transducer and activator of transcription 3 (STAT3).\n", "\n", - "3. **Interactions with Other Molecules:**\n", - " - IL-6 interacts with its receptor IL-6Rα (either membrane-bound or soluble) and forms a complex that recruits the gp130 coreceptor.\n", - " - This interaction is crucial for activating downstream signaling pathways that are involved in immune responses.\n", + "3. **Interactions with Other Molecules**: IL-6 interacts with its receptor IL-6Rα (both in its membrane-bound and soluble forms) to initiate signaling. In the classical signaling pathway, the IL-6/IL-6Rα complex recruits gp130 to form a functional receptor complex. This interaction initiates a cascade, leading to the activation of downstream signaling molecules, including Jak and STAT3.\n", "\n", - "4. **Importance in the Biological System:**\n", - " - IL-6 is particularly important in inflammatory diseases such as Crohn's disease, where it contributes to enhanced T-cell survival and resistance to apoptosis in the intestinal mucosa, as well as elevated chemokine secretion.\n", - " - It plays a significant role in the pathophysiology of autoimmune diseases and chronic inflammatory conditions, making it a target for therapeutic interventions such as with specific antibodies like tocilizumab.\n", + "4. **Importance in the Biological System**: IL-6 is crucial in the modulation of immune responses, which are essential in the context of inflammatory diseases like Crohn’s disease. It enhances the survival of T-cells, contributing to the chronic inflammation characteristic of this condition. The trans-signaling pathway, involving the soluble IL-6Rα, is particularly noted for its importance in disease, highlighting IL-6's role in promoting inflammatory pathways.\n", "\n", - "In summary, IL-6 is a central cytokine in immune regulation and inflammatory processes, which makes it a pivotal part of the biological system being modeled, particularly in the context of diseases like Crohn's disease.\n", + "Overall, IL-6 is depicted as a pivotal cytokine in driving the immune responses that characterize inflammatory diseases, and its pathways and interactions are potential targets for therapeutic intervention.\n", "\n", "================================================================================\n", "39. sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mwd65b5b39_dc1b_4e77_a999_67277a880e5e)\n", "================================================================================\n", - "Based on the provided context, here is the background information about the species 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)':\n", + "The species or molecule 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' seems to be referring to a soluble form of gp130, which is a component of the IL-6 signaling pathway. Here is a summary of the relevant background information based on the provided excerpts:\n", "\n", - "### Biological Function:\n", - "sgp130, known here as a species variant, reflects a biological molecule related to the inhibition of IL-6 trans-signaling. It specifically refers to a fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is designed to inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex.\n", + "1. **Biological Function**:\n", + " - sgp130 functions as an inhibitor of IL-6 trans-signaling, which is a process involving the IL-6 signaling pathway. This occurs when sgp130 binds to the IL-6/sIL-6Rα complex, effectively blocking its ability to signal.\n", "\n", - "### Role in Pathways:\n", - "sgp130 plays a role in pathways involving the interleukin-6 (IL-6) signaling cascade. It specifically targets the IL-6/sIL-6Rα complex, blocking the trans-signaling pathway that can contribute to inflammatory responses, such as those observed in Crohn’s disease.\n", + "2. **Role in Pathways**:\n", + " - sgp130 is involved in the IL-6 signaling pathway, particularly in the inhibition of IL-6 trans-signaling. This pathway is significant in inflammation and immune response, and it involves interactions with the soluble IL-6 receptor (sIL-6Rα).\n", "\n", - "### Interactions with Other Molecules:\n", - "sgp130 interacts with the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc binds this complex with the same affinity as natural sgp130, thus inhibiting the signaling pathways mediated by IL-6.\n", + "3. **Interactions with Other Molecules**:\n", + " - sgp130 interacts with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 prevents IL-6 from engaging with membrane-bound gp130, thus inhibiting downstream signaling events.\n", "\n", - "### Importance in the Biological System:\n", - "sgp130 appears to be of limited effect in altering the steady-state values of certain biomarkers unless present in large quantities. It exists in excess compared to free IL-6, leading to minimal effect from small perturbations in its levels. Hence, any significant observable effects require substantial changes in sgp130 concentrations.\n", + "4. **Importance in the Biological System Being Modeled**:\n", + " - In the modeling context provided, altering the levels of sgp130 has minimal effect on the system due to its high baseline levels compared to the much lower concentrations of free IL-6. This suggests that while sgp130 is present in excess, significant changes in its levels are required to observe an impact on system outputs.\n", + " - The effectiveness of sgp130-based therapies appears limited under normal conditions and requires high doses for observable effects, particularly in the suppression of CRP (C-reactive protein) levels and pSTAT3 in the gut.\n", + " - The sensitivity analysis of the system model indicates that sgp130 is among the least influential parameters for output biomarkers, suggesting that targeting IL-6 and its receptor may be more effective for therapeutic interventions.\n", "\n", - "Despite its biological function, the context suggests that sgp130-based therapeutic strategies may not be as robust as anticipated. The sensitivity analysis indicated that the output biomarkers are less affected by sgp130 levels, making IL-6 and sIL-6Rα more potent targets for intervention in the studied system. This contributes to understanding its therapeutic potential limitations, particularly in addressing diseases like Crohn's where IL-6 signaling is implicated.\n", + "Overall, sgp130 plays a regulatory role in the IL-6 signaling pathway by acting as a natural inhibitor, but in the context of the model discussed, its predominant presence makes it less impactful for modifying system dynamics without high interventions.\n", "\n", "================================================================================\n", "40. sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3)\n", "================================================================================\n", - "The species sR_IL6_sgp130, identified as mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 within the context provided, appears to involve components related to interleukin-6 (IL-6) signaling pathways. Here is the summary of the background based on the given context and general knowledge:\n", + "Based on the context provided, there is no specific mention of the species \"sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\" with the ID \"mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3.\" However, we can infer its role and importance based on the information regarding similar biological components described in the context.\n", + "\n", + "### Inferred Background Information on sR_IL6_sgp130:\n", "\n", - "### Biological Function\n", - "- **Fusion Protein**: The document mentions a fusion protein involving sgp130, which combines the extracellular portion of the gp130 protein with the Fc region of human IgG1. This fusion protein, known as sgp130Fc, is designed to inhibit IL-6 trans-signaling in cells.\n", + "1. **Biological Function:**\n", + " - The molecule seems to relate to the signaling pathway of IL-6 (Interleukin-6), a cytokine important in immune response.\n", + " - sR_IL6_sgp130 likely involves binding interactions similar to natural sgp130, which acts to inhibit IL-6 signaling by interfering with the IL-6/sIL-6R complex.\n", "\n", - "### Role in Pathways\n", - "- **IL-6 Trans-Signaling**: The primary role of sgp130Fc is to inhibit IL-6 trans-signaling. In the IL-6 signaling pathway, IL-6 can signal through its receptor complex involving IL-6R and gp130, leading to downstream effects such as the activation of STAT3 transcription factors. The fusion protein acts to prevent this signaling pathway by binding to the IL-6/sIL-6Rα complex.\n", - "- **Simulations in Crohn’s Disease**: The sgp130Fc protein is being studied for its therapeutic potential in inflammatory conditions like Crohn’s disease, where IL-6 signaling plays a significant role.\n", + "2. **Role in Pathways:**\n", + " - It may be involved in pathways such as IL-6 trans-signaling, which is mediated by the soluble IL-6 receptor (sIL-6R) and amplifies responses, particularly in diseases like Crohn's.\n", + " - It could potentially modulate signaling cascades involving STAT3 (Signal Transducer and Activator of Transcription 3), as IL-6 activates STAT3 through its receptor complexes.\n", "\n", - "### Interactions with Other Molecules\n", - "- **Binding with IL-6/sIL-6Rα Complex**: The sgp130Fc is assumed to bind with the IL-6/sIL-6Rα complex with affinities similar to natural sgp130. The presence of sgp130Fc in large quantities suggests it primarily functions by excess binding to this complex, thereby preventing excessive IL-6 signaling.\n", + "3. **Interactions with Other Molecules:**\n", + " - Likely interacts with components such as IL-6, sIL-6Rα, and sgp130 to modulate signaling.\n", + " - Its interaction may focus on forming a complex that either facilitates or inhibits further downstream signaling, affecting the activity of proteins like pSTAT3 (phosphorylated STAT3).\n", "\n", - "### Importance in the Biological System\n", - "- **Therapeutic Potential**: The document outlines the use of sgp130Fc as a potential therapeutic intervention in diseases with aberrant IL-6 signaling, such as Crohn’s disease. It has been shown to only be effective at very high doses due to its interaction landscape.\n", - "- **Limited Systemic Impact**: Due to high baseline levels of sgp130 compared to IL-6, small changes in sgp130 do not significantly affect the system, implying its role predominantly emerges under conditions requiring high-dose applications or alterations.\n", + "4. **Importance in the Biological System:**\n", + " - Given the high baseline level of sgp130 relative to free IL-6, sR_IL6_sgp130 may play a role in maintaining a steady state of signaling through sequestration of signaling complexes.\n", + " - Its importance could be in contexts requiring modulation of IL-6 activity, either as a natural response or therapeutic intervention, particularly in inflammatory conditions.\n", "\n", - "Overall, while the document primarily discusses the use of a related molecule (sgp130Fc), it emphasizes the relevance of sgp130 interactions within IL-6-related pathways, underscoring its importance in modulating immune and inflammatory responses within certain pathological contexts.\n", + "This inference is based on the role of similar molecules and the described importance of IL-6 signaling modulation in immunological and inflammatory contexts.\n", "\n", "================================================================================\n", "41. Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mwf7796221_1fea_4274_a93e_c00adbf5778c)\n", "================================================================================\n", - "Based on the provided context, there is no specific detailed information available about the species or molecule 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' with the ID mwf7796221_1fea_4274_a93e_c00adbf5778c. However, from the context and general knowledge, we can infer the following:\n", + "Based on the provided context, there is no direct or specific information about the species 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, we can infer what this species might be based on general knowledge about similar biological components mentioned in the context.\n", "\n", - "1. **Biological Function**: The document references serum antibody (Ab) concentrations in nmol/l, which suggests that 'Ab' likely stands for an antibody. Antibodies are proteins produced by the immune system to identify and neutralize pathogens such as bacteria and viruses.\n", + "From page 5 of the document, we see references to \"anti-IL-6 Ab\" and interactions with \"IL-6Rα/sIL-6Rα\" complexes, which suggest that 'Ab' could potentially be an antibody, possibly involved in targeting IL-6 or its receptor sIL-6Rα in the biological system being studied. \n", "\n", - "2. **Role in Pathways**: The context mentions anti-IL-6/sIL-6Rα interactions. Antibodies targeting the interleukin-6 (IL-6) pathway are typically used in treatments to modulate immune responses, particularly in inflammatory conditions. They can bind to IL-6 or its receptor to inhibit the downstream signaling pathway.\n", + "**Inferred Biological Function of Ab:**\n", + "- 'Ab' is likely an antibody that interacts with IL-6 or IL-6Rα. Antibodies are proteins produced by the immune system that can bind to specific antigens, such as proteins on pathogens or other molecules like interleukins.\n", "\n", - "3. **Interactions with Other Molecules**: The document discusses the anti-IL-6 Ab's effect in relation to IL-6 and sIL-6Rα. This suggests that the antibody in question interacts specifically with these cytokines or cytokine receptors, playing a role in reducing inflammation by interfering with the IL-6 signaling pathway.\n", + "**Role in Pathways:**\n", + "- The context mentions dose-response changes impacting serum CRP (C-reactive protein), indicating that 'Ab' might play a role in inflammatory pathways, particularly associated with modulating the immune response.\n", "\n", - "4. **Importance in the Biological System**: The antibody’s importance seems to be related to its therapeutic role in modulating the immune response, particularly in diseases involving heavy inflammation. This can include conditions like inflammatory bowel diseases or other autoimmune disorders, where targeting IL-6 or its receptor can have significant therapeutic effects.\n", + "**Interactions with Other Molecules:**\n", + "- If 'Ab' is an anti-IL-6 antibody, its primary interaction would be with interleukin-6 (IL-6) and its receptor complex, IL-6/sIL-6Rα. This interaction can impede the IL-6 signaling pathway, which is involved in inflammation and immune regulation.\n", "\n", - "In summary, based on the context and typical characteristics of antibodies in similar biological systems, 'Ab' is likely an antibody involved in targeting the IL-6 signaling pathway, important for managing inflammatory responses in various conditions.\n", + "**Importance in the Biological System:**\n", + "- The efficacy of 'Ab' in modulating serum CRP levels implies it holds significance in controlling inflammatory responses, potentially offering therapeutic benefits in conditions characterized by excessive inflammation, such as inflammatory bowel diseases or other chronic inflammatory conditions.\n", + "\n", + "This inferred role highlights the importance of 'Ab' in potentially therapeutic contexts where modulation of specific cytokine pathways is desired.\n", "\n", "================================================================================\n", "42. Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mw5d764bb8_5693_4ac8_9557_f65992cc5eb0)\n", "================================================================================\n", - "Based on the provided context, there is no specific mention or details about the species named 'Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, I can infer potential roles and functions based on adjacent biological components and typical interactions within such systems, especially considering the discussion around IL-6 pathways and related molecules in the context.\n", - "\n", - "1. **Biological Function**: In this particular study context, sIL-6R (soluble Interleukin-6 receptor) and IL-6 (a cytokine involved in inflammation and immune responses) are key components. Ab_sR might refer to an antibody-related soluble receptor component or variant. If related to IL-6/sIL-6R pathways, its function could involve modulation of immune responses or inflammation via binding interactions.\n", + "The context provided does not include any specific mention of the species named 'Ab_sR' (ID: mw5d764bb8_5693_4ac8_9557_f65992cc5eb0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5). Therefore, I will infer what this species might be based on general knowledge and the context provided.\n", "\n", - "2. **Role in Pathways**: The surrounding context heavily discusses the interaction of IL-6 with its receptor and the subsequent signaling pathways, such as the Jak-STAT pathway (notably leading to STAT3 activation), indicating a role in cytokine-receptor interactions. Ab_sR could interact within these pathways, perhaps as an intermediary or a modulator influencing signal transduction.\n", + "The context provided mentions interactions around IL-6, sIL-6R (soluble interleukin-6 receptor), and the IL-6/sIL-6R complex, which are significant components in the IL-6 signaling pathway. The mention of molecules such as CRP (C-reactive protein) suggests it is related to inflammatory responses.\n", "\n", - "3. **Interactions with Other Molecules**: If analogous to sIL-6R or anti-IL-6 therapeutic antibodies, Ab_sR might interact with IL-6, potentially modulating its effects by altered binding dynamics or competitive inhibition. Such interactions could influence downstream signaling events leading to transcriptional changes (e.g., expression of SOCS or CRP).\n", + "Given general biological knowledge, 'Ab_sR' could be hypothesized to represent an antibody or another protein involved in regulating or interacting with soluble receptors like sIL-6R. These soluble receptors often participate in signaling pathways where they modulate the activity of cytokines like IL-6.\n", "\n", - "4. **Importance in Biological System Being Modeled**: In systems modeling inflammatory responses, any component similar to an antibody interacting with cytokines like IL-6 is critical. It could predictively simulate treatment outcomes for inflammatory diseases or evaluate drug efficacy (e.g., CRP suppression in inflammatory cases). Ab_sR may hold similar significance if it's part of experimental or theoretical models assessing cytokine network modulation.\n", + "- **Biological Function**: 'Ab_sR' might function as a regulator in the IL-6 signaling pathway.\n", + "- **Role in Pathways**: It could play a role in modulating the inflammatory response or could be involved in the same pathway as IL-6/sIL-6R by affecting their interaction or function.\n", + "- **Interactions with Other Molecules**: It could potentially interact with IL-6, sIL-6R, or related complexes to modulate signaling and downstream effects such as CRP production.\n", + "- **Importance in the Biological System**: If it is analogous to components like antibodies or receptor regulators, its importance could lie in its potential to modulate immune responses and inflammation.\n", "\n", - "While these are educated guesses based on typical roles and interactions of analogous proteins within such biological systems, exact functions and roles of Ab_sR would be best determined by specifics from the cited source text.\n", + "Conclusively, without explicit details from the text, we extrapolate that 'Ab_sR' might be involved in related pathways and interactions as a regulatory molecule based on the IL-6/sIL-6R context and general knowledge of similar biological systems.\n", "\n", "================================================================================\n", "43. Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3) (ID: mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2)\n", "================================================================================\n", - "The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2) does not have specific background information provided explicitly in the context you shared. However, I can infer potential characteristics based on general knowledge about similar components.\n", - "\n", - "### Inferred Background Information:\n", + "Based on the provided context, there is no specific mention of the biological species or molecule named 'Ab_sR_IL6' (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3). However, we can infer some relevant details from the general context regarding IL-6 and related pathways.\n", "\n", - "1. **Biological Function:**\n", - " - 'Ab_sR_IL6' likely refers to an antibody ('Ab') targeting the soluble form of the interleukin-6 receptor (sIL-6R). This suggests it is involved in neutralizing or modulating the biological effects of sIL-6R, potentially inhibiting its interaction with interleukin-6 (IL-6).\n", + "1. **Biological Function**:\n", + " - IL-6 is a cytokine involved in various immune responses, inflammation, and hematopoiesis. In the provided context, it's part of the signaling pathways that modulate immune responses. \n", "\n", - "2. **Role in Pathways:**\n", - " - The context described the targeting of the IL-6/sIL-6R complex as a treatment strategy for conditions involving excessive IL-6 signaling, such as Crohn's disease. 'Ab_sR_IL6' might play a role in suppressing IL-6-mediated pathways, thereby reducing inflammation or immune responses associated with diseases like Crohn's disease or rheumatoid arthritis.\n", + "2. **Role in Pathways**:\n", + " - IL-6 interacts with its receptor, IL-6R, and the soluble form sIL-6Rα, to initiate signaling cascades involving pathways such as the JAK/STAT pathway (notably STAT3 phosphorylation). This can lead to the transcription of various genes, impacting inflammation and other immune responses.\n", + " - The mentioned pathways are part of a model studying IL-6 mediated immune regulation in diseases like Crohn’s disease, emphasizing IL-6's role in immune modulation.\n", "\n", - "3. **Interactions with Other Molecules:**\n", - " - Interacts with sIL-6R, preventing the formation of the IL-6/sIL-6R complex. This interaction would diminish the activity of the classical and trans-signaling pathways mediated by IL-6, leading to reduced activation of downstream signaling molecules like STAT3 and associated gene transcription.\n", + "3. **Interactions with Other Molecules**:\n", + " - IL-6 typically binds to its receptor IL-6R or its soluble form sIL-6Rα. This complex can further interact with a signaling receptor gp130 to trigger downstream signaling events.\n", + " - In therapeutic contexts, antibodies targeting IL-6 or IL-6Rα, such as tocilizumab, interrupt these interactions to modulate immune responses, particularly in inflammatory diseases.\n", "\n", - "4. **Importance in the Biological System Being Modeled:**\n", - " - Its importance lies in modulating inflammation by impacting IL-6 signaling. As IL-6 is crucial in immune response modulation, controlling its activity can lead to therapeutic benefits in diseases characterized by inflammation and immune dysregulation.\n", + "4. **Importance in the Biological System Being Modeled**:\n", + " - The provided context describes a model exploring IL-6/sIL-6Rα interactions, and their targeting implications for modulating immune responses in inflammatory conditions.\n", + " - The simulations suggest that targeting both IL-6 and the IL-6/sIL-6Rα complex can potentially enhance therapeutic outcomes, highlighting the importance of these interactions in therapeutic strategies.\n", "\n", - "Broadly, 'Ab_sR_IL6' serves as a critical component in therapeutic models aiming to attenuate aberrant IL-6 signaling pathways in immune-mediated diseases.\n", + "Therefore, if 'Ab_sR_IL6' is related to IL-6/IL-6R interactions, it might be an antibody or related agent involved in modulating these interactions, potentially playing a role in therapeutic interventions for diseases involving IL-6 dysregulation.\n", "\n", "================================================================================\n", "44. Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4) (ID: mwbc2f5464_81e5_43fd_8b39_f5a2756af72f)\n", "================================================================================\n", - "The provided context does not contain direct information specifically about the species 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, from the available information, we can infer some details based on the general context and related biological components mentioned:\n", + "The provided context does not explicitly mention specific background information or direct details about the species or molecule named 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, based on the surrounding context and general biological knowledge, some inferences can be made:\n", "\n", - "1. **Biological Function**: The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects like bacteria and viruses. They play a crucial role in targeting specific antigens for the immune response.\n", + "### Inferred Background Information:\n", + "1. **Biological Function:**\n", + " - The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins that play crucial roles in the immune system by identifying and neutralizing foreign objects such as bacteria and viruses.\n", + "\n", + "2. **Role in Pathways:**\n", + " - Given the context mentioning IL-6 and IL-6Rα, it is likely that this antibody might be involved in the immune response pathway, possibly targeting components like interleukin-6 (IL-6) or its receptor. This suggests its participation in pathways that modulate inflammation or immune signaling.\n", "\n", - "2. **Role in Pathways**: The context discusses the interaction between anti-IL-6 antibodies and IL-6/sIL-6Rα complex. IL-6 is a cytokine involved in inflammation and infection responses. Hence, antibodies targeting IL-6 pathways are often part of therapeutic interventions for inflammatory diseases.\n", + "3. **Interactions with Other Molecules:**\n", + " - The context suggests interaction or targeting of the IL-6 or IL-6 receptor (IL-6Rα), indicating that this antibody might bind to these molecules, influencing inflammatory processes or immune responses.\n", "\n", - "3. **Interactions with Other Molecules**: The document mentions the targeting of IL-6 and IL-6/sIL-6Rα complexes, suggesting that this antibody interacts with these molecules, likely inhibiting their function to reduce inflammation as indicated by the suppression of CRP (C-reactive protein), a marker of inflammation.\n", + "4. **Importance in the Biological System Being Modeled:**\n", + " - The system described seems to focus on understanding therapeutic strategies and modeling responses, possibly related to inflammatory diseases like inflammatory bowel diseases (IBDs) or conditions involving cytokines like IL-6. The antibody may be important for modulating these responses as part of a treatment strategy or for experimental observation.\n", "\n", - "4. **Importance in the Biological System Being Modeled**: The antibody's role appears to be significant in modulating inflammatory responses by targeting key molecular pathways involving IL-6 and its receptors. This indicates its potential therapeutic value in treating conditions where IL-6 is implicated, such as autoimmune or inflammatory diseases.\n", + "### General Inference:\n", + "- In systems biology, antibodies such as the one referred to, are often used experimentally or therapeutically to modulate biological pathways for research or treatment, particularly in immune response pathways dealing with cytokines. The context of IL-6 pathway targeting implies its significance in diseases managed by controlling inflammation, such as autoimmune or chronic inflammatory diseases. \n", "\n", - "In summary, while the antibody 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)' is not directly described in the context, inferred information suggests it likely functions as an IL-6 pathway inhibitor in an inflammatory response model, emphasizing its role in treatment strategies aimed at modulating immune responses.\n" + "This inferred summary is based on typical roles and interactions of antibodies in biological research and therapeutic contexts, especially within the immune signaling pathways referenced in the context.\n" ] } ], @@ -1711,222 +1716,222 @@ " 'name': 'IL6',\n", " 'original_name': 'IL6',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"The provided context outlines the biological function and role of IL-6, a cytokine important in the immune system. Based on the information:\\n\\n1. **Biological Function**:\\n IL-6 is a cytokine involved in immune regulation. It plays a crucial role in enhancing T-cell survival and resistance to apoptosis, particularly in the context of Crohn’s Disease, as well as in promoting chemokine secretion.\\n\\n2. **Role in Pathways**:\\n IL-6 signaling can proceed via two distinct pathways:\\n - The classical pathway, which involves the membrane-bound IL-6 receptor (IL-6Rα).\\n - The trans-signaling pathway, which involves a soluble IL-6 receptor (sIL-6Rα). In both pathways, IL-6 forms a complex with its respective receptor, which then recruits the gp130 coreceptor, leading to the formation of a hexameric receptor complex. This complex initiates phosphorylation of gp130-bound Janus kinase (Jak) proteins and subsequent activation of STAT3 (Signal Transducer and Activator of Transcription 3).\\n\\n3. **Interactions with Other Molecules**:\\n IL-6 interacts with its membrane-bound and soluble receptors to initiate signaling. The interaction sequence involves IL-6 binding to IL-6Rα, recruiting gp130, and activating downstream signaling molecules like Jak family proteins and STAT3.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n IL-6 is highlighted as a significant contributor in the pathophysiology of Crohn’s Disease due to its roles in promoting immune cell activities that lead to inflammation. The ability of IL-6 to engage in both classical and trans-signaling pathways suggests it is a versatile mediator in inflammatory processes, making it a critical target for therapeutic interventions.\\n\\n5. **General Knowledge and Inference**:\\n Beyond the context, IL-6 is generally known to be involved in inflammation and is a key player in various inflammatory diseases. It is a target for drugs like tocilizumab, which inhibit IL-6 signaling by preventing the interaction of IL-6 with its receptor, thus being an important therapeutic strategy in diseases such as rheumatoid arthritis.\\n\\nIn summary, IL-6 is a multifunctional cytokine central to immune regulation and inflammation, making it a crucial element in disease models, particularly those addressing inflammatory conditions like Crohn's Disease.\"},\n", + " 'background': \"Based on the provided context, IL6 (Interleukin 6) is a cytokine that plays a crucial role in immune regulation, particularly in the context of inflammatory conditions such as Crohn's disease and rheumatoid arthritis. \\n\\n### Biological Function:\\nIL6 is involved in immune responses and inflammation. It contributes significantly to the survival of T-cells and confers resistance to apoptosis in the lamina propria, a layer of the intestinal mucosa, thereby playing an important role in the pathology of inflammatory bowel diseases like Crohn's disease. It is also associated with elevated chemokine secretion.\\n\\n### Role in Pathways:\\nIL6 signaling can occur through two main pathways:\\n1. **Classical Pathway**: This involves the membrane-bound IL-6 receptor (IL-6Rα). In this process, IL6 binds to IL-6Rα on the cell membrane, forming a complex that recruits the membrane-bound coreceptor gp130, which forms a heterotrimeric complex. This complex dimerizes into a hexameric receptor complex, activating downstream signaling cascades.\\n2. **Trans-signaling Pathway**: Here, IL6 binds to a soluble form of IL-6Rα (sIL-6Rα), and this complex also recruits gp130, following a similar mechanism to form an active signaling complex. Trans-signaling is particularly important in pathological conditions where traditional signaling pathways are altered or less efficient.\\n\\n### Interactions with Other Molecules:\\nIL6 interacts with both membrane-bound and soluble forms of its receptor IL-6Rα to initiate signaling cascades. The activated receptor complex initiates phosphorylation of Janus kinase (Jak) family proteins, which subsequently phosphorylate signal transducer and activator of transcription 3 (STAT3). This signaling cascade is pivotal in mediating the biological effects of IL6 in inflammatory and immune responses. Additionally, the model demonstrates interactions between IL6, its receptors, and therapeutic antibodies like tocilizumab, which are designed to suppress IL6 signaling.\\n\\n### Importance in the Biological System Being Modeled:\\nIn the context of Crohn's disease, IL6 is highlighted as a significant mediator of immune regulation, particularly due to its role in enhancing T-cell survival and modulating chemokine secretion, which are key components of the disease's pathology. Targeting IL6 signaling pathways, whether through classical or trans-signaling, could be a therapeutic strategy for managing inflammatory responses associated with Crohn’s disease and similar conditions.\\n\\nIn summary, IL6 is a critical cytokine involved in immune regulation and inflammatory signaling, serving as both a potential target for therapeutic intervention and a key player in the pathogenesis of diseases such as Crohn's disease and rheumatoid arthritis.\"},\n", " {'id': 'mwbbbce920_e8dd_4320_9386_fc94bfb2fc99',\n", " 'name': 'sgp130',\n", " 'original_name': 'sgp130',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': 'Based on the context provided, sgp130 is a biological molecule that plays a role in inhibiting IL-6 trans-signaling. Here is a summary of its background information:\\n\\n1. **Biological Function**: sgp130 is derived from the extracellular portion of the gp130 protein. It serves to inhibit the signaling pathway of interleukin-6 (IL-6) by binding to the IL-6/sIL-6Rα complex, thereby preventing it from activating downstream signaling pathways. This inhibition is achieved by a fusion protein called sgp130Fc, which combines sgp130 with the Fc region of human IgG1.\\n\\n2. **Role in Pathways**: sgp130 influences the IL-6 signaling pathway, specifically targeting the trans-signaling aspect. IL-6 is a pro-inflammatory cytokine that can signal through a complex with soluble IL-6 receptor (sIL-6Rα) and gp130. By interfering with this pathway, sgp130 can modulate inflammatory responses.\\n\\n3. **Interactions with Other Molecules**: The primary interaction of sgp130 is with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 inhibits its ability to signal through the cell surface-bound gp130, thus blocking IL-6 mediated effects. The interaction between sgp130 and the IL-6/sIL-6Rα complex is central to its function.\\n\\n4. **Importance in the Biological System Being Modeled**: While sgp130 can effectively inhibit IL-6 trans-signaling, the context indicates that its role in the system being modeled is limited. The sensitivity analysis within the model shows that alterations in sgp130 levels have minimal effects on the steady-state values of output parameters due to the high baseline level of sgp130 compared to the relatively low concentration of free IL-6. This suggests that sgp130-based therapies may not be as impactful unless used at high and frequent doses. The model under discussion aimed at simulating its potential therapeutic use in conditions like Crohn’s disease.\\n\\nOverall, sgp130 is important for modulating IL-6 trans-signaling, but in the specific system modeled, its impact is limited under normal conditions due to its already high concentration compared to IL-6.'},\n", + " 'background': \"The species 'sgp130' appears to be related to a modified version of the gp130 protein, specifically referred to as sgp130Fc. Here is a summary based on the provided context:\\n\\n1. **Biological Function**: sgp130 is primarily involved in inhibiting IL-6 trans-signaling. This is achieved by its ability to bind to the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1, has been shown to inhibit this pathway in cultured cells.\\n\\n2. **Role in Pathways**: The primary pathway of interest involving sgp130 is the IL-6 signaling pathway. IL-6 is a cytokine implicated in various inflammatory processes, and its trans-signaling via the soluble IL-6 receptor (sIL-6Rα) is distinct from classical signaling. The role of sgp130 is to regulate this trans-signaling pathway by competing with cell surface gp130 receptors, thereby reducing the pro-inflammatory effects mediated by IL-6/sIL-6Rα.\\n\\n3. **Interactions with Other Molecules**: sgp130 interacts with the IL-6/sIL-6Rα complex. In the presence of high amounts of sgp130, most of the IL-6 is bound, thus preventing it from mediating its effects via the trans-signaling pathway.\\n\\n4. **Importance in the Biological System**: Despite its potential therapeutic role, the sensitivity analysis from the provided context suggests that sgp130 has a relatively low impact on the steady-state dynamics of the system being modeled. This is attributed to its high baseline concentration compared to IL-6, implying that large changes in sgp130 levels are needed to achieve significant biological effects. Therefore, the efficacy of sgp130-based therapies, like sgp130Fc, may be limited and require high doses to be effective.\\n\\nOverall, sgp130 serves as a regulatory molecule within the IL-6 signaling pathway, specifically targeting and mitigating the effects of IL-6 trans-signaling, though its standalone therapeutic potential may be limited due to high baseline levels and lower impact on system sensitivity.\"},\n", " {'id': 'mw810ff751_fa4e_4143_bd50_169b3e325e1e',\n", " 'name': 'sR_IL6_sgp130',\n", " 'original_name': 'sR_IL6_sgp130',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"Based on the provided context from the document, 'sR_IL6_sgp130' seems to be a part of the IL-6 signaling pathway and is likely a reference to a complex involving soluble IL-6 receptor components. Here's a summary based on the information provided and general knowledge:\\n\\n- **Biological Function:** The complex is involved in modulating IL-6 signaling, particularly influencing the trans-signaling mechanism. Soluble gp130 (sgp130) acts as a natural inhibitor of IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing it from associating with membrane-bound gp130, which is necessary for signal transduction.\\n\\n- **Role in Pathways:** It is a critical modulator in the IL-6 signaling pathway. Normally, IL-6 binds to the soluble IL-6 receptor (sIL-6R), and this complex can further engage with gp130 on cell surfaces to propagate downstream signaling events. The sgp130 serves as a sink for these IL-6/sIL-6R complexes, limiting their ability to bind to cellular gp130 and hence reducing downstream signaling such as STAT3 activation.\\n\\n- **Interactions with Other Molecules:** The complex interacts primarily with IL-6 and its soluble receptor (sIL-6R). It prevents these molecules from engaging with cell-surface gp130, thus acting as a competitive inhibitor in the pathway.\\n\\n- **Importance in the Biological System:** In the context of the system being modeled, sgp130 is crucial as it regulates the balance of IL-6 signaling. Its high baseline concentration relative to IL-6 suggests it plays a stabilization role in keeping the system responsive only to significant changes in IL-6 levels. However, its effectiveness as a therapeutic agent, such as in Crohn’s disease, may require high and frequent dosing due to its large baseline presence and minimal effect on system dynamics under normal conditions.\\n\\nNo direct information about 'sR_IL6_sgp130' as a separate distinct entity is found in the context, suggesting it might be inferred from understanding sgp130's complex with IL-6 and sIL-6R within the described signaling and therapeutic contexts.\"},\n", + " 'background': \"The species 'sR_IL6_sgp130' appears to be involved in the system of IL-6 signaling, which plays a critical role in inflammatory responses such as those found in diseases like Crohn's disease. Based on the provided context, here's a summary of its background information:\\n\\n1. **Biological Function**: sR_IL6_sgp130 is likely related to the IL-6 signaling pathway. It is suggested to be a complex involving soluble IL-6 receptor (sIL-6R) and sgp130, which is a fusion protein comprised of the extracellular portion of the gp130 receptor and the Fc region of human IgG1. The gp130 receptor is part of the signaling pathway for IL-6, a cytokine involved in immune responses.\\n\\n2. **Role in Pathways**: sR_IL6_sgp130 is involved in the inhibition of IL-6 trans-signaling. This pathway is crucial for mediating pro-inflammatory responses. The context suggests that sgp130 can bind to the IL-6/sIL-6Rα complex, potentially blocking further signaling within this pathway.\\n\\n3. **Interactions with Other Molecules**: The species interacts with IL-6 and sIL-6Rα. The fusion protein sgp130Fc has been shown to bind to the IL-6/sIL-6Rα complex, suggesting that sR_IL6_sgp130 may act to sequester this complex and prevent it from engaging with cell surface receptors, thereby inhibiting downstream signaling, including pSTAT3 activation.\\n\\n4. **Importance in the Biological System Being Modeled**: Despite its role in inhibiting IL-6 signaling, sensitivity analyses indicate that altering sgp130 levels has a minimal effect on the steady-state dynamics of the system due to its high baseline concentration. This suggests that while sR_IL6_sgp130 has the potential to influence inflammation pathways, its impact may be limited under normal conditions and would require significant changes to yield observable effects. \\n\\nOverall, sR_IL6_sgp130 represents an important therapeutic target or molecule within the context of IL-6 mediated diseases, but its natural abundance and resultant low system sensitivity under basal conditions make it a challenging target for effective therapeutic intervention without substantial dosage alterations.\"},\n", " {'id': 'mw114aa90f_5f5b_4fe8_9406_361c8489b6a1',\n", " 'name': 'CRP',\n", " 'original_name': 'CRP',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"The term 'CRP' within the context provided refers to C-reactive protein, rather than a distinct biological species. C-reactive protein is a well-known biomarker present in the bloodstream, often used to assess inflammation within the body. Here's a summary of relevant background information about CRP based on the context and general biological understanding:\\n\\n- **Biological Function**: C-reactive protein is an acute-phase protein produced by the liver in response to inflammation. Its primary role is to bind to the surface of dead or dying cells (and some types of bacteria) to activate the complement system, thereby promoting phagocytosis by macrophages. This function is part of the body's innate immune response, aiding in clearing pathogens and dead cells from the bloodstream.\\n\\n- **Role in Pathways**: CRP is part of the body's acute-phase response to inflammation. Its levels in the blood increase rapidly in response to inflammatory cytokines, such as interleukin-6 (IL-6). This makes CRP an integral component in pathways related to the immune system's response to infection, injury, or chronic inflammatory diseases.\\n\\n- **Interactions with Other Molecules**: CRP interacts with the complement system components, particularly C1q, to initiate the complement cascade, a series of reactions that help eliminate pathogens. It also interacts with receptors on the surfaces of immune cells, such as Fcγ receptors, facilitating opsonization and phagocytosis. The document mentions interactions with IL-6 and its receptor IL-6Rα, as CRP production is highly influenced by IL-6 signaling.\\n\\n- **Importance in Biological Systems**: In the context of the model described, CRP is used as a biomarker to assess inflammation levels in patients, particularly those with conditions such as Crohn's disease. The model measures CRP levels to validate its predictions regarding drug effects on inflammatory pathways, highlighting its utility in monitoring disease activity and treatment efficacy.\\n\\nOverall, CRP is a crucial component in biological models focused on inflammatory diseases due to its rapid and measurable response to changes in underlying inflammation.\"},\n", + " 'background': \"C-reactive protein (CRP) is a crucial protein in the context of inflammation and immune response regulation. Based on the provided context and general knowledge about CRP, the following summarizes its biological role and significance:\\n\\n1. **Biological Function**:\\n - CRP is an acute-phase protein, primarily produced in the liver in response to inflammation. It is commonly used as a marker to assess inflammatory states in various conditions. The production is typically induced by cytokines such as interleukin-6 (IL-6).\\n\\n2. **Role in Pathways**:\\n - CRP plays a part in the systemic response to inflammation, often used clinically as an indicator for inflammatory conditions such as infections and autoimmune diseases. In the context described, CRP levels are used to monitor and model the effect of treatments targeting components of the IL-6 signaling pathway, especially in diseases like Crohn's disease.\\n\\n3. **Interactions with Other Molecules**:\\n - CRP interacts with various components of the immune system. It can bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system, promoting phagocytosis by macrophages, which is a crucial aspect of its role in inflammation.\\n - In the context of the presented data, CRP levels are modulated through pathways involving IL-6 and its receptor (IL-6Rα), showcasing its interconnected role in immune signaling pathways.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n - Within the model described, CRP serves as a key biomarker for the effectiveness of treatment strategies targeting IL-6 signaling. The modulation of CRP levels indicates the level of inflammation and the success of therapeutic interventions aimed at reducing inflammation by inhibiting IL-6 activity.\\n - The document suggests the use of CRP levels to validate and predict the outcomes of therapeutic interventions, underlining its importance as a measurable outcome in clinical and modeling studies.\\n\\nOverall, CRP acts as an essential biomarker and participant in inflammatory pathways, and its levels are indicative of the inflammatory state and the impact of medical treatments in the studied model.\"},\n", " {'id': 'mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc',\n", " 'name': 'sR',\n", " 'original_name': 'sR',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"Based on the provided context, the species named 'sR' (ID: mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc) is likely related to the IL-6 signaling pathway. However, specific details about 'sR' are not provided directly in the context. Given that 'sR' is mentioned alongside IL-6, sIL-6R, and sgp130, it could be inferred that 'sR' is a component or modifier in the interleukin-6 (IL-6) signaling pathway.\\n\\n### Inferred Background Information\\n\\n**Biological Function**:\\n- It is probable that 'sR' is related to IL-6 signaling, potentially as a soluble receptor or co-receptor. Soluble receptors often exist as naturally occurring antagonists or helpers of cytokine signaling, modulating the pathway's activity.\\n\\n**Role in Pathways**:\\n- 'sR' might be involved in modulating the availability or activity of IL-6, similar to how sgp130 and sIL-6R work. sIL-6R is known to allow cells that do not possess membrane-bound IL-6R to respond to IL-6 through a process known as trans-signaling.\\n\\n**Interactions with Other Molecules**:\\n- It may interact with IL-6 or IL-6 receptor complexes. This interaction is crucial in the modulation of the pathway, likely affecting the downstream signaling events such as the activation of STAT3 (Signal Transducer and Activator of Transcription 3).\\n\\n**Importance in the Biological System**:\\n- Given its potential role in cytokine signaling, 'sR' would be important in regulating inflammatory responses, immune system signaling, and possibly in the pathophysiology of diseases where IL-6 is a key player, such as autoimmune diseases.\\n\\n### Contextual Consideration\\n- The provided context includes a discussion on sensitivity analysis and the role of sgp130 with IL-6, which highlights the intricate balance within the cytokine signaling pathways. Though 'sR' is not explicitly expanded upon, understanding the dynamics of similar molecules like sIL-6R and sgp130 offers insights into its potential biological significance.\\n \\nThis inferred information aligns with typical roles of soluble cytokine receptors in biological systems. However, the exact nature and function of 'sR' would require further specific details or experimental data.\"},\n", + " 'background': \"Based on the provided context, there is limited direct information regarding the species 'sR' with ID mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc. However, we can infer some details based on the context of similar biological components mentioned.\\n\\n1. **Biological Function**: The context does not specify a unique biological function for 'sR'. However, it mentions interactions involving IL-6 and sIL-6R, suggesting that 'sR' might be associated with receptor or signaling functions in the IL-6 pathway. sIL-6R usually stands for soluble IL-6 receptor, which is involved in extending the effects of the IL-6 cytokine beyond cells that have membrane-bound receptors.\\n\\n2. **Role in Pathways**: Similar to sIL-6R and other molecules like sgp130, 'sR' might play a role in the modulation of signaling pathways. IL-6 signaling pathways involve activation and modulation through receptors, influencing gene transcription and protein production. It's plausible that 'sR' participates in similar pathways, potentially affecting signal transduction and biological responses.\\n\\n3. **Interactions with Other Molecules**: Although not directly mentioned, 'sR' perhaps interacts with other components in the IL-6 signaling cascade such as IL-6, its receptors (like IL-6R), and possibly soluble receptors like sgp130. Intermediates such as Jak and STAT3 are common in such pathways, and 'sR' might influence or be influenced by these interactions.\\n\\n4. **Importance in the Biological System**: The significance of 'sR' is not explicitly described, but it could be an important regulator within the system. Given the extensive discussion on IL-6 and its modulation by soluble receptors and sgp130, 'sR' might contribute to these dynamics, affecting cellular responses to IL-6 signaling and influencing conditions like inflammatory responses or chronic disease states.\\n\\nIn summary, while not directly detailed, 'sR' may operate similarly to other receptors or molecules in the IL-6 signaling context, playing a part in modulation, interaction, and systemic effects within biological pathways.\"},\n", " {'id': 'mw03db56ac_8dc6_4931_ae82_fef706d2ee3d',\n", " 'name': 'sR_IL6',\n", " 'original_name': 'sR_IL6',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': 'The species labeled \\'sR_IL6\\' in the context provided appears to refer to a soluble receptor for interleukin-6 (IL-6), often denoted as sIL-6R. Soluble IL-6 receptors play a crucial role in IL-6 trans-signaling pathways, which differ from classical signaling by involving the soluble receptor form (sIL-6R) rather than the membrane-bound IL-6 receptor (IL-6R).\\n\\n### Biological Function:\\n- **Soluble IL-6 Receptor (sIL-6R):** Its primary function is to bind to the cytokine IL-6, forming a complex that can activate cells that do not have membrane-bound IL-6 receptors. This process is known as \"trans-signaling\" and allows for a wider range of cells to respond to IL-6, expanding its biological effects.\\n\\n### Role in Pathways:\\n- **Trans-signaling Pathway:** In trans-signaling, the IL-6/sIL-6R complex associates with the membrane protein gp130, facilitating intracellular signaling cascades such as the JAK/STAT pathway. This activation leads to gene transcription and biological responses in target cells.\\n- **Classical Signaling Pathway:** sIL-6R is involved in sequestering IL-6 in the presence of the regulatory protein sgp130, modulating the signaling capacity by preventing excessive inflammatory signaling.\\n\\n### Interactions with Other Molecules:\\n- **IL-6:** The soluble receptor interacts with IL-6 to initiate trans-signaling.\\n- **gp130:** Binds the IL-6/sIL-6R complex, essential for downstream signal transduction.\\n- **sgp130:** Acts as a natural inhibitor by sequestering IL-6/sIL-6R complexes, dampening potential overactivation of IL-6 signaling.\\n\\n### Importance in the Biological System:\\nIn the context of Crohn\\'s disease and immune regulation, the IL-6/sIL-6R complex plays a critical role. Modulating this pathway can influence disease progression and therapeutic outcomes. Targeting the IL-6/sIL-6R complex could offer promising treatments by adjusting the immune response and inflammation characteristic of the condition.\\n\\nThe context suggests that sIL-6R could be involved in a model for chronic inflammatory conditions, highlighting its significance in promoting or inhibiting inflammation through different signaling pathways. By understanding its interactions and functions, potential strategies can be developed for therapeutic interventions, such as using antibodies to modify its activity.'},\n", + " 'background': 'The species \"sR_IL6,\" identified by the ID mw03db56ac_8dc6_4931_ae82_fef706d2ee3d, is likely related to the soluble interleukin-6 receptor (sIL-6R) based on the context provided. Here is an interpretation and breakdown of its role and function:\\n\\n1. **Biological Function**: \\n - sR_IL6 is likely analogous to sIL-6R, which functions as a part of the IL-6 signaling pathway. The soluble receptor binds to interleukin-6 (IL-6), facilitating its interaction with gp130, an essential component for signal transduction.\\n\\n2. **Role in Pathways**:\\n - IL-6 can signal through classical and trans-signaling pathways. In the classical pathway, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), while in the trans-signaling pathway, the soluble receptor (sIL-6R) binds IL-6, allowing the complex to interact with gp130 on cells that do not express IL-6R. This interaction is crucial for activating downstream signaling pathways, such as the JAK/STAT pathway, specifically promoting STAT3 phosphorylation (pSTAT3), which can lead to gene transcription including the acute phase protein C-reactive protein (CRP).\\n\\n3. **Interactions with Other Molecules**:\\n - sR_IL6 (sIL-6R) interacts directly with IL-6 to form the IL-6/sIL-6R complex. This complex can be sequestered by the soluble gp130 (sgp130), inhibiting the signaling and potentially modulating the intensity or range of the IL-6 mediated response.\\n\\n4. **Importance in the Biological System**:\\n - The IL-6/sIL-6R complex plays a role in immune regulation, as indicated by its involvement in models studying conditions like Crohn’s disease. It has significance in how inflammation is managed within the body, especially in the context of inflammatory diseases.\\n - The model indicates the regulation of sR_IL6 levels may impact therapeutic strategies, with alterations in dosages of anti-IL-6 antibodies showing variable efficacy.\\n\\nOverall, the sR_IL6 is a critical component in mediating IL-6 trans-signaling, thus having a significant impact on immune regulation and potential therapeutic strategies for inflammatory diseases.'},\n", " {'id': 'mwf345ed7a_0622_403c_b816_c8749a2c9ded',\n", " 'name': 'Ab',\n", " 'original_name': 'Ab',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"Based on the provided documents, there isn't direct and specific information regarding the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded) in the given context. However, based on general knowledge and context clues, 'Ab' likely refers to an antibody, given the reference to serum Ab concentrations and interaction with IL-6 and sIL-6Rα complexes.\\n\\n1. **Biological Function**: Antibodies (Ab) are proteins produced by the immune system that recognize and bind to specific antigens, such as pathogens (viruses, bacteria) or other target molecules. Their primary function is to neutralize these antigens and facilitate their destruction by other immune cells.\\n\\n2. **Role in Pathways**: In the context provided, 'Ab' is involved in targeting the IL-6 and IL-6Rα pathways. This is indicative of its role in modulating inflammatory responses, likely through the inhibition of the IL-6 signaling pathway.\\n\\n3. **Interactions with Other Molecules**: The document mentions the anti-IL-6 Ab dose response and its effects on serum CRP suppression. The interaction specifically involves the binding of the antibody to IL-6 and the IL-6/sIL-6Rα complex, which suggests its use in blocking or reducing the inflammatory signaling mediated by these molecules.\\n\\n4. **Importance in the Biological System**: The blocking or modulation of IL-6 signaling by antibodies plays a significant role in managing inflammatory diseases. The context implies that targeting IL-6 and its receptor complexes can be part of a therapeutic strategy for conditions characterized by excessive inflammation, such as inflammatory bowel diseases.\\n\\nGiven these points, 'Ab' in this context seems to be associated with therapeutic antibodies used to manage inflammation by interfering with specific cytokine pathways, particularly involving IL-6. This type of intervention is crucial in diseases where cytokine signaling contributes to the pathology.\"},\n", + " 'background': \"Based on the provided context from the documents, the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded, located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e) is likely referring to an antibody, given the context in which it's mentioned, particularly in relation to drug doses and targeting of specific molecular complexes.\\n\\nHere are the inferred details about 'Ab' based on the context:\\n\\n- **Biological Function**: The antibody ('Ab') likely functions in binding to specific target molecules, probably related to the immune system or inflammation pathways, as inferred from the association with IL-6/sIL-6Rα complexes—the interleukin-6 receptor alpha complex.\\n\\n- **Role in Pathways**: 'Ab' seems to play a role in modulating pathways related to inflammatory responses, especially through interactions with the IL-6 signaling pathway. It appears to be part of a therapeutic strategy, potentially targeting cytokines such as IL-6 and its soluble receptor complex to regulate inflammation, as noted by the mention of CRP suppression (C-reactive protein—a marker for inflammation).\\n\\n- **Interactions with Other Molecules**: The context suggests a role in interacting with IL-6 and sIL-6Rα complexes. The antibody serves as a limiting factor in neutralizing or modulating these complexes within the biological system, influencing serum biomarker levels like CRP.\\n\\n- **Importance in the Biological System Being Modeled**: 'Ab' is significant in the modeled system as a therapeutic agent, potentially used in treating inflammatory conditions by targeting cytokine pathways. By affecting IL-6-related pathways, it appears to reduce inflammatory responses, as evidenced by experiments and modeling of serum CRP suppression following treatments.\\n\\nThough specific details about 'Ab' are not explicitly provided in the excerpts, it can be inferred that 'Ab' is a therapeutic antibody with a function in targeting pro-inflammatory cytokine pathways within the given biological context, aiming to control or reduce inflammatory processes.\"},\n", " {'id': 'mw1da111f2_a036_4392_8512_015005bdcbb7',\n", " 'name': 'Ab_sR',\n", " 'original_name': 'Ab_sR',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"The specific species 'Ab_sR' (ID: mw1da111f2_a036_4392_8512_015005bdcbb7) located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e does not seem to be explicitly mentioned in the provided context. However, based on the context and general knowledge, we can infer some relevant background information about similar biological components that usually appear in such contexts. \\n\\nThe context mentions components such as sIL-6R, IL-6, and their interactions, which are indicative of a role in inflammatory response pathways. sIL-6R is a soluble form of the IL-6 receptor, and it typically participates in what's known as IL-6 trans-signaling. In this process, instead of the membrane-bound receptor, IL-6 binds to sIL-6R to form a complex that can interact with the gp130 protein, initiating signaling cascades even in cells that do not express the full receptor. This mechanism is important in regulating immune responses, inflammation, and possibly chronic inflammatory diseases by influencing the production of acute-phase proteins like C-reactive protein (CRP).\\n\\nGiven this understanding, 'Ab_sR' could potentially refer to an antibody or an interaction factor related to the soluble receptor pathways, possibly playing a regulatory or inhibitory role in these pathways through binding interactions. Its importance might then be deduced from its capability to modulate these signaling pathways, with potential therapeutic implications for diseases driven by excessive IL-6 signaling.\\n\\nIf Ab_sR is an antibody, it could play a role similar to antibodies against IL-6 or IL-6Rα, aiming to disrupt or modify these signaling pathways, potentially reducing inflammatory responses as a therapeutic strategy. Such antibodies are being explored in contexts of autoimmune diseases, cancers, and inflammatory disorders. \\n\\nNote: This inference is made based on the context provided and common biological functions of related components. Further specific information would be required for more accurate detailing of Ab_sR's role.\"},\n", + " 'background': 'Based on the provided context, specific information about the species \"Ab_sR\" (ID: mw1da111f2_a036_4392_8512_015005bdcbb7, located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e) is not directly mentioned. However, we can infer its potential role and importance in the biological system being modeled by examining the surrounding biological components and pathways mentioned in the context.\\n\\n### Inferred Background Information about Ab_sR\\n\\n1. **Biological Function:**\\n - The context suggests a focus on interleukin-6 (IL-6) and its receptor interactions, particularly involving the soluble IL-6 receptor (sIL-6R) and its complexes. Given the naming convention \"Ab_sR,\" it is reasonable to infer that Ab_sR could represent an antibody (Ab) specific to a soluble receptor (sR), likely related to the IL-6 signaling pathway.\\n\\n2. **Role in Pathways:**\\n - The IL-6 signaling pathway involves several key interactions, including the formation of complexes with sIL-6R, which are critical for signal transduction. Ab_sR might participate in modulating or inhibiting this pathway, possibly by binding to the sIL-6R or other pathway components, potentially altering the pathway\\'s output like the downstream effects on C-reactive protein (CRP) production.\\n\\n3. **Interactions with Other Molecules:**\\n - Within the pathway context, Ab_sR may interact with IL-6, sIL-6R, and possibly other related components like the glycoprotein (gp130), which are crucial for IL-6 signal transduction. Its role might be to bind these molecules to modulate their activity or bioavailability in the system, akin to the action of therapeutic antibodies that target cytokine receptors.\\n\\n4. **Importance in the Biological System:**\\n - Ab_sR could be significant for fine-tuning the inflammatory response mediated by IL-6 signaling. By regulating or inhibiting the function of the IL-6/sIL-6R pathway, Ab_sR might contribute to controlling inflammation and related processes in tissues such as the liver and gastrointestinal tract. This modulation could be especially important in conditions where IL-6 plays a pivotal role, such as in autoimmune diseases or chronic inflammatory states.\\n\\nOverall, while direct information on Ab_sR is not available, the context allows us to hypothesize its role as a regulatory or inhibitory agent within the IL-6 signaling pathway, potentially serving as a therapeutic molecule targeting inflammation-related pathways.'},\n", " {'id': 'mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac',\n", " 'name': 'Ab_sR_IL6',\n", " 'original_name': 'Ab_sR_IL6',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': \"The context provided does not directly specify information about a species named 'Ab_sR_IL6'. However, based on general knowledge and the context given, we can make some inferences and provide related information:\\n\\n1. **Biological Function**: Given the naming convention used ('Ab_sR_IL6'), it is likely that this refers to an antibody (Ab) targeting a soluble receptor (sR) for interleukin-6 (IL-6), possibly inhibiting its action. IL-6 is a cytokine involved in inflammatory and immune responses.\\n\\n2. **Role in Pathways**: IL-6 typically signals through its receptor complex, including IL-6R and gp130, to activate downstream signaling pathways like JAK/STAT, leading to the activation of transcription factors such as STAT3. This cascade leads to the expression of various genes involved in inflammation and immune regulation.\\n\\n3. **Interactions with Other Molecules**: Based on the context, the antibody could be interacting with the IL-6/sIL-6R complex to modulate its effects. The text describes interactions involving sIL-6R and IL-6, potentially including competition or inhibition by antibodies that alter the signaling outcomes and inflammatory responses.\\n\\n4. **Importance in the Biological System Being Modeled**: In the context of the model described, inhibiting the IL-6/sIL-6R interaction is a focus, likely due to its role in conditions like Crohn's Disease or rheumatoid arthritis. Modifying this pathway's activity through an antibody such as 'Ab_sR_IL6' might be of therapeutic significance, potentially helping to suppress excessive inflammatory responses, as suggested by the interest in CRP (C-reactive protein) suppression and dose-response relationships.\\n\\nIn summary, 'Ab_sR_IL6' is likely conceptualized as an antibody targeting the soluble IL-6 receptor to interfere with IL-6 mediated signaling pathways, which are pivotal in certain inflammatory diseases. While specific details are not provided in the context, this inference aligns with common therapeutic strategies involving cytokine signaling modulation.\"},\n", + " 'background': \"Based on the context provided, there is no specific mention of the species 'Ab_sR_IL6' by name. However, the context revolves around interactions involving IL-6, its receptor sIL-6Rα, and antibodies targeting these molecules. We can infer certain characteristics and roles this species might fulfill based on the general knowledge of similar biological components and the information presented:\\n\\n1. **Biological Function**: Proteins associated with the suffix 'Ab' usually refer to antibodies. Given the context, 'Ab_sR_IL6' likely functions as an antibody targeting the IL-6 receptor, specifically the soluble form sIL-6Rα. Antibodies like these are typically designed to bind to their target receptor, potentially blocking its interaction with its ligand (IL-6) or other molecules, resulting in modulation of a biological pathway.\\n\\n2. **Role in Pathways**: In the immune regulation context, this antibody likely plays a role in modulating IL-6-mediated signaling pathways. The data discusses targeting the IL-6/sIL-6Rα complex to modulate responses in the immune system, particularly in inflammatory conditions like Crohn’s Disease and rheumatoid arthritis. By interfering with this pathway, the antibody likely serves to suppress the pro-inflammatory effects mediated by IL-6.\\n\\n3. **Interactions with Other Molecules**: The document specifically talks about the interaction of antibodies with sIL-6Rα and IL-6, suggesting that 'Ab_sR_IL6' could interact with these components. The interaction with sIL-6Rα likely prevents the receptor from associating with IL-6 or gp130 (another crucial signaling component). This interference can result in reduced signaling through the JAK-STAT pathway, which is implicated in inflammation and autoimmune disease processes.\\n\\n4. **Importance in the Biological System**: The importance of such an antibody in the model is likely related to its ability to control inflammatory processes. By targeting sIL-6Rα, it could help reduce the production of inflammatory mediators like C-reactive protein (CRP) and other gene products important in the inflammatory response. In the context of diseases like Crohn’s Disease, the use of such an antibody could be significant for reducing symptoms and controlling disease progression.\\n\\nGiven these points, 'Ab_sR_IL6' likely represents a therapeutic antibody targeted towards IL-6 signaling components, playing a crucial role in modulating immune responses in inflammatory diseases.\"},\n", " {'id': 'CRP_Suppression___',\n", " 'name': 'CRP Suppression (%)',\n", " 'original_name': 'CRP Suppression (%)',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': 'Based on the context provided, \"CRP Suppression (%)\" refers to the measurement of the reduction in serum C-reactive protein (CRP) levels. CRP is a biological marker of inflammation, and its levels can be indicative of inflammatory responses in the body. Understanding the suppression of CRP levels has the following implications:\\n\\n1. **Biological Function**: CRP is an acute phase protein, produced by the liver in response to inflammation. It plays a role in the body\\'s immune response, indicating tissue damage or inflammation.\\n\\n2. **Role in Pathways**: CRP is involved in the inflammatory pathway. Suppressing CRP levels typically suggests an underlying modulation of the inflammatory response, often facilitated through interventions like antibodies targeting specific inflammatory cytokines or receptors, such as IL-6 or IL-6Rα in this context.\\n\\n3. **Interactions with Other Molecules**: The context implies interactions with Interleukin-6 (IL-6) and its receptor (IL-6Rα). Treatments with anti–IL-6 or anti–IL-6Rα antibodies reduce CRP levels, thereby modulating inflammation, as indicated by the provided data on drug dose and CRP suppression.\\n\\n4. **Importance in the Biological System**: Suppression of serum CRP is an important indicator of the efficacy of drugs, like anti-IL-6 or anti-IL-6Rα antibodies, in reducing inflammatory responses. This makes CRP suppression a critical measure for evaluating the outcome of therapeutic interventions aimed at inflammatory diseases.\\n\\nWhile the context does not directly describe CRP Suppression (%) as a biological species, it is a measure of the effectiveness of treatments targeting inflammatory pathways. Interactions that lead to its suppression are essential for understanding therapeutic impacts on inflammation-related conditions.'},\n", + " 'background': \"CRP Suppression (%) refers to the extent to which the levels of C-reactive protein (CRP) in the serum are reduced from baseline levels. CRP is a biomarker typically used to assess inflammation and is often elevated in response to inflammatory conditions such as infections, chronic diseases, or autoimmune disorders.\\n\\n### Biological Function:\\n- **C-reactive protein (CRP):** CRP is a protein produced by the liver in response to inflammation. It is part of the body's immune response and acts as an opsonin, marking pathogens for destruction by immune cells.\\n\\n### Role in Pathways:\\n- **Inflammatory Pathways:** The suppression of CRP levels is a marker of reduced inflammation. In the context of treatments targeting cytokines like interleukin-6 (IL-6), the decrease in CRP is an indicator of the efficacy of such anti-inflammatory treatments.\\n\\n### Molecular Interactions:\\n- **Interaction with Interleukin-6 (IL-6):** IL-6 is a cytokine that stimulates CRP production. Anti-IL-6 or anti-IL-6 receptor therapies aim to reduce CRP levels by blocking the action of IL-6, thereby diminishing its signal for CRP synthesis.\\n\\n### Importance in the Biological System Being Modeled:\\n- **Treatment Efficacy Marker:** CRP Suppression (%) is used as a biomarker to evaluate the effectiveness of treatments, such as anti-IL-6 antibodies or anti-IL-6R antibodies, in reducing inflammation. The suppression percentage directly correlates with the reduction in inflammatory activity within the body.\\n- **Dose-response Analysis:** The relationship between drug dosage and CRP Suppression (%) is crucial for determining optimal dosing regimens. Increased CRP suppression with higher doses of anti-inflammatory drugs typically indicates greater efficacy, though it may plateau or saturate at certain dose levels.\\n\\nIn summary, CRP Suppression (%) serves as a critical indicator for assessing the impact of therapeutic strategies aimed at managing inflammatory responses by targeting specific immune signaling pathways in the body.\"},\n", " {'id': 'CRP____of_baseline',\n", " 'name': 'CRP (% of baseline)',\n", " 'original_name': 'CRP (% of baseline)',\n", " 'compartment': 'mw53ffe9e6_beef_45c4_90a5_a79197ed506e',\n", - " 'background': 'The term \"CRP (% of baseline)\" is referring to C-reactive protein (CRP) levels measured as a percentage of a baseline value. In the context provided, it appears to be a metric used in the modeling and analysis of clinical trial data related to anti–IL-6Rα antibody treatments, specifically tocilizumab, which is an anti-inflammatory medication. Here\\'s a summary based on the context and general knowledge about CRP:\\n\\n1. **Biological Function:**\\n - CRP is a protein produced by the liver in response to inflammation. It is part of the acute phase response to inflammation and is a biomarker commonly used to assess inflammation and tissue injury.\\n\\n2. **Role in Pathways:**\\n - CRP is a key player in the acute inflammatory response and is involved in pathways that react to injury, infection, and inflammation. It interacts with the immune system to facilitate the clearance of necrotic and apoptotic cells and bacteria.\\n\\n3. **Interactions with Other Molecules:**\\n - CRP levels are influenced by the presence of pro-inflammatory cytokines, particularly interleukin-6 (IL-6). This context highlights the interaction between CRP levels and anti–IL-6Rα antibodies, which inhibit IL-6 signaling and therefore can suppress CRP production as part of their therapeutic action.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - In the given context, CRP (% of baseline) serves as an important biomarker for evaluating the efficacy of tocilizumab treatment in suppressing inflammation. The model uses CRP levels to compare and validate simulation results against clinical trial data, indicating its critical role in assessing treatment impacts.\\n\\nNo specific unique details beyond this general framework are detailed in the context, but from a systems biology perspective, CRP measurement is significant for understanding inflammatory processes and the body\\'s response to therapeutic interventions.'},\n", + " 'background': \"Based on the context provided and general knowledge about C-reactive protein (CRP), I can summarize the following background information:\\n\\n1. **Biological Function**:\\n - CRP, or C-reactive protein, is a substance produced by the liver in response to inflammation. It is a member of the class of acute-phase proteins, which increase in concentration in response to inflammation. CRP is commonly measured in clinical settings as a marker of inflammation.\\n\\n2. **Role in Pathways**:\\n - CRP is part of the body's immune response and plays a role in recognizing pathogens and damaged cells, thereby promoting their clearance through interaction with the complement system and other immune pathways. The context involving IL-6 and anti–IL-6Rα antibody treatment suggests an interest in inflammatory pathways where CRP is a downstream marker of cytokine (like IL-6) activity.\\n\\n3. **Interactions with Other Molecules**:\\n - CRP interacts with phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) to activate the complement system. It is known that CRP levels are regulated by cytokines, particularly interleukin-6 (IL-6), which is relevant in the context of anti-IL-6 therapy described in the document.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n - The suppression and modulation of serum CRP levels are used as a measure to validate models simulating the effects of anti-IL-6Rα antibody therapy (such as with tocilizumab) in clinical settings. In this context, CRP (% of baseline) acts as a biomarker to assess the efficacy of treatment options targeting inflammatory pathways and the IL-6 signaling axis. It indicates the level of inflammation within patients undergoing such treatments.\\n\\nThe reference to CRP (% of baseline) reflects normalized data used to compare changes in serum CRP levels over time, particularly in response to medical interventions, such as administration of anti-inflammatory drugs. This emphasizes its utility as a reliable marker for evaluating treatment responses in clinical trials and models related to inflammatory diseases.\"},\n", " {'id': 'mw80848184_e2dd_47ce_86d7_7a21479342bd',\n", " 'name': 'gp130',\n", " 'original_name': 'gp130',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"The species named 'gp130' refers to a protein that plays a significant role in the signaling pathway involving interleukin-6 (IL-6) and its receptor. \\n\\n### Biological Function:\\n- **gp130 is a Signal Transducer**: It is primarily a signal-transducing component of the IL-6 receptor complex. It does not bind IL-6 by itself but acts as a signal transducer when associated with IL-6 and IL-6 receptor (IL-6R).\\n\\n### Role in Pathways:\\n- **Interaction with IL-6/IL-6R**: gp130 is crucial in the formation of the signaling complex with IL-6 and its soluble receptor sIL-6R. This complex is central to IL-6 signaling pathways.\\n- **Inhibition of IL-6 Trans-Signaling**: A fusion protein known as sgp130Fc, which combines the extracellular portion of gp130 with an Fc region, has been shown to inhibit IL-6 trans-signaling, demonstrating gp130’s role in regulatory mechanisms.\\n\\n### Interactions with Other Molecules:\\n- **Complex Formation**: It forms a complex with IL-6 and IL-6R, contributing to signal transduction.\\n- **Natural Inhibitor**: Soluble gp130 (sgp130) serves as a natural inhibitor of the IL-6/sIL-6R signaling pathway, preventing excessive signal transduction.\\n\\n### Importance in the Biological System:\\n- **Regulatory Role**: The high baseline level of soluble gp130 (sgp130) in the system acts as a buffering agent against changes in the levels of IL-6/sIL-6R complex, highlighting its regulatory importance.\\n- **Therapeutic Potential**: Therapeutic approaches using sgp130 to target IL-6 signaling pathways, such as in the treatment of Crohn’s disease, underscore its clinical significance.\\n \\nGiven these roles, gp130 is a critical component in the IL-6 signaling pathway and has potential therapeutic implications due to its regulatory capacities in controlling inflammatory responses.\"},\n", + " 'background': \"Based on the provided context, the biological species named 'gp130' appears to be a critical component in the interleukin-6 (IL-6) signaling pathway. Here's a summary of its role and importance:\\n\\n### Biological Function:\\n- **Gp130** serves as a signal-transducing coreceptor in the IL-6 signaling pathway.\\n- It acts as part of a complex with the IL-6 receptor (IL-6R) and is involved in mediating the downstream effects of IL-6.\\n\\n### Role in Pathways:\\n- **IL-6 Signaling**: Gp130 is a key component in the assembly of the IL-6/IL-6R/gp130 complex. This is crucial for the signaling cascade that drives various inflammatory and immune responses.\\n- **Inhibition of IL-6 Trans-Signaling**: The soluble form of gp130 (sgp130) can inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing its interaction with membrane-bound gp130 and subsequent signaling.\\n\\n### Interactions with Other Molecules:\\n- **IL-6 and IL-6R**: Gp130 interacts with IL-6 bound to its receptor IL-6R, forming a complex necessary for initiating signal transduction.\\n- **Soluble IL-6 Receptor (sIL-6R)**: It is noted that sgp130 is a natural inhibitor of the soluble IL-6 receptor, indicating a regulatory role in modulating the availability and activity of IL-6.\\n\\n### Importance in the Biological System:\\n- Gp130 is vital for the modulation of immune responses and inflammation through its role in IL-6 signaling.\\n- **Therapeutic Potential**: Its soluble form, sgp130, has been studied for therapeutic applications, including its potential use in diseases characterized by excessive IL-6 signaling, such as Crohn's disease. The context mentions simulations of sgp130Fc (a fusion protein of sgp130 with the Fc region of an antibody) for therapeutic dosing.\\n- **Baseline Levels**: The high baseline levels of sgp130 compared to IL-6 indicate its prominent regulatory role in the signaling environment.\\n\\nIn summary, gp130 is a crucial component of the IL-6 signaling pathway with significant implications in inflammation and immune modulation. Its interactions and regulatory capabilities make it a target for therapeutic intervention, especially in inflammatory diseases.\"},\n", " {'id': 'mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a',\n", " 'name': 'R_IL6_gp130',\n", " 'original_name': 'R_IL6_gp130',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"The species named 'R_IL6_gp130', based on its naming and the context provided, likely refers to a complex or interaction involving the cytokine interleukin-6 (IL-6) and the signal transducer glycoprotein 130 (gp130). While the specific document does not provide detailed information about R_IL6_gp130, general knowledge about the IL-6/gp130 interaction helps us understand its potential biological significance.\\n\\n### Biological Function:\\n- **IL-6:** It is a cytokine involved in the regulation of immune responses, inflammation, and hematopoiesis. It plays a crucial role in acute phase responses and is produced at sites of inflammation.\\n- **gp130:** It serves as a signal transducer in the cytokine receptor complex, particularly for the IL-6 family of cytokines. It is involved in several cellular processes, including cell growth and differentiation.\\n\\n### Role in Pathways:\\n- The IL-6/gp130 interaction is central to both classical and trans-signaling pathways. In classical signaling, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), which then associates with gp130 to initiate downstream signaling.\\n- In trans-signaling, IL-6 binds to a soluble form of the IL-6 receptor (sIL-6R), and this complex can then associate with gp130 on the target cell surface, allowing cells that do not express membrane-bound IL-6R to respond to IL-6.\\n\\n### Interactions with Other Molecules:\\n- gp130 is a common subunit shared by several cytokine receptors in the IL-6 family, meaning it participates in a variety of signaling complexes.\\n- The soluble form of gp130 (sgp130) can act as a natural inhibitor by binding to IL-6/sIL-6R complexes and preventing them from interacting with membrane-bound gp130.\\n\\n### Importance in the Biological System Being Modeled:\\n- Given the context of inflammatory diseases such as Crohn’s disease, the IL-6/gp130 axis is likely a critical component in the inflammatory response modulation.\\n- The application of sgp130, or its fusion forms like sgp130Fc, demonstrates the pathway's therapeutic significance as a target for damping excessive IL-6-mediated signaling in inflammatory diseases.\\n\\nIn summary, R_IL6_gp130 refers to a key interaction in the IL-6 signaling pathway, emphasizing its role in inflammatory responses and its potential as a therapeutic target in autoimmune diseases like Crohn's.\"},\n", + " 'background': \"Based on the context and general knowledge about similar biological components, the species 'R_IL6_gp130' likely refers to a complex involving interleukin-6 (IL-6), its receptor (IL-6R), and the signaling component gp130. Here's a summary of what is generally known about the components involved:\\n\\n1. **Biological Function:**\\n - Interleukin-6 (IL-6) is a cytokine involved in immune responses, inflammation, and hematopoiesis. It mediates its effects through the IL-6 receptor (IL-6R) and the signal transducer gp130.\\n - gp130 is a transmembrane protein that, upon IL-6 binding to IL-6R, forms a complex through which signal transduction occurs, initiating intracellular signaling cascades primarily involving the JAK-STAT pathway.\\n\\n2. **Role in Pathways:**\\n - The IL-6/IL-6R/gp130 signaling complex plays a crucial role in the JAK-STAT signaling pathway. This pathway is pivotal in promoting gene expression associated with inflammatory responses.\\n - The pathway can occur through classical signaling, where IL-6 binds to its membrane-bound receptor IL-6R, or through trans-signaling, where IL-6 binds to a soluble form of IL-6R (sIL-6R), interacting with membrane-bound gp130 in cells that do not express IL-6R.\\n\\n3. **Interactions with Other Molecules:**\\n - IL-6 binding to IL-6R and subsequent interaction with gp130 triggers gp130 dimerization and activation of associated JAK kinases, leading to phosphorylation and activation of STAT3, a transcription factor.\\n - Soluble gp130 (sgp130) can inhibit IL-6-mediated trans-signaling by binding to the IL-6/sIL-6R complex, preventing it from interacting with membrane-bound gp130. This natural inhibitor is significant as it selectively inhibits the trans-signaling pathway.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - The IL-6/gp130 signaling axis is critical in inflammatory diseases, including Crohn's disease and other autoimmune conditions. The document highlights the therapeutic potential of modulating this pathway, particularly using sgp130Fc (a fusion protein analog of gp130) to inhibit IL-6 trans-signaling.\\n - Pharmacokinetic (PK) studies and simulations of sgp130Fc are mentioned, indicating its evaluation as a therapeutic intervention targeting this pathway, aiming to reduce inflammation markers like CRP (C-reactive protein) and pSTAT3 in the gut.\\n\\nIn summary, 'R_IL6_gp130' likely represents a signaling complex crucial for mediating inflammatory responses in various biological settings, making it a significant therapeutic target, especially in inflammatory and autoimmune diseases.\"},\n", " {'id': 'mw4638f126_8cb8_4021_ab41_6ae195743ba0',\n", " 'name': 'sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", " 'original_name': 'sR_IL6',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"Based on the provided context and general knowledge, here is the background information on the species 'sR_IL6' with the identifier 'mw4638f126_8cb8_4021_ab41_6ae195743ba0', situated within 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e':\\n\\n1. **Biological Function**: 'sR_IL6' likely refers to the soluble receptor for Interleukin-6 (sIL-6R). Soluble receptors such as sIL-6R can bind to the cytokine IL-6, acting as a co-receptor that allows IL-6 to engage in signaling pathways even in cells that do not express the membrane-bound IL-6 receptor.\\n\\n2. **Role in Pathways**: In the immune system, IL-6 can signal through two main pathways:\\n - **Classical signaling**: IL-6 binds to membrane-bound IL-6R and recruits the gp130 protein to initiate downstream signaling.\\n - **Trans-signaling**: sIL-6R, in complex with IL-6, engages gp130 on cells that do not have the IL-6 receptor, thus expanding the range of cells that can respond to IL-6. This is particularly relevant in inflammatory responses and is studied in contexts such as Crohn's disease.\\n\\n3. **Interactions with Other Molecules**: \\n - sIL-6R forms a complex with IL-6 which can then bind to gp130, leading to activation of downstream signaling pathways such as the JAK/STAT pathway.\\n - sIL-6R can be sequestered by sgp130, a soluble form of gp130, which can regulate the availability of the IL-6/sIL-6R complex for signaling.\\n - C-reactive protein (CRP) is involved in the production of sIL-6R through a process known as CRP-mediated shedding.\\n\\n4. **Importance in the Biological System**: \\n - sIL-6R plays a crucial role in mediating IL-6 trans-signaling, particularly in contexts like chronic inflammation and autoimmune diseases such as Crohn's disease.\\n - The presence of sIL-6R enables IL-6 to exert its effects even in cells lacking direct IL-6 receptors, thereby widening its scope of action within the immune regulatory processes.\\n - Understanding the dynamics of sIL-6R in combination with IL-6 is important for therapeutic considerations, as targeting these complexes can influence pharmacological outcomes in disease states.\\n\\nThus, sR_IL6 (inferred as sIL-6R) is integral to the IL-6 signaling pathways, facilitating broad immunological responses through its role in trans-signaling and interaction with IL-6 and other molecular regulators like sgp130.\"},\n", + " 'background': 'The molecule in question, sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2), can be inferred to relate closely to soluble IL-6 receptor components based on its name and ID positioning within a model of IL-6 signaling. Although there is no explicit information about this exact species in the provided context, some relevant points about similar molecules can be derived.\\n\\n### **Biological Function:**\\n- **sIL-6R (soluble IL-6 receptor)**: Typically, sIL-6R refers to a soluble form of the IL-6 receptor, which allows IL-6 to transduce signals through cells that do not express the membrane-bound IL-6 receptor. This process is part of what is known as IL-6 trans-signaling. In the context of the model being described, sR_IL6 may play a similar role.\\n\\n### **Role in Pathways:**\\n- **IL-6 Signaling**: It functions within the IL-6 signaling pathway, which can occur via classical signaling or trans-signaling. Classical signaling involves membrane-bound IL-6R and gp130, while trans-signaling involves sIL-6R.\\n- **Interaction with sgp130**: The sIL-6R/IL-6 complex can be sequestered by another molecule, sgp130, preventing further signaling.\\n\\n### **Interactions with Other Molecules:**\\n- **IL-6/sIL-6R Complex**: It forms a complex with IL-6, which can engage with gp130 on cell membranes, activating downstream signaling cascades.\\n- **CRP Influence**: The production of sIL-6R is influenced by CRP (C-reactive protein), which mediates its shedding.\\n\\n### **Importance in the Biological System Being Modeled:**\\n- **Crohn’s Disease**: The IL-6/sIL-6Rα complex plays a significant role in the context of Crohn’s disease, a chronic inflammatory condition. Therapeutic strategies targeting this complex have been simulated to evaluate their effects on disease dynamics.\\n- **Pharmacological Efficacy**: In therapeutic models, blocking the IL-6/sIL-6Rα complex alongside free IL-6 has been shown to improve pharmacological efficacy, implying its critical role in modulating immune responses.\\n\\nIn summary, sR_IL6 is likely involved in facilitating trans-signaling in IL-6 pathways, interacting with other components like IL-6, gp130, and CRP, with implications for inflammatory diseases such as Crohn’s disease. These inferred roles suggest its significance in the physiological and pathological contexts of IL-6 mediated immune regulation.'},\n", " {'id': 'mw10315fa3_6f13_4618_bda8_a8694bd3c374',\n", " 'name': 'R',\n", " 'original_name': 'R',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"Given the context provided, the information about the species named 'R' (ID: mw10315fa3_6f13_4618_bda8_a8694bd3c374) is not directly mentioned in the documents. However, we can make inferences based on the information about related molecules and pathways described in the context, particularly those involving IL-6 (interleukin-6) and its receptor.\\n\\n### Inferred Background Information about 'R':\\n\\n1. **Biological Function**:\\n - Since the context discusses IL-6 and its receptors (sIL-6R and IL-6Rα), 'R' could potentially be related to components in the IL-6 signaling pathway. IL-6 is a cytokine involved in inflammation and immune response regulation.\\n\\n2. **Role in Pathways**:\\n - IL-6 interacts with both membrane-bound and soluble forms of its receptor (IL-6R) to initiate downstream signaling cascades, such as the JAK/STAT pathway, which leads to the activation of transcription factors like STAT3 (signal transducer and activator of transcription 3).\\n - The pathway is involved in the transcription of various genes, including those coding for acute-phase proteins like CRP (C-reactive protein), indicating a role in inflammatory processes and liver function.\\n\\n3. **Interactions with Other Molecules**:\\n - IL-6, in combination with its receptor, can activate a signaling complex that involves the JAK proteins and STAT3, influencing gene expression. Soluble forms of the receptor, such as sIL-6R, play a role in trans-signaling, which can modulate responses in cells that do not express the membrane-bound receptor.\\n\\n4. **Importance in the Biological System**:\\n - Given that IL-6 signaling impacts acute-phase response and immune regulation, molecules within this pathway, including 'R' if it is part of this system, are crucial for modulating inflammatory responses. They may be targeted in therapeutic contexts, such as with anti–IL-6 or anti–IL-6Rα therapies, which are indicated in the documents as treatments influencing biomarkers like CRP.\\n\\nIn conclusion, without specific data directly linked to 'R', it can be inferred that 'R' is potentially part of the IL-6 pathway components, involved in immune and inflammatory responses, and plays a significant role in cellular signaling and communication within this biological system.\"},\n", + " 'background': \"The provided context refers to interactions and functions related to the interleukin-6 receptor (IL-6R), yet there is no explicit mention of a species or molecule specifically called 'R'. However, we can infer that 'R' might refer to the interleukin-6 receptor (IL-6R) or components associated with it based on the context of the documents provided. Here's a summary of relevant information that could be applicable to 'R', especially if it is related to IL-6R:\\n\\n1. **Biological Function**:\\n - The IL-6 receptor (IL-6R) plays a critical role in the immune response. It is involved in the signaling pathway for interleukin-6 (IL-6), a cytokine that influences immune regulation, inflammation, and hematopoiesis.\\n\\n2. **Role in Pathways**:\\n - IL-6R is a part of the Classical and Trans signaling pathways. In the Classical pathway, it binds IL-6, leading to dimerization with gp130 and activation of the JAK/STAT signaling cascade, particularly resulting in the phosphorylation and activation of STAT3. This pathway has significant implications for transcriptional regulation of various genes.\\n - The IL-6 trans-signaling involves soluble IL-6R (sIL-6R) and affects cells that do not naturally express IL-6R on their surface, further enabling broader physiological effects.\\n \\n3. **Interactions with Other Molecules**:\\n - IL-6R interacts with IL-6 and gp130 in both the Classical and Trans signaling pathways.\\n - Antibodies targeting IL-6R, such as those mentioned in the context (e.g., anti–IL-6Rα antibodies), are used to modulate its function, particularly as therapeutic interventions to reduce inflammation or lower C-reactive protein (CRP) levels.\\n\\n4. **Importance in the Biological System**:\\n - In the context of disease and therapy, IL-6R is a target for modulating inflammatory responses, as its activation leads to increased levels of acute-phase proteins such as CRP, which are markers for inflammation.\\n - The modulation of IL-6R, such as through the use of antibodies, is significant in clinical settings for managing conditions characterized by excessive inflammation or immune activation.\\n\\nBased on the described interactions and importance, if 'R' refers to the IL-6 receptor or a similar component, it acts as a central mediator in inflammatory pathways and is a critical target for therapeutic interventions.\"},\n", " {'id': 'mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1',\n", " 'name': 'IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", " 'original_name': 'IL6',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"Based on the context provided, the species referred to as 'IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is likely Interleukin-6 (IL-6), a cytokine involved in various biological processes. Here is a summary of relevant background information about IL-6:\\n\\n1. **Biological Function:**\\n - IL-6 is a cytokine that plays a crucial role in immune regulation. It is involved in the inflammatory response and is essential for the body's defense against infections and injuries.\\n\\n2. **Role in Pathways:**\\n - IL-6 signaling can occur through two main pathways:\\n - **Classical Pathway:** This involves the membrane-bound IL-6 receptor (IL-6Rα) where IL-6 binds to IL-6Rα, forming a complex that recruits a membrane-bound gp130 coreceptor, triggering downstream signaling cascades.\\n - **Trans-signaling Pathway:** This involves the soluble IL-6 receptor (sIL-6Rα). The IL-6/sIL-6Rα complex can associate with gp130 to initiate signaling in cells that do not express the membrane-bound IL-6Rα. This pathway is particularly important in inflammatory diseases.\\n\\n3. **Interactions with Other Molecules:**\\n - IL-6 interacts with IL-6Rα and gp130 to form a receptor complex that activates intracellular signaling pathways.\\n - It leads to the phosphorylation of Janus kinase (Jak) family proteins and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3), which are critical for transmitting the signal inside the cell.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - In the context of Crohn's disease, IL-6 contributes to enhanced T-cell survival and resistance to apoptosis in the lamina propria, along with elevated chemokine secretion. This makes it a significant player in the disease's pathology.\\n - The study of IL-6 and its pathways is crucial in understanding its role in diseases such as Crohn's disease and rheumatoid arthritis, and in developing therapeutic interventions targeting IL-6 signaling.\\n\\nOverall, IL-6 is an important cytokine with significant roles in immune response and inflammation, making it a key target for research in immune-mediated diseases.\"},\n", + " 'background': \"Based on the context provided and general knowledge about IL-6, here is a summary of the information regarding IL-6, particularly in the context of immune regulation and diseases like Crohn's disease:\\n\\n1. **Biological Function**: IL-6 is a cytokine that plays a critical role in the immune system. It is involved in the regulation of immune responses, inflammation, and hematopoiesis. IL-6 is an important mediator in the body's response to infections and tissue injuries, helping to stimulate immune response.\\n\\n2. **Role in Pathways**: IL-6 signaling occurs via two main pathways:\\n - The classical pathway, mediated by the membrane-bound IL-6 receptor (IL-6Rα), which interacts with IL-6 to initiate signaling.\\n - The trans-signaling pathway, which involves the soluble IL-6 receptor (sIL-6Rα). In this pathway, the IL-6/sIL-6Rα complex can bind to the gp130 membrane-bound receptor to form an active signaling complex that initiates further downstream effects, such as the activation of Janus kinase (Jak) family proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation.\\n\\n3. **Interactions with Other Molecules**: IL-6 interacts with both its membrane-bound and soluble receptors (IL-6Rα and sIL-6Rα) to form complexes that recruit gp130, leading to signal transduction. The interaction with gp130 is crucial as it leads to the formation of an active hexameric receptor complex which drives further signaling processes.\\n\\n4. **Importance in Biological Systems**: IL-6 is particularly significant in the pathology of inflammatory diseases, such as Crohn's disease. It contributes to enhanced T-cell survival and apoptosis resistance, as well as elevated chemokine secretion in the intestinal mucosa and peripheral blood. This makes IL-6 signaling a critical target for therapeutic interventions in such conditions.\\n\\nIn summary, IL-6 is a multifunctional cytokine with essential roles in immune regulation and inflammatory responses, especially relevant to conditions like Crohn’s disease. Its ability to signal through multiple pathways and interact with various molecular complexes underscores its importance in maintaining immune homeostasis and its potential as a therapeutic target.\"},\n", " {'id': 'mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83',\n", " 'name': 'R_IL6',\n", " 'original_name': 'R_IL6',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"Based on the context provided, there is no specific mention of a species named 'R_IL6'. However, based on the context and related molecules mentioned, it is possible to infer some insights into what 'R_IL6' might relate to.\\n\\n### Biological Function:\\n- **IL-6:** IL-6 (Interleukin-6) is a cytokine involved in immune response, inflammation, and hematopoiesis. It plays a significant role in the body's defense mechanisms and is implicated in various diseases when dysregulated.\\n\\n### Role in Pathways:\\n- **IL-6 Signaling Pathway:** This pathway involves the binding of IL-6 to its receptor, IL-6R, and generally leads to the activation of JAK/STAT signaling pathways. This signaling can induce transcription and various immune responses.\\n\\n### Interactions with Other Molecules:\\n- **IL-6R and sIL-6R (soluble IL-6 receptor):** The IL-6 signaling requires the complex formation of IL-6 with its receptor IL-6R, including its soluble form sIL-6R. This complex can further bind to another molecule, gp130 (glycoprotein 130), which is necessary for signal transduction.\\n- **STAT3:** The context mentions pSTAT3 signaling, indicating that IL-6 signaling involves phosphorylation of STAT3, a transcription factor that mediates various gene expressions in response to IL-6.\\n\\n### Importance in the Biological System Being Modeled:\\n- **Regulation and Modeling:** IL-6 is involved in the regulation of immune processes, and its signaling is crucial in understanding conditions like Crohn's disease or rheumatoid arthritis. The context mentions modeling efforts and pharmacokinetic analyses suggesting a focus on IL-6 and its receptor interactions.\\n- **Treatment Implications:** The modeling discussed, such as the dose-response characteristics, indicates IL-6's importance in therapeutic frameworks, potentially focusing on disorders with immune dysregulation.\\n\\n### Potential Inference for 'R_IL6':\\n- While there is no direct mention of 'R_IL6', it could potentially refer to a variant, receptor, or complex of IL-6 involved in signaling pathways. It might be modeled similarly in studies related to immune regulation or therapeutic targeting. Given the context, it is likely associated with IL-6's complex pathways and interactions within the immune system.\\n\\nIn summary, 'R_IL6' could be a component related to IL-6 signaling, likely significant in immune system modeling and therapeutic interventions.\"},\n", + " 'background': 'The provided context does not explicitly detail the species \\'R_IL6\\' with the specified ID. However, based on the information present and general biological knowledge, \\'R_IL6\\' could potentially represent a receptor or related component involved in the Interleukin-6 (IL-6) signaling pathway.\\n\\n### General Knowledge Inference for \\'R_IL6\\':\\n1. **Biological Function**: \\n - IL-6 is a cytokine that plays a critical role in immune response, inflammation, and hematopoiesis. It typically signals through a receptor complex that may include the IL-6 receptor (IL-6R) and a signal transducer such as gp130.\\n - The designation \\'R_IL6\\' suggests it may be an IL-6 receptor component, involved in binding IL-6 and initiating downstream signaling pathways.\\n\\n2. **Role in Pathways**:\\n - IL-6 signaling involves the activation of the Janus kinase (Jak) and Signal Transducer and Activator of Transcription 3 (STAT3) pathway. Binding of IL-6 to its receptor complex activates these pathways, leading to the transcription of genes involved in inflammatory and immune responses.\\n - The context also mentions \"Classical\" and \"Trans\" pathways, suggesting classical signaling involves membrane-bound IL-6R, while trans-signaling involves soluble IL-6R (sIL-6R).\\n\\n3. **Interactions with Other Molecules**:\\n - IL-6 interacts with both its membrane-bound and soluble forms of IL-6R, which facilitates different signaling outcomes.\\n - Interaction with sIL-6R allows IL-6 to signal in cells that do not express membrane-bound IL-6R by associating with the ubiquitously expressed signal transducer, gp130.\\n - The term \\'R_IL6\\' within a complex might specifically denote its interaction with these molecules in such pathways.\\n\\n4. **Importance in the Biological System**:\\n - IL-6 signaling is crucial for immune regulation and has been implicated in several inflammatory diseases such as Crohn’s disease and rheumatoid arthritis.\\n - Modulating IL-6 activity, often through its receptor interactions, is a therapeutic target for reducing chronic inflammation and autoimmune diseases.\\n\\nOverall, while the specific role of \\'R_IL6\\' is not detailed in the provided text, understanding its potential place within IL-6 signaling pathways offers insights into its biological significance and therapeutic relevance.'},\n", " {'id': 'mw0eb6c959_d408_45a0_a450_928b8c5876bb',\n", " 'name': 'Ractive',\n", " 'original_name': 'Ractive',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"The context provided does not include specific information about a species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). However, I can provide inferential information based on the general context described, which involves IL-6 signaling and therapeutic interventions in conditions like rheumatoid arthritis and Crohn’s disease.\\n\\n1. **Biological Function:**\\n - Although 'Ractive' is not directly mentioned, within the context of an immune regulation framework, it could be hypothesized that 'Ractive' might represent a molecule involved in the immune response or signal transduction, perhaps similar to interleukins or receptors.\\n\\n2. **Role in Pathways:**\\n - Considering the IL-6 signaling pathway is a focal point of the study, 'Ractive' might play a role similar to elements of the IL-6 signaling cascade. This could involve participation in cytokine signaling or acting as a receptor or receptor complex, similar to IL-6 or its soluble receptor counterparts.\\n\\n3. **Interactions with Other Molecules:**\\n - 'Ractive' might engage in interactions akin to the IL-6 and its soluble receptor interactions. Such molecules often form complexes that could be potential targets for therapeutic antibodies or other modulators, a common approach in autoimmune conditions like those discussed.\\n\\n4. **Importance in the Biological System:**\\n - If 'Ractive' partakes in a pathway analogous to IL-6 signaling, it could be crucial in mediating inflammatory responses, playing a part in disease progression or resolution, and thus presenting itself as a possible target for therapeutic intervention.\\n\\nWithout specific information on 'Ractive' from the text, these interpretations are speculative and should be considered within the broader context of known signaling pathways and therapeutic targets discussed in the study.\"},\n", + " 'background': \"The provided context does not contain specific information about the species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). The text focuses primarily on the IL-6 signaling pathway, its associated components, and the effects of targeting this pathway with therapeutic antibodies such as anti-IL-6 and anti-IL-6Rα, particularly in the context of autoimmune diseases like Crohn's Disease and rheumatoid arthritis.\\n\\nSince there is no direct mention of 'Ractive' in the context, we can infer its nature based on the general themes discussed:\\n\\n1. **Biological Function & Role in Pathways**: Given the context's focus on the IL-6 pathway, Ractive might be hypothesized as a molecule related to cytokine signaling, possibly a receptor, a part of a signaling cascade, or even an associated regulatory protein modulating immune responses.\\n\\n2. **Interactions with Other Molecules**: In a systems biology model of immune regulation, Ractive might interact with cytokines (like IL-6), receptors (such as IL-6Rα), or downstream signaling molecules (e.g., STAT proteins). Its interactions would be crucial for understanding the dynamics of the immune response.\\n\\n3. **Importance in the Biological System**: If Ractive is indeed involved in the IL-6 mediated pathway, it would be important for modulating immune responses, potentially influencing inflammation and immune system activity, which are critical in conditions like Crohn’s Disease.\\n\\nIn the absence of context-specific information about 'Ractive', it is important to consult the original source documents or related scientific literature for precise insights into this species’ characteristics and role within the biological system being modeled.\"},\n", " {'id': 'mw42054cd7_17af_46da_970c_7f99151906ad',\n", " 'name': 'STAT3',\n", " 'original_name': 'STAT3',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"Based on the provided context and general knowledge:\\n\\n### Biological Function of STAT3\\nSTAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor activated by phosphorylation. It is a key player in transmitting signals from various cytokines and growth factors to the cell nucleus, where it modifies gene expression. STAT3 is critical for regulating numerous biological processes, including cell growth, apoptosis, and immune response.\\n\\n### Role in Pathways\\nSTAT3 is involved in the JAK-STAT signaling pathway. Upon activation, typically by cytokines such as IL-6, STAT3 is phosphorylated by associated Janus kinases (JAKs), dimerizes, and translocates to the nucleus. In this context, STAT3 appears integral to the IL-6 signaling pathway, which is involved in various cellular responses, including inflammation, immune function, and acute-phase reactions.\\n\\n### Interactions with Other Molecules\\nWithin the IL-6 signaling pathway, STAT3 interacts with molecules such as the IL-6 receptor (IL-6R), gp130, and soluble forms of these receptors (sIL-6R and sgp130). The phosphorylation of STAT3 (pSTAT3) indicates its activation and subsequent transcriptional regulation of target genes.\\n\\n### Importance in Biological Systems\\nSTAT3 plays a significant role in mediating the effects of cytokines like IL-6, which are crucial in immune responses and inflammation. The context mentions disease models such as Crohn's disease, where increased activation of STAT3 (pSTAT3) in tissues is noted, highlighting its potential role in the disease's inflammatory processes. This suggests that STAT3's regulation is pivotal in understanding and developing therapeutic approaches for immune and inflammatory disorders.\\n\\nIn summary, STAT3 is a central molecule in cytokine signaling pathways that influence immune function and inflammation, making it a critical target for studying diseases characterized by dysregulated immune responses, such as Crohn's disease.\"},\n", + " 'background': \"Based on the provided context and general knowledge, here is the background information about STAT3:\\n\\n### General Background on STAT3:\\nSTAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that is pivotal in transmitting signals from the cell surface to the nucleus. It is part of the STAT protein family and is involved in cellular processes such as cell growth and apoptosis.\\n\\n### Biological Function:\\nSTAT3 is primarily activated through phosphorylation—a process in which a phosphate group is added, often leading to a functional change of the protein. Once phosphorylated (pSTAT3), it dimerizes and translocates to the nucleus where it can influence the expression of a variety of genes.\\n\\n### Role in Pathways:\\nSTAT3 is a critical component of the JAK-STAT signaling pathway, which is a chain of interactions between proteins in a cell, and is also involved in mediating responses to cytokines and growth factors. In this context, it appears specifically related to IL-6 signaling. IL-6 is a cytokine that can induce the phosphorylation of STAT3, leading to its activation and subsequent gene transcription that drives processes like differentiation of lymphocytes and expression of acute-phase proteins such as C-reactive protein (CRP).\\n\\n### Interactions with Other Molecules:\\nSTAT3 interacts with various molecules primarily through the phosphorylation process. It is closely tied to components like gp130 and sIL-6R in the IL-6 signaling cascade. In response to IL-6, the receptor complex that includes IL-6Rα and gp130 becomes activated, leading to JAK activation and subsequent phosphorylation of STAT3.\\n\\n### Importance in Biological Model:\\nWithin the context of the provided information, STAT3 plays a significant role in diseases such as Crohn's disease, where its phosphorylated form, pSTAT3, has been observed in colon biopsies. This suggests that STAT3 might be central to inflammatory signaling pathways that underpin certain diseases, making it a potential target for therapeutic interventions.\\n\\nThis inferred understanding aligns with its general role in bodily immunity and inflammation, highlighting its potential implications in both research and clinical settings relevant to cytokine signaling and immune response regulation.\"},\n", " {'id': 'mw39c2e431_fdc3_4964_be29_6ca856620b1b',\n", " 'name': 'pSTAT3',\n", " 'original_name': 'pSTAT3',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': 'The context provided mainly revolves around the IL-6 signaling pathway and its components, such as IL-6Rα, gp130, sIL-6Rα, sgp130, and CRP, with sporadic mentions of STAT3 and pSTAT3. Here’s a summary focused on pSTAT3 based on the document and broader biological knowledge:\\n\\n### pSTAT3 Biological Function\\n- **pSTAT3** refers to the phosphorylated form of STAT3 (Signal Transducer and Activator of Transcription 3).\\n- STAT3 is a transcription factor activated in response to cytokines like IL-6.\\n- When phosphorylated, STAT3 dimerizes and translocates to the nucleus to regulate the expression of target genes.\\n\\n### Role in Pathways\\n- **IL-6 Signaling**: pSTAT3 is a critical component of the IL-6 signaling pathway. The binding of IL-6 to its receptor leads to the activation of the JAK kinases, which in turn phosphorylate STAT3.\\n- **Gene Expression**: pSTAT3 influences the transcription of various genes involved in immune responses, cell survival, and proliferation.\\n\\n### Interactions with Other Molecules\\n- **IL-6 and sIL-6Rα**: The context describes the significance of trans-signaling mediated by IL-6 and its soluble receptor forms, which lead to STAT3 phosphorylation.\\n- **gp130**: This coreceptor is crucial for the activation of STAT3. It binds the IL-6/sIL-6R complex leading to STAT3 phosphorylation.\\n- **CRP and other gene products**: The activation of STAT3 can influence the expression of C-reactive protein and other acute-phase proteins.\\n\\n### Importance in the Biological System\\n- **Pathological Conditions**: The document mentions increased pSTAT3 levels in colon biopsies in the context of Crohn’s disease, suggesting its role in inflammatory bowel diseases.\\n- **Biological Significance**: Being a part of the IL-6 signaling pathway, pSTAT3 is important in mediating immune responses and might have implications in various diseases due to dysregulated cytokine signaling.\\n\\nIn summary, pSTAT3 is a pivotal signaling molecule involved in transcriptional regulation, primarily within the IL-6-mediated pathway. Its phosphorylation status determines its activity, which can impact various biological processes and contributes to disease states such as inflammatory bowel disease.'},\n", + " 'background': \"Based on the provided context and general knowledge, here's an overview of pSTAT3:\\n\\n### Biological Function:\\n- pSTAT3, or phosphorylated STAT3, is part of the STAT (Signal Transducer and Activator of Transcription) family of transcription factors. These proteins are crucial for relaying information from extracellular signals to the cell nucleus, where they influence gene expression.\\n- Upon activation, STAT3 becomes phosphorylated, hence pSTAT3, which allows it to dimerize (pair with another STAT3 molecule), translocate to the nucleus, and bind to DNA, promoting the transcription of target genes.\\n\\n### Role in Pathways:\\n- pSTAT3 is instrumental in the IL-6 signaling pathway. IL-6 is a cytokine that, upon binding to its receptors, activates the Janus kinase (Jak) pathway, which in turn phosphorylates STAT3.\\n- The context describes a trans-signaling pathway involving IL-6 and its soluble receptor sIL-6Rα, with pSTAT3 being a downstream effector of this pathway.\\n- This pathway is crucial for various cellular responses, including differentiation, survival, and proliferation, especially in immune and inflammatory responses.\\n\\n### Interactions with Other Molecules:\\n- The phosphorylation of STAT3 is a result of interactions with upstream kinases like Jak, following cytokine receptor activation (e.g., by IL-6/sIL-6Rα).\\n- pSTAT3 is known to interact with various co-factors and DNA sequences to regulate the expression of genes involved in inflammation and immune responses.\\n- It is hinted that pSTAT3 levels are elevated in inflammatory conditions like Crohn’s disease, indicating interactions with molecules or pathways involved in inflammation.\\n\\n### Importance in the Biological System:\\n- pSTAT3 is a critical mediator in the context of inflammatory diseases, such as Crohn’s disease, where its increased levels in colon biopsies suggest a role in the pathogenesis or progression of these diseases.\\n- By regulating gene expression in response to cytokine signaling, STAT3, especially in its phosphorylated form, is important for maintaining appropriate immune responses and cellular homeostasis.\\n- Its role extends beyond normal physiology to pathophysiological conditions, where its dysregulation is often linked to chronic inflammatory states, autoimmune disorders, and even cancers.\\n\\nIn summary, pSTAT3 is a pivotal molecule within the IL-6 cytokine signaling pathway, acting as a key transcriptional regulator in immune and inflammatory responses. Its heightened activity is associated with pathological conditions, highlighting its importance as a potential therapeutic target in such diseases.\"},\n", " {'id': 'mwd5313618_89eb_4c8c_bc82_66f10f966349',\n", " 'name': 'CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", " 'original_name': 'CRP',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': 'The species referred to as \"CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\" in the provided context likely represents C-reactive protein (CRP), based on the common abbreviation for C-reactive protein. Here is a summary of the relevant background information regarding CRP:\\n\\n1. **Biological Function:**\\n - CRP is an acute-phase protein produced by the liver in response to inflammation. Its primary function is to bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system via C1q.\\n\\n2. **Role in Pathways:**\\n - CRP is often used as a clinical biomarker for inflammation. It plays a significant role in the pathway of immune response, particularly in recognizing and promoting the clearance of pathogens and damaged cells, thereby serving as a marker of inflammation and immune system activation.\\n - In the context of the simulation model discussed, changes in CRP levels can indicate the effectiveness of drug treatments targeting the IL-6 signaling pathway, as CRP levels are a downstream effect of cytokine signaling, particularly IL-6.\\n\\n3. **Interactions with Other Molecules:**\\n - CRP interacts with various components of the immune system such as the complement system. It works closely with interleukin-6 (IL-6), as IL-6 is a major inducer of CRP synthesis in the liver.\\n - The context mentions interactions with drugs such as anti-IL-6Rα antibodies, which suggests that CRP levels are used to measure the impact of these treatments on inflammation levels in diseases like Crohn\\'s disease.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - Within the modeled system (as described in the context), CRP serves as a critical marker for inflammation, allowing researchers to predict the impact of various treatment strategies on inflammatory diseases like Crohn\\'s disease.\\n - The model’s ability to predict changes in CRP levels helps in studying the effects of perturbations through different therapeutic approaches aimed at inhibiting the IL-6 signaling pathway.\\n\\nOverall, CRP is an important indicator of inflammation and is crucial in the validation and assessment of disease models involving inflammatory processes, such as those involving IL-6 signaling.'},\n", + " 'background': \"Based on the context provided, here is the background information about the species 'CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)':\\n\\n1. **Biological Function**: CRP, or C-reactive protein, is a biomarker of inflammation in the body. It is produced by the liver in response to inflammation and its levels increase in the bloodstream during inflammatory processes.\\n\\n2. **Role in Pathways**: CRP is primarily associated with the body's immune response to inflammation. It is part of the acute phase response, which is a rapid systemic response to injury, infection, or other inflammatory stimuli. The context suggests that CRP is being used in a model to evaluate inflammation levels, particularly in relation to Crohn’s disease and the effects of anti-inflammatory drugs like tocilizumab.\\n\\n3. **Interactions with Other Molecules**: CRP interacts with various components of the immune system. In the context of the document, CRP levels are used to assess the effectiveness of inhibiting IL-6 signaling—a cytokine involved in inflammation by targeting IL-6 or its receptors. Thus, CRP serves as an indicator for the efficacy of this anti-inflammatory strategy.\\n\\n4. **Importance in the Biological System Being Modeled**: In the model described, CRP is a critical marker used to validate and predict the outcomes of drug treatments aimed at reducing inflammation, such as those used in Crohn's disease. The model uses CRP as a metric to evaluate the suppression of inflammation due to the therapeutic inhibition of IL-6 signaling pathways.\\n\\nIn summary, CRP is an important inflammatory marker used in the modeling of immune response and drug efficacy in inflammatory diseases, particularly for evaluating interventions targeting IL-6 signaling.\"},\n", " {'id': 'mw2e464cf3_a09c_4b7c_9f3c_06720016a48e',\n", " 'name': 'sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", " 'original_name': 'sR',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"Based on the provided context, specific information about the species 'sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned. However, inferring from the general context of the documents, which involve molecular interactions and pathways related to the IL-6 signaling system, the following insights can be suggested:\\n\\n1. **Biological Function**:\\n - The 'sR' component is likely a part of the IL-6 signaling pathway. In similar contexts, 'sR' often denotes soluble receptors. Soluble receptors can modulate the activity of their respective cytokines or hormones by binding to them and altering their bioavailability or impacting downstream signaling pathways.\\n\\n2. **Role in Pathways**:\\n - Considering the IL-6 pathway is mentioned, the 'sR' species might function in the classical signaling or trans-signaling pathways of IL-6. In these pathways, soluble receptors either enhance or inhibit signal transduction, impacting gene expression mediated by factors like STAT3.\\n\\n3. **Interactions with Other Molecules**:\\n - The context suggests interaction with the IL-6 cytokine, as soluble IL-6 receptors (e.g., sIL-6R) bind IL-6, forming a complex (IL-6:sR) that may interact with other receptor components, such as gp130, to elicit a cellular response. These interactions are crucial for regulating inflammatory responses and immune function.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n - Soluble receptors are significant in maintaining homeostasis and regulating the intensity of cytokine signaling. The modeling aspect suggests that understanding the dynamic balance of these components (like sgp130, mentioned in the document) is crucial for accurately predicting system behavior under various conditions and treatments, especially targeting IL-6 or its receptors.\\n\\nIn summary, 'sR' in this context is likely a soluble receptor involved in the IL-6 signaling pathway, influencing immune responses by modulating cytokine availability and activity.\"},\n", + " 'background': \"From the context provided, it seems that the specific species 'sR' (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) is not directly mentioned or detailed. Thus, I will infer its possible role based on the general context involving related biological components.\\n\\n1. **Biological Function:**\\n - Given the surrounding context of interleukin 6 (IL-6), it is likely that 'sR' refers to a soluble receptor, potentially the soluble IL-6 receptor (sIL-6R). Soluble receptors often function to sequester ligands or modulate signaling pathways by facilitating ligand interaction with cell surface receptors.\\n\\n2. **Role in Pathways:**\\n - 'sR', if it represents sIL-6R, participates in the IL-6 signaling pathways. IL-6 can bind to sIL-6R, forming a complex that further associates with membrane-bound gp130, leading to activation of intracellular signaling pathways such as the JAK/STAT pathway. This pathway is involved in inflammation and the regulation of the immune response.\\n\\n3. **Interactions with Other Molecules:**\\n - 'sR' forms part of the IL-6/sIL-6R complex interacting with gp130, a common receptor subunit involved in IL-6 family cytokine signaling. This complex formation enhances signaling across various tissues, especially when the IL-6 concentration is limited, as seen from the content discussing IL-6 and sgp130 concentrations.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - If 'sR' represents a soluble receptor interacting with IL-6, it plays a crucial role in modulating IL-6's effects, potentially affecting processes like acute-phase responses, immune function, and inflammation. The model suggests that perturbations in components like sgp130 have minor effects due to concentration differences, implying that the effective modulation of signaling depends heavily on components like sR/sIL-6R and IL-6 interactions.\\n\\nIn summary, while 'sR' is not explicitly described, it might denote a molecule like the soluble IL-6 receptor within the context of IL-6 signaling pathways, influencing inflammatory and immune responses.\"},\n", " {'id': 'mw36ea78c1_ed71_4def_96d3_857a442d7195',\n", " 'name': 'CRPExtracellular',\n", " 'original_name': 'CRPExtracellular',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"The species named 'CRPExtracellular' likely refers to the extracellular form of C-reactive protein (CRP), a well-known biomarker and acute-phase protein in various biological systems, particularly in the context of inflammation.\\n\\n### Biological Function\\nC-reactive protein (CRP) is produced by the liver in response to inflammation. It is an acute-phase protein that plays a critical role in the host's defense mechanism. CRP is part of the innate immune system as it binds to the surface of dead or dying cells and certain bacteria to activate the complement system, promoting phagocytosis by macrophages.\\n\\n### Role in Pathways\\nIn the context of the provided documents, CRP is linked to the IL-6 signaling pathway. IL-6 is a cytokine that stimulates the production of CRP in the liver. The IL-6 mediated pathway contributes to inflammatory responses, and CRP serves as a downstream marker for inflammation. The model mentioned explores strategies to treat Crohn's disease by inhibiting IL-6 signaling, which suggests a modulation of CRP levels.\\n\\n### Interactions with Other Molecules\\nCRP interacts with various molecules and systems in the body:\\n- It binds to phosphocholine on the surface of dead cells and some types of bacteria.\\n- CRP activates the complement system, which enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells.\\n- CRP levels are used to assess the extent of inflammation in response to stimuli like IL-6, another cytokine involved in the body's inflammatory response.\\n\\n### Importance in the Biological System Being Modeled\\nIn the biological model presented in the documents, CRP serves as a critical biomarker to evaluate the efficacy of therapeutic strategies targeting IL-6 signaling in inflammatory diseases like Crohn's disease. The documents emphasize the model's capacity to predict the response of CRP levels to different treatment strategies, validating the trained model against clinical trial data. Suppression of CRP is an indicator of effective inhibition of inflammation, showcasing the importance of CRP measurement in assessing the success of interventions aimed at controlling inflammatory pathways.\\n\\nIn summary, CRPExtracellular represents the extracellular C-reactive protein operating as a biomarker for inflammation, influenced by IL-6 signaling pathways, and significant in evaluating treatment efficacy for diseases characterized by chronic inflammation.\"},\n", + " 'background': \"Based on the provided context, it seems that specific information about the species 'CRPExtracellular' (ID: mw36ea78c1_ed71_4def_96d3_857a442d7195) within the context of mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e is not explicitly detailed. However, we can infer some information based on the general role of C-reactive protein (CRP) within biological systems and its mention in the context.\\n\\n1. **Biological Function**: CRP, or C-reactive protein, is a substance produced by the liver in response to inflammation. Its primary function is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via the C1Q complex, thus playing an important role in the body's immune response by enhancing the ability to clear pathogens and damaged cells.\\n\\n2. **Role in Pathways**: CRP is typically involved in the acute phase response to inflammation. Its production increases in response to pro-inflammatory cytokines like interleukin-6 (IL-6), as indicated by the context mentioning IL-6 and CRP in relation to various treatments aiming to modulate inflammation pathways.\\n\\n3. **Interactions with Other Molecules**: The interaction between CRP and IL-6 is highlighted, with IL-6 being a key cytokine that stimulates the production of CRP. The context also discusses various treatment strategies that involve targeting IL-6 or its receptors to reduce inflammation and subsequently decrease CRP levels, demonstrating CRP's role as a marker for inflammatory activity and the effectiveness of anti-inflammatory treatments.\\n\\n4. **Importance in the Biological System Being Modeled**: The context suggests that CRP is used as a biomarker for inflammation in Crohn’s disease, and its levels are used to monitor the effectiveness of treatment strategies that target IL-6 signaling. Therefore, CRP is a key output in the model being discussed, representing the systemic inflammatory response and providing feedback on the effectiveness of therapeutic interventions.\\n\\nIn conclusion, while specific details about the species 'CRPExtracellular' in the mentioned context are not given, its role as a marker of inflammation and its regulation through pathways involving IL-6 are central to the model's focus on understanding and predicting the outcomes of therapeutic interventions in inflammatory conditions like Crohn’s disease.\"},\n", " {'id': 'mw147d30ec_478e_4090_b496_128a131d29eb',\n", " 'name': 'sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", " 'original_name': 'sgp130',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"The species referred to as 'sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' appears to be a protein known as sgp130 located in a specific biological context (ID: mw147d30ec_478e_4090_b496_128a131d29eb). Here is a summary of the relevant background information:\\n\\n1. **Biological Function**: \\n sgp130 is a soluble form of gp130, which is a component of the IL-6 receptor complex. sgp130 acts by binding to the IL-6/sIL-6Rα complex, thereby inhibiting IL-6 trans-signaling. This function is crucial as IL-6 trans-signaling is associated with various inflammatory and autoimmune conditions.\\n\\n2. **Role in Pathways**:\\n sgp130 plays a role in the IL-6 signaling pathway by inhibiting the formation of active signaling complexes. This modulation of the pathway can potentially reduce inflammatory responses mediated through IL-6 trans-signaling.\\n\\n3. **Interactions with Other Molecules**:\\n sgp130 interacts specifically with the complex formed by IL-6 and its soluble receptor sIL-6Rα. By binding to this complex, sgp130 prevents the subsequent interaction with the membrane-bound gp130, effectively blocking signal transduction.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n In the context of therapeutic applications, particularly for conditions such as Crohn's disease, sgp130 is evaluated for its potential use in inhibiting inflammatory signaling. Despite being present in large concentrations compared to IL-6, sensitivity analyses suggest that the therapeutic effectiveness of sgp130-based interventions may require very high doses due to its minimal impact on overall system dynamics at typical concentrations. This is because sgp130 naturally exists in excess relative to IL-6, limiting its impact when used in moderate amounts.\\n\\n5. **Relevance in Systems Biology Model**:\\n The systems biology model suggests that while sgp130 has a role, its overall impact on key output parameters (such as CRP levels) is limited unless used in substantial amounts. It highlights the need for potentially better therapeutic targets like IL-6 and sIL-6Rα, where alterations could more significantly affect system outputs.\\n\\nOverall, sgp130 serves a regulatory function in IL-6 mediated signaling, highlighting its role in inflammatory pathways but with suggested limitations for therapeutic application based on the systems biology model being considered.\"},\n", + " 'background': \"Based on the provided context, the species labeled as 'sgp130' (associated with ID: mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e) seems to be a fusion protein designed to interact with components involved in IL-6 signaling pathways. Here's a summary of its relevant aspects:\\n\\n- **Biological Function:**\\n - sgp130 functions as an inhibitor of IL-6 trans-signaling. It is a fusion protein that combines the extracellular portion of gp130 with the Fc region of human IgG1, termed sgp130Fc. This modification allows sgp130 to bind to the IL-6/sIL-6Rα complex.\\n\\n- **Role in Pathways:**\\n - It is involved in the IL-6 trans-signaling pathway. IL-6 is a cytokine that plays a crucial role in immune response and inflammation. The trans-signaling pathway involves the binding of IL-6 to a soluble receptor sIL-6Rα, which then associates with gp130 to signal.\\n\\n- **Interactions with Other Molecules:**\\n - sgp130 interacts specifically with the IL-6/sIL-6Rα complex. The context suggests that sgp130 binds this complex with similar affinity to natural gp130, aiming to inhibit downstream signaling events such as CRP (C-reactive protein) and pSTAT3 production in the gut.\\n\\n- **Importance in the Biological System:**\\n - Despite its designed purpose, simulations and sensitivity analyses indicate that sgp130 (as sgp130Fc) has relatively low impact on the biological system being modeled, particularly when used as a therapeutic agent for conditions like Crohn’s disease. Its effectiveness is noted only at very high and frequent doses due to the high baseline levels of sgp130 naturally present, in contrast to the low concentration of IL-6.\\n\\nIn summary, sgp130 is primarily modeled to inhibit IL-6 trans-signaling but poses challenges as a therapeutic due to its excess presence compared to IL-6, limiting its potential impact on the system without large dosage increases.\"},\n", " {'id': 'mwab41493c_6349_45f1_a226_3030cfed0e06',\n", " 'name': 'sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", " 'original_name': 'sR_IL6_sgp130',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"Based on the provided context, the species 'sR_IL6_sgp130', identified by the ID mwab41493c_6349_45f1_a226_3030cfed0e06, appears to be related to a fusion protein that plays a role in inhibiting IL-6 trans-signaling pathways. This fusion protein, popularly referred to as sgp130Fc, combines the extracellular portion of glycoprotein 130 (gp130) with the Fc region of human IgG1. \\n\\n**Biological Function:**\\nsR_IL6_sgp130 acts to bind specifically to the IL-6/sIL-6Rα complex, which is pivotal in mediating IL-6 trans-signaling. By binding to this complex, it effectively prevents the signaling process that would typically activate downstream pathways, such as the phosphorylation of STAT3 (pSTAT3) and subsequent gene transcription.\\n\\n**Role in Pathways:**\\nIts primary role resides in the inhibition of IL-6 trans-signaling, which is critical in the context of inflammatory responses and diseases like Crohn’s disease. The simulations and models cited suggest that this species is involved in modifying the dose-response relationship of certain therapeutic interventions, leading to outcomes like CRP suppression.\\n\\n**Interactions with Other Molecules:**\\nsR_IL6_sgp130 interacts predominantly with the IL-6/sIL-6Rα complex. The sgp130 component has a high affinity for this complex, which is a major interaction through which it achieves its inhibitory functions.\\n\\n**Importance in the Biological System Being Modeled:**\\nIn the system, while sR_IL6_sgp130 is present in high baseline levels and exerts limited effects on steady-state system dynamics due to its excess relative to free IL-6 concentrations, it remains a pivotal molecule for therapeutic applications. Its primary importance lies in its use as a potential therapeutic intervention, especially considered for conditions with elevated IL-6 trans-signaling, requiring very high and frequent doses to be effective due to its baseline levels.\\n\\nThis summary indicates that sR_IL6_sgp130 is critical in the context of therapies aiming to modulate IL-6 signaling pathways, providing insights into the need for precise dosing strategies to achieve therapeutic benefits.\"},\n", + " 'background': \"Based on the context provided, specific mentions of the species named 'sR_IL6_sgp130' (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) are not directly available. However, we can infer its nature and potential role based on the information about similar molecules provided in the document.\\n\\n1. **Biological Function**: The context discusses sgp130, which is known to be a soluble form of the gp130 receptor. These soluble receptors, like sgp130, are known to inhibit IL-6 trans-signaling. In general, soluble receptors can bind cytokines or cytokine complexes in the extracellular environment, preventing them from triggering cell surface receptors and subsequent intracellular signaling cascades.\\n\\n2. **Role in Pathways**: The sgp130 serves as an inhibitor in the IL-6 signaling pathway, particularly in IL-6 trans-signaling. This pathway is involved in various inflammatory and immune processes. By inhibiting this pathway, sgp130 could potentially reduce inflammatory responses, which is particularly relevant in conditions like Crohn’s disease, as mentioned in the context.\\n\\n3. **Interactions with Other Molecules**: The sgp130 binds to the IL-6/sIL-6Rα complex. This specific interaction is crucial for its role as an inhibitor in the pathway. It prevents the IL-6 complex from interacting with membrane-bound gp130, thus blocking downstream signaling events.\\n\\n4. **Importance in the Biological System Being Modeled**: In the biological system modeled, sgp130 appears to represent a regulatory component that modulates the IL-6 signaling pathway. Its presence in high baseline levels as compared to free IL-6 indicates a natural buffering or regulatory role in maintaining homeostasis in the signaling environment. It suggests that significant therapeutic modulation (e.g., large doses of sgp130Fc) would be needed to observe pronounced effects.\\n\\nWhile specific details about 'sR_IL6_sgp130' (#2) are not available, the understanding of sgp130's role in IL-6 trans-signaling and its functional characterization can be reasonably extrapolated to gain insights into this species' potential biological importance.\"},\n", " {'id': 'mwf405687b_7401_44ec_a0d6_4a2b35c13e8a',\n", " 'name': 'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", " 'original_name': 'Ab_sR',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': 'Based on the provided context, no specific information about the species named \\'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\\' was found in the excerpts from the document. However, I can infer some potential characteristics and roles it might have based on general biological knowledge and the information typically associated with similar components.\\n\\n1. **Biological Function**: Generally, \"Ab\" in a biological context often refers to antibodies. If \\'Ab_sR\\' is indeed an antibody or related to antibody activity, its function could be to bind to specific antigens, perhaps part of a signaling pathway or immune response mechanism.\\n\\n2. **Role in Pathways**: The context mentions IL-6 and its receptor interactions, which are part of immune signaling pathways. If \\'Ab_sR\\' is interacting with such pathways, it could be modulating or inhibiting specific signals, particularly in inflammatory or immune responses.\\n\\n3. **Interactions with Other Molecules**: As the context heavily references IL-6, IL-6R, and associated signaling components like STAT3 and SOCS, it is plausible that \\'Ab_sR\\' could interact with these molecules. It might bind to a receptor or signaling molecule to alter its activity.\\n\\n4. **Importance in the Biological System**: Assuming \\'Ab_sR\\' is an antibody related to receptor activity, it could be crucial in modulating inflammatory responses or other cytokine-related pathways. In systems biology models, such antibodies are often used to simulate therapeutic interventions, inhibiting specific pathways to predict changes in disease states or therapeutic outcomes.\\n\\nWithout explicit details from the document, these inferences remain general and speculative. Further details would be needed for precise characterization.'},\n", + " 'background': 'The context provided does not contain specific information about the biological species or molecule named \\'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)\\' or its ID \\'mwf405687b_7401_44ec_a0d6_4a2b35c13e8a\\'. Given the lack of direct details in the documents, I can infer potential characteristics of \\'Ab_sR\\' based on common biological concepts and patterns discussed in similar contexts.\\n\\n1. **Biological Function**: Given the use of \"Ab\" in the name, \\'Ab_sR\\' may refer to an antibody-related species, possibly a soluble receptor (sR) or an antibody-receptor complex. In many biological systems, antibodies play crucial roles in immune responses, binding to specific antigens to neutralize them or mark them for destruction by other immune cells.\\n\\n2. **Role in Pathways**: In the context of systems biology models that often study signaling and immune pathways, \\'Ab_sR\\' may be involved in modulating signaling cascades. Since the documents mention the IL-6/sIL-6Rα complex, \\'Ab_sR\\' might participate in pathways related to cytokine signaling, such as the interleukin-6 (IL-6) pathway, which is crucial in inflammation and immune regulation.\\n\\n3. **Interactions with Other Molecules**: Given the similarities to components like IL-6 and sIL-6Rα, \\'Ab_sR\\' may interact with these molecules either as a part of a complex or influence their activity. For instance, antibodies or their fragments (like those potentially represented by \\'Ab_sR\\') can bind to cytokines or their receptors, affecting the downstream signaling events.\\n\\n4. **Importance in the Biological System Being Modeled**: Systems biology models often explore the dynamics and regulation of complex biochemical networks. If \\'Ab_sR\\' is involved in cytokine-receptor interactions, it can be important in modulating inflammatory responses or immune system function, potentially making it a target for therapeutic interventions in diseases characterized by inflammation or immune dysfunction.\\n\\nTo summarize, while \\'Ab_sR\\' is not directly described in the context provided, it is likely associated with antibody or receptor functions within signaling or immune pathways similar to those of IL-6/sIL-6Rα in the documents referenced. If additional data is available, it could help refine or confirm these inferences.'},\n", " {'id': 'mw3667a5e1_02c9_44a0_acb4_b0431faa822d',\n", " 'name': 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", " 'original_name': 'Ab',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"Based on the context provided, there isn't directly available specific information about the species named 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, we can infer its role based on general knowledge and the content present in the documents.\\n\\n1. **Biological Function:** 'Ab' likely refers to an antibody, given the context of medical and pharmacological studies. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects, such as bacteria and viruses.\\n\\n2. **Role in Pathways:** Antibodies are a crucial part of the immune response, often engaging in pathways related to immune regulation and inflammatory responses. Specifically, within the context, it seems to be involved in pathways targeting IL-6 or IL-6Rα, which are significant in inflammatory processes and immune system signaling, especially in conditions like inflammatory bowel diseases and other inflammatory responses.\\n\\n3. **Interactions with Other Molecules:** Within the context, the antibodies interact with IL-6 and sIL-6Rα (soluble IL-6 receptor alpha). These interactions are essential as they form complexes that are targets for therapeutic interventions to suppress inflammatory markers like C-reactive protein (CRP). The effectiveness of such interventions can vary based on whether IL-6 and its receptor are targeted individually or together.\\n\\n4. **Importance in the Biological System:** Antibodies, like the one inferred (potentially anti-IL-6 or similar), are important in modulating the immune response and are used in therapeutic settings to treat diseases where cytokine activity (like that of IL-6) is dysregulated. They help reduce undesirable inflammation and are thus a critical part of managing inflammatory diseases.\\n\\nIn summary, while specific details about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' are not provided, it is most likely a therapeutic antibody involved in pathways targeting IL-6 and its receptor, pivotal in controlling inflammation within biological systems.\"},\n", + " 'background': \"The context provided does not offer any specific information about the species or molecule identified as 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' within the document. However, based on the excerpts, it is possible to infer the following general insights regarding similar biological components:\\n\\n1. **Biological Function**: The molecule labeled 'Ab' is likely an antibody, which are proteins used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. In this context, 'Ab' might refer to an antibody targeting a particular biological pathway or molecule.\\n\\n2. **Role in Pathways**: Antibodies are typically involved in immune response pathways. The document mentions interactions that involve the cytokine IL-6 and its receptor, IL-6Rα. It is possible that 'Ab' could be an antibody aimed at either IL-6 or IL-6Rα, or their complex, to modulate immune responses.\\n\\n3. **Interactions with Other Molecules**: The document excerpt references the targeting of IL-6 or its receptor, sIL-6Rα. These molecules play roles in inflammatory processes, indicating that 'Ab' might interact with these molecules and potentially be used to suppress inflammation or other immune responses.\\n\\n4. **Importance in the Biological System**: Antibodies like 'Ab' are important in a biological system because they can help to precisely modulate pathways that involve cytokines like IL-6, which are crucial in inflammatory and immune responses. This suggests its relevance in therapeutic interventions, especially in conditions where regulating immune activity is necessary.\\n\\nAn understanding of similar antibodies, like anti-IL-6 or anti-IL-6R antibodies, typically helps in reducing inflammation and is useful in treating conditions like rheumatoid arthritis and other autoimmune diseases.\\n\\nIn conclusion, while there is no direct information about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)', it can be inferred to be an antibody with potential functions related to immune modulation, likely within pathways involving IL-6 and its receptor(s).\"},\n", " {'id': 'mw772cbf20_3fc1_4800_ae59_77884f1ae333',\n", " 'name': 'Ab_R',\n", " 'original_name': 'Ab_R',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"The document provided does not explicitly mention the species 'Ab_R' with the ID 'mw772cbf20_3fc1_4800_ae59_77884f1ae333.' Therefore, I will infer what 'Ab_R' might pertain to based on the general knowledge presented in the context and common biological components.\\n\\n1. **Biological Function:**\\n - Given that the context mentions anti-IL-6 and anti-IL-6Rα antibodies, it is plausible that 'Ab_R' could represent an antibody (Ab) related to these immune system components. \\n\\n2. **Role in Pathways:**\\n - Antibodies targeting the IL-6/IL-6Rα pathway are involved in modulating inflammatory responses. IL-6 is a cytokine involved in immune regulation, and its receptor, IL-6Rα, can exist in both a soluble and membrane-bound form, playing roles in signaling cascades that promote inflammation.\\n\\n3. **Interactions with Other Molecules:**\\n - If 'Ab_R' is, in fact, an antibody similar to anti-IL-6 or anti-IL-6Rα, it would likely bind to these targets to inhibit cytokine signaling, thereby reducing inflammation. It may interact with IL-6, IL-6Rα, or both.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - The context of the document suggests a focus on modeling pharmacokinetics and pharmacodynamics (PK/PD) of antibodies targeting IL-6/IL-6Rα pathways, often to evaluate potential therapeutic interventions for conditions involving chronic inflammation, such as autoimmune diseases or inflammatory diseases like Crohn’s disease (CD).\\n - Such antibodies can serve as therapeutic agents to suppress the inflammatory response by antagonizing the IL-6 pathway, therefore reducing downstream effects like C-reactive protein (CRP) levels, which is a marker of inflammation.\\n\\nConclusively, while the document does not provide direct information on 'Ab_R,' it is likely aligned with therapeutic antibodies targeting cytokine signaling pathways to control inflammation within a modeled biological framework.\"},\n", + " 'background': \"The context provided does not specifically mention the species 'Ab_R' with the ID mw772cbf20_3fc1_4800_ae59_77884f1ae333 located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e. However, the documents discuss the use of antibodies in modulating interleukin pathways, specifically targeting IL-6 and its receptor variants.\\n\\nBased on general knowledge and the context provided, Ab_R might represent an antibody related to the regulation or interaction with the IL-6 pathway or its receptors. \\n\\n1. **Biological Function**: If Ab_R is an antibody, its primary function might be to bind to specific targets, such as antigens or receptors like IL-6, sIL-6Rα, or the IL-6/IL-6R complex, to modulate immune responses or inflammatory pathways.\\n\\n2. **Role in Pathways**: An antibody resembling Ab_R in this context could be involved in reducing inflammation by blocking the interaction between IL-6 and its receptor, preventing downstream signaling and overactivation of the immune response. This could be relevant in the context of diseases with inflammatory components.\\n\\n3. **Interactions with Other Molecules**: Ab_R might interact with proteins like IL-6, its receptors, or complexes such as IL-6/IL-6R, aiming to modulate their activity or presence in the system, leading to changed concentrations of downstream inflammatory markers such as C-reactive protein (CRP).\\n\\n4. **Importance in the Biological System**: In the modeled biological system, such an antibody would be crucial for understanding and predicting therapeutic responses in diseases involving chronic inflammation, autoimmune conditions, or cancer. Its efficacious application could provide insights into novel therapeutic strategies.\\n\\nWhile specific information about 'Ab_R' is not available from the context, the inference aligns it with potentially important roles in immunological regulation through mechanisms of blocking or interacting with cytokine pathways, as seen in therapeutic antibodies targeting the IL-6 signaling axis.\"},\n", " {'id': 'mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf',\n", " 'name': 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)',\n", " 'original_name': 'Ab_sR_IL6',\n", " 'compartment': 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e',\n", - " 'background': \"The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned in the provided context. However, it is possible to infer details about this species based on the context and general knowledge about similar biological components, such as sIL-6R and IL-6.\\n\\n1. **Biological Function**: \\n - Since 'Ab_sR_IL6' likely refers to an antibody (Ab) targeting soluble IL-6 receptor (sIL-6R), its primary function would be to bind soluble IL-6R, potentially inhibiting its interaction with IL-6.\\n\\n2. **Role in Pathways**:\\n - In immune regulation pathways, particularly those involving interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R) can form complexes with IL-6 to mediate signaling even in cells that do not express membrane-bound IL-6R. By targeting sIL-6R, the antibody could disrupt these signaling cascades, serving as a potential therapeutic strategy in diseases characterized by excessive IL-6 signaling, such as rheumatoid arthritis or Crohn’s disease.\\n\\n3. **Interactions with Other Molecules**:\\n - Ab_sR_IL6 would primarily interact with sIL-6R, preventing it from binding to IL-6. This could impede the formation of the IL-6/sIL-6R complex, potentially reducing downstream signaling through the STAT3 pathway and other associated responses, such as C-reactive protein (CRP) production in the liver.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n - In the context of a model focused on immune regulation, particularly in conditions like Crohn’s disease, targeting sIL-6R with an antibody could be critical in modulating the inflammatory response. By acting on the IL-6 signaling pathway, such an approach could help manage systemic inflammation and related symptoms.\\n\\nWhile there is no specific mention of 'Ab_sR_IL6' in the provided documents, understanding its potential role can be inferred based on known dynamics of IL-6, sIL-6R, and their involvement in immune and inflammatory processes.\"},\n", + " 'background': \"The provided context lacks specific information about the species identified as 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, based on general knowledge and the context concerning IL-6 and its soluble receptor sIL-6Rα, we can infer the following:\\n\\n1. **Biological Function**: The molecule 'Ab_sR_IL6' likely functions as an antibody targeting the IL-6/sIL-6R complex. IL-6 is a cytokine involved in inflammatory and immune responses, and sIL-6R is its soluble receptor form. Antibodies targeting these molecules are typically designed to modulate the immune response, particularly in diseases characterized by excessive inflammatory signaling such as Crohn’s Disease.\\n\\n2. **Role in Pathways**: This antibody likely plays a role in blocking or modulating the pathway involving IL-6-mediated signaling. By binding to IL-6 and/or sIL-6R, it prevents their interaction with gp130, a co-receptor necessary for signal transduction, thereby inhibiting downstream signaling effects like the activation of STAT3 and the subsequent transcription of inflammatory genes.\\n\\n3. **Interactions with Other Molecules**: The primary interaction of 'Ab_sR_IL6' would be with IL-6 and sIL-6Rα, limiting their availability to participate in inflammatory signaling. This kind of interaction is often employed to reduce levels of inflammatory mediators like C-reactive protein (CRP) in the circulation.\\n\\n4. **Importance in the Biological System**: In the context of the document, which seems to be related to inflammatory diseases such as Crohn's Disease, the importance of 'Ab_sR_IL6' would be in its potential therapeutic application. By reducing IL-6 signaling, it could help in controlling inflammation and alleviating disease symptoms.\\n\\nIn summary, while specific details about 'Ab_sR_IL6' are not provided, its naming and context imply it is an antibody targeting key components of the IL-6 signaling pathway with potential significance in therapeutic interventions for inflammatory conditions.\"},\n", " {'id': 'mw7becb5fe_8da8_4285_a821_0d77ad811b62',\n", " 'name': 'sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", " 'original_name': 'sR_IL6',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the provided context, there is no specific mention or detailed description of a species or molecule named 'sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, we can infer information about its potential biological role based on general knowledge of similar components in the context of the document, which discusses IL-6 signaling pathways.\\n\\nThe document prominently features IL-6 (Interleukin-6) and its role in the context of immune regulation, particularly in relation to Crohn’s disease. IL-6 is a cytokine involved in inflammation and immune responses. It signals through two main pathways: classical signaling and trans-signaling. In classical signaling, IL-6 binds to its membrane-bound receptor, IL-6R, and subsequently recruits gp130, leading to the activation of downstream pathways such as the JAK/STAT pathway. In trans-signaling, IL-6 can also bind to a soluble form of its receptor, sIL-6R, allowing it to act on cells that do not express membrane-bound IL-6R.\\n\\nGiven the emphasis on IL-6 and sIL-6R in the context, 'sR_IL6' could refer to a soluble receptor or a related soluble component in the IL-6 signaling pathway. This type of molecule typically facilitates trans-signaling interactions. It may interact with IL-6 to form a complex that can then engage with another component, sgp130, to modulate signaling. This complex plays a role in regulating immune responses and could have therapeutic implications, especially in diseases like Crohn’s disease where IL-6 signaling is dysregulated.\\n\\nIn summary, if 'sR_IL6' is indeed related to IL-6 signaling, its biological importance might lie in modulating inflammatory responses through trans-signaling, interacting with IL-6 and possibly other soluble receptors or signaling molecules in this pathway. Its role would be crucial in maintaining homeostasis in immune function and could be a target for therapeutic interventions.\"},\n", + " 'background': \"The species 'sR_IL6' (ID: mw7becb5fe_8da8_4285_a821_0d77ad811b62) located in 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5' likely refers to a soluble receptor component involved in IL-6 signaling pathways. Although the provided context does not give explicit details about 'sR_IL6', we can infer its role based on the mention of 'sIL-6R' and related IL-6 signaling pathways:\\n\\n1. **Biological Function**: 'sR_IL6' is likely a soluble form of the IL-6 receptor, similar to 'sIL-6R'. Soluble receptors often serve to modulate cytokine signaling, either by extending the half-life of the cytokine in circulation, facilitating its transport, or altering its activity. \\n\\n2. **Role in Pathways**: The context suggests that IL-6 signals through both classical and trans-signaling pathways. In the context of immune regulation and Crohn's disease, the IL-6/sIL-6Rα complex is involved in the modulation of inflammatory responses. 'sR_IL6' is expected to participate in these pathways, potentially influencing the interaction with sgp130, a natural inhibitor of the trans-signaling route.\\n\\n3. **Interactions with Other Molecules**: 'sR_IL6' would interact with IL-6, forming complexes that could be sequestered by sgp130, as well as interact with factors involved in immune signaling, such as STAT3, CRP, and possibly others involved in downstream signaling and gene transcription related to immune modulation.\\n\\n4. **Importance in the Biological System**: The role of such soluble receptors is crucial in modulating the availability and activity of cytokines like IL-6. They can influence the strength and duration of signaling in different compartments, vital for maintaining balance in immune responses, particularly in diseases like Crohn's where cytokine signaling can be dysregulated.\\n\\nBased on this inference, 'sR_IL6' appears to be an important modulator within the IL-6 signaling network potentially involved in regulatory mechanisms relevant to inflammation and immune response in the context of Crohn’s disease.\"},\n", " {'id': 'mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca',\n", " 'name': 'gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", " 'original_name': 'gp130',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the provided context, here is the summarized background information about the gp130 species:\\n\\n1. **Biological Function**: gp130 is a protein that plays a critical role in signaling pathways, specifically as part of the interleukin-6 (IL-6) signaling pathway. It acts as a key signal transducer and is involved in the formation of a signaling complex with the IL-6 receptor.\\n\\n2. **Role in Pathways**: gp130 is an integral component of the signaling complex formed between IL-6 and its soluble receptor, sIL-6Rα. The complex formation is crucial for IL-6 trans-signaling, which is implicated in various inflammatory responses.\\n\\n3. **Interactions with Other Molecules**: gp130 interacts with IL-6 and sIL-6Rα to form a hexameric complex that is necessary for initiating the downstream signaling cascade. Soluble gp130 (sgp130) acts as a natural inhibitor by binding to this complex, thereby preventing trans-signaling.\\n\\n4. **Importance in the Biological System**: In the context of the system being modeled, soluble gp130 (sgp130) is considered a potential therapeutic agent, especially in conditions like Crohn's disease, due to its ability to inhibit IL-6 trans-signaling. However, the effectiveness of sgp130 is dependent on achieving high and frequent doses, as small alterations in sgp130 levels have minimal impact due to its high baseline concentration relative to IL-6.\\n\\nOverall, gp130 is pivotal for IL-6-mediated signaling, and modifications in its activity can potentially modulate inflammatory pathways, making it a significant target in certain therapeutic approaches.\"},\n", + " 'background': \"Based on the provided context, the species 'gp130' is involved in the interleukin-6 (IL-6) signaling pathway. Gp130 plays a crucial role as a signal transducer for the IL-6 family of cytokines. It forms a complex with the IL-6/IL-6 receptor (IL-6R) to propagate intracellular signaling leading to various biological responses.\\n\\n1. **Biological Function**: Gp130 is involved in mediating the effects of cytokines, particularly IL-6. It is a part of the receptor complex that includes the IL-6 receptor and gp130. When IL-6 binds to its receptor, gp130 is recruited to form a signaling complex, which then initiates downstream signaling pathways such as JAK/STAT, MAPK, and PI3K/Akt.\\n\\n2. **Role in Pathways**: Gp130 is central to the IL-6 signaling pathway, which is involved in immune responses, inflammation, and cell survival. It is indispensable for the transmission of signals that lead to the activation of transcription factors such as STAT3, which can then affect the expression of various genes involved in inflammatory responses.\\n\\n3. **Interactions with Other Molecules**: Gp130 interacts specifically with the IL-6/IL-6R complex to transmit cytokine-mediated signals. Additionally, soluble forms of gp130 (sgp130) act as natural inhibitors of IL-6 signaling by binding to IL-6/soluble IL-6R complexes, thereby preventing them from interacting with membrane-bound gp130.\\n\\n4. **Importance in the Biological System**: In the context of inflammatory diseases such as Crohn's disease, modulation of gp130 and its associated signaling pathways represents a potential therapeutic strategy. Soluble gp130 (sgp130Fc), a fusion protein combining the extracellular portion of gp130 with an Fc region, has been studied for its ability to inhibit IL-6 trans-signaling, highlighting its therapeutic potential in conditions characterized by excessive or dysregulated IL-6 activity.\\n\\nOverall, gp130 is a critical component of the IL-6 signaling pathway, with its function as both a necessary signal transducer and a target for therapeutic inhibition in inflammatory diseases.\"},\n", " {'id': 'mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9',\n", " 'name': 'R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", " 'original_name': 'R_IL6_gp130',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the context provided, the species named 'R_IL6_gp130' appears to relate to the interleukin-6 (IL-6) signaling pathway, which involves the interaction of IL-6 with its receptor components for signal transduction. Although specific details about this species are not directly provided in the context, we can infer its characteristics and role based on the general knowledge of similar biological components involved in IL-6 signaling:\\n\\n1. **Biological Function**: R_IL6_gp130 likely represents a complex involving IL-6, its specific receptor, and the signal transducer gp130. In the IL-6 signaling pathway, gp130 serves as a critical signal transducer that, upon activation by the IL-6/IL-6 receptor complex, initiates intracellular signaling cascades that influence gene expression.\\n\\n2. **Role in Pathways**: This species is part of the IL-6 signaling pathway, which can activate the JAK/STAT signaling cascade, resulting in the phosphorylation of STAT3 (Signal Transducer and Activator of Transcription 3). This pathway is crucial in mediating inflammatory responses and plays a role in various physiological and pathological processes, including immune regulation, inflammation, and cell growth.\\n\\n3. **Interactions with Other Molecules**: R_IL6_gp130 likely interacts with IL-6 and its soluble receptor (sIL-6R), as well as with gp130. This interaction forms a complex that facilitates signal transduction through the gp130 component, leading to downstream effects such as the activation of STAT3. It can also interact with inhibitors like soluble gp130 (sgp130) or fusion proteins designed to modulate this signaling pathway.\\n\\n4. **Importance in the Biological System**: Within the context described, R_IL6_gp130 is important for understanding the dynamics of IL-6 signaling, especially in inflammatory conditions such as Crohn's disease. The IL-6 pathway is targeted for therapeutic intervention, suggesting its significance in disease pathology and treatment.\\n\\nIn summary, R_IL6_gp130 likely represents a key component of the IL-6 signaling pathway, central to mediating the effects of IL-6 through gp130 in inflammation and immune response, as inferred from the general function of similar complexes.\"},\n", + " 'background': \"Based on the context and information provided, the specifics about the species named 'R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' are not directly detailed. However, by piecing together related information and general knowledge, we can infer some aspects of its characteristics and role in biological systems:\\n\\n1. **Biological Function**: 'R_IL6_gp130' likely represents the interaction or complex involving the interleukin-6 (IL-6) signaling pathway and the gp130 co-receptor. IL-6 is a cytokine involved in immune responses, inflammation, and hematopoiesis. Gp130 is a signal transducer for cytokines in the IL-6 family and plays a crucial role in transmitting signals from cytokine receptors.\\n\\n2. **Role in Pathways**: The IL-6/gp130 complex is essential in the IL-6 signaling pathway, which influences various biological processes including inflammation, immune response, and acute phase reactions. This pathway can operate through classical signaling using membrane-bound receptors or trans-signaling with soluble receptors and receptors like gp130.\\n\\n3. **Interactions with Other Molecules**: The IL-6 signaling pathway involves interactions between IL-6, soluble IL-6 receptor (sIL-6R), and gp130. It is noted that soluble gp130 (sgp130) can inhibit IL-6 trans-signaling, which suggests that 'R_IL6_gp130' might be relevant in modulating or forming complexes crucial for either inhibiting or promoting the IL-6 signal.\\n\\n4. **Importance in Biological System**: In the context of the system being modeled (likely involving conditions like Crohn's disease), targeting the IL-6/gp130 pathway may have therapeutic implications. Efforts such as using sgp130Fc fusion proteins to inhibit IL-6 trans-signaling highlight the importance of understanding and manipulating this complex in disease models for potential treatment strategies.\\n\\nTherefore, 'R_IL6_gp130' in this context probably signifies a key component or step within the IL-6 signaling pathway, with potential roles in modulating inflammatory responses, significant to modeling diseases like Crohn's disease.\"},\n", " {'id': 'mw6cce2109_0e32_4dd9_98ec_41173e8ef07d',\n", " 'name': 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", " 'original_name': 'Ractive',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the provided context, there appears to be no specific information about the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' within the text. However, the context discusses the IL-6 signaling pathway and its components, particularly focusing on the interactions between IL-6, sIL-6Rα, and therapeutic antibodies, such as the humanized anti-interleukin 6 receptor antibody (tocilizumab). This suggests a theme centered around immune response regulation, specifically in diseases like rheumatoid arthritis and possibly Crohn's disease.\\n\\nIn the absence of specific information about 'Ractive', we can infer its potential role based on the discussed biological components. It is likely that 'Ractive' could be involved in the pathways related to cytokine signaling, immune modulation, or therapeutic interactions similar to those of IL-6 or its receptor complex. Its importance in the system may be linked to modulating immune responses or serving as a target or mediator in therapeutic approaches within the context of the mentioned diseases.\\n\\nIn systems biology modeling, species or molecules like 'Ractive' could be critical for either transmitting signals within a pathway, modifying the activity of other molecules, or acting as a checkpoint or target for drugs designed to alter biological responses in conditions like Crohn's disease or rheumatoid arthritis.\"},\n", + " 'background': \"The provided context does not directly reference the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' or its ID: mw6cce2109_0e32_4dd9_98ec_41173e8ef07d. However, we can attempt to infer its possible characteristics and role based on the general information available in the context, which focuses on IL-6-mediated immune regulation in Crohn's Disease, using a multiscale model.\\n\\n1. **Biological Function:**\\n The document is centered around the regulation of IL-6, interleukin-6, which is an important cytokine involved in inflammatory and immune responses. While Ractive itself is not mentioned, it could potentially be related to or a component interacting within the IL-6 signaling pathways.\\n\\n2. **Role in Pathways:**\\n Since the context enlightens the importance of the IL-6/sIL-6Rα complex in IL-6 signaling, Ractive might play a role in a related or auxiliary pathway, possibly as a regulatory or signaling molecule.\\n\\n3. **Interactions with Other Molecules:**\\n The IL-6 signaling pathway involves interactions between IL-6, IL-6 receptors, sIL-6Rα (soluble IL-6 receptor), and antibodies like tocilizumab (anti-IL-6Rα). It's plausible that Ractive could interact with similar molecules or influence the pathway indirectly.\\n\\n4. **Importance in the Biological System:**\\n Given the context's focus on immune regulation and Crohn's Disease, Ractive could be assumed as an important component in the signaling or regulatory mechanisms within this biological model, potentially influencing cytokine behavior, immune response modulation, or drug interactions.\\n\\nIn summary, while there's no specific information on Ractive, its inferred role might be associated with IL-6 signaling, immune pathway interactions, or drug (such as antibody) responses within the described model of immune regulation.\"},\n", " {'id': 'mw2b255f94_8018_4b99_bde8_918eeac45446',\n", " 'name': 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", " 'original_name': 'STAT3',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the provided context, the species 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is likely referring to the well-known protein STAT3, a signal transducer and activator of transcription 3. Here is the relevant background information about STAT3:\\n\\n1. **Biological Function**:\\n - STAT3 is involved in the phosphorylation process as part of cell signaling. Phosphorylated STAT3 (pSTAT3) is indicative of its active state, which can translocate to the nucleus to act as a transcription factor.\\n - It plays a crucial role in relaying signals from cytokine receptors, like the IL-6 receptor complex, to the nucleus, influencing gene expression.\\n\\n2. **Role in Pathways**:\\n - STAT3 is a central component of the JAK-STAT signaling pathway. Once activated, it typically mediates the effects of cytokines, such as IL-6, contributing to various cellular responses, including growth, differentiation, and survival.\\n - The context mentions its involvement in pathways activated by IL-6, a cytokine that triggers immune responses, inflammation, and acute-phase reactions.\\n\\n3. **Interactions with Other Molecules**:\\n - STAT3 gets activated by cytokines binding to their respective receptors, leading to JAK kinases' activation, which subsequently phosphorylates STAT3.\\n - It interacts with components of the IL-6 receptor family, specifically affecting the pathways involving IL-6 trans-signaling.\\n - The context also suggests interactions involving sIL-6R (a soluble IL-6 receptor) and sgp130 (a soluble form of the co-receptor gp130), where pSTAT3 acts in various compartments like the GI tract and liver depending on cytokine signaling.\\n\\n4. **Importance in the Biological System**:\\n - STAT3 is important in modeling biological systems that involve immune responses or inflammation, such as in the context of Crohn's disease, as indicated by increased pSTAT3 levels in serum and tissues affected by the disease.\\n - Its role as a transcription factor makes it key in regulating downstream gene expression that could contribute to disease pathology and the body's response to inflammation.\\n\\nIn summary, although there is no direct mention of a species specifically labeled 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' in the document, the general characteristics and functions of STAT3 can be inferred based on common scientific knowledge and the provided context about IL-6 signaling and related pathways.\"},\n", + " 'background': 'Based on the available context from the provided documents, STAT3 appears to refer to \"signal transducer and activator of transcription 3\". This molecule is a critical component in the JAK/STAT signaling pathway, which is involved in transducing extracellular signals into cellular responses. The context mentions that phosphorylation of STAT3 is important, suggesting that it becomes activated through the addition of a phosphate group. Activated or phosphorylated STAT3 (pSTAT3) can then translocate to the nucleus where it functions as a transcription factor regulating the expression of various genes.\\n\\n**Biological Function:**\\nSTAT3 plays a key role in mediating the effects of various cytokines and growth factors by regulating gene expression. It is involved in controlling multiple cellular processes such as cell growth, apoptosis, and differentiation.\\n\\n**Role in Pathways:**\\nSTAT3 is a central player in the JAK/STAT signaling pathway. It is specifically mentioned in the context of IL-6 signaling, where it is activated downstream of interleukin-6 receptor engagement, which can involve both classical and trans-signaling mechanisms.\\n\\n**Interactions with Other Molecules:**\\nSTAT3 interacts with IL-6 and its receptors (such as sIL-6R and gp130), and phosphorylation of STAT3 can be triggered by cytokines binding to these receptors. The document implies interactions with components like C-reactive protein (CRP) and possibly engagements involving soluble forms of receptors like sgp130, which can modulate signaling.\\n\\n**Importance in the Biological System Being Modeled:**\\nSTAT3\\'s significance in the biological model investigated (likely related to inflammatory diseases like Crohn’s disease) lies in its role in mediating cytokine signaling that could lead to inflammation and other immune responses. The upregulation of phosphorylated STAT3 in specific tissue biopsies, such as those from the colon in Crohn’s disease, suggests its involvement in inflammatory pathogenic mechanisms.\\n\\nOverall, STAT3 is a crucial component in understanding how intracellular pathways translate external signals into gene expression changes that affect biological outcomes and diseases.'},\n", " {'id': 'mw48867e93_f170_44e8_ac7a_185b23e1bf3b',\n", " 'name': 'pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)',\n", " 'original_name': 'pSTAT3',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the context provided, specific information about the biological species 'pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is not explicitly detailed. However, we can infer its role and significance based on the general knowledge about pSTAT3 and its involvement in biological processes.\\n\\n1. **Biological Function:**\\n - pSTAT3, or phosphorylated STAT3, is a form of Signal Transducer and Activator of Transcription 3 (STAT3) that becomes activated through phosphorylation. This activation enables pSTAT3 to translocate to the cell nucleus, where it functions as a transcription factor, promoting the expression of various genes involved in cell growth, survival, and differentiation.\\n\\n2. **Role in Pathways:**\\n - In the context described, pSTAT3 is associated with IL-6 signaling, which involves classical and trans-signaling pathways. IL-6 is a cytokine involved in immune response, and its interaction with receptors such as IL-6R and gp130 leads to the activation of JAK kinases and subsequent phosphorylation of STAT3 (pSTAT3). This signaling cascade is crucial in mediating responses to inflammation and stress.\\n\\n3. **Interactions with Other Molecules:**\\n - pSTAT3 interacts with the IL-6 receptor complex, including sIL-6R (soluble IL-6 receptor) and sgp130 (soluble gp130). The complex formation and subsequent signaling facilitate various downstream effects. pSTAT3 is known to regulate the expression of suppressor of cytokine signaling (SOCS) proteins and other gene products involved in modulating immune responses.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - pSTAT3 plays a critical role in inflammatory responses, as highlighted by its reported increase in serum concentrations in conditions like Crohn’s disease. It is involved in the transcriptional regulation of acute-phase proteins such as C-reactive protein (CRP) and other gene products that are significant in the immune response and inflammation within the gastrointestinal tract and liver.\\n\\nThis inferred information helps underscore the importance of pSTAT3 in immune modulation and its potential implications in inflammatory diseases, even though specific details about its ID-specific characteristics in the context were not provided.\"},\n", + " 'background': \"The provided context does not contain detailed or specific information about the species pSTAT3 identified by the ID mw48867e93_f170_44e8_ac7a_185b23e1bf3b, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. Therefore, I will provide a summary based on general knowledge about pSTAT3 and its role in biological systems.\\n\\n**Background Information on pSTAT3:**\\n\\n- **Biological Function:**\\n pSTAT3 refers to the phosphorylated form of the STAT3 protein, which stands for Signal Transducer and Activator of Transcription 3. STAT3 is a transcription factor that, when phosphorylated, becomes activated and dimerizes. This activated dimer can then translocate to the nucleus to modulate the expression of specific target genes.\\n\\n- **Role in Pathways:**\\n STAT3 is primarily involved in the JAK-STAT signaling pathway. Upon activation, typically through cytokine signaling such as IL-6, STAT3 is phosphorylated by Janus kinases (JAKs). pSTAT3 plays a crucial role in mediating responses to extracellular signaling and is involved in various biological processes such as cell growth, differentiation, and survival.\\n\\n- **Interactions with Other Molecules:**\\n pSTAT3 interacts with JAKs as part of its activation. It is also involved in crosstalk with other signaling molecules and pathways, including IL-6, sIL-6R (soluble IL-6 receptor), and gp130. These interactions facilitate a range of cellular responses, including modulation of immune response, inflammation, and cellular proliferation.\\n\\n- **Importance in the Biological System:**\\n pSTAT3 is an important mediator in immune responses and inflammation. It has been implicated in various diseases, including inflammatory bowel diseases like Crohn's disease, where increased levels of pSTAT3 have been observed in affected tissues. It also plays a role in cancer progression, where aberrant STAT3 activity contributes to tumorigenesis.\\n\\nIn the context of the document, mention of pSTAT3 suggests its potential involvement in IL-6 signaling pathways, possibly related to immune and inflammatory responses as well as transcriptional regulation of genes relevant to the conditions being discussed (e.g., Crohn’s disease or similar inflammatory conditions).\"},\n", " {'id': 'mw0083d743_836f_4238_a17f_4602193d5bc0',\n", " 'name': 'geneProduct',\n", " 'original_name': 'geneProduct',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"The provided context from the document does not include specific details about the biological species or molecule identified as 'geneProduct' with the ID: mw0083d743_836f_4238_a17f_4602193d5bc0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. There is no explicit mention of this molecule's biological function, role in pathways, interactions with other molecules, or its importance in the biological system being modeled.\\n\\nBased on the context, which predominantly discusses interleukin-6 (IL-6) pathways, receptors, and related molecules (e.g., sIL-6R, gp130, and sgp130), we can infer that 'geneProduct' might be related to the IL-6 signaling pathway or another signaling molecule involved in inflammatory or immune responses. In systems biologically concerned with inflammation or cytokine signaling, such gene products might typically be involved in cell signaling cascades, playing roles in activating transcription factors, interacting with receptors or co-receptors, and affecting the expression of downstream genes important for cellular responses.\\n\\nSince specific data is not available, hypothetical pathways could involve roles similar to those of IL-6 or its receptors—modulating inflammatory responses, and participating in acute phase reactions, including CRP production in the liver. Gene products in such pathways often interact with other cytokines, receptors, and intracellular signaling proteins to exert their effects, potentially influencing processes like cell proliferation, differentiation, and survival.\"},\n", + " 'background': \"The provided context does not specifically describe the species named 'geneProduct' with the ID 'mw0083d743_836f_4238_a17f_4602193d5bc0' located in 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5'. However, based on the general context and common knowledge within systems biology, we can infer some plausible information about 'geneProduct' in relation to similar biological components:\\n\\n1. **Biological Function**: Given that 'geneProduct' is mentioned in the context of IL-6 signaling and STAT3 activation, it could be a gene product related to cytokine signaling pathways. Gene products involved in this pathway typically play roles in immune responses, inflammation, cell survival, and proliferation.\\n\\n2. **Role in Pathways**: The context includes references to IL-6, sIL-6R, and associated signaling pathways, such as those involving STAT3 and SOCS. 'geneProduct' may be involved in modulating these pathways, possibly influencing downstream effects such as gene transcription.\\n\\n3. **Interactions with Other Molecules**: 'geneProduct' might interact with key proteins and receptors in the IL-6 signaling pathway, such as IL-6, sIL-6R, gp130, and sgp130. These interactions could be crucial for the regulation and fine-tuning of the signaling pathway.\\n\\n4. **Importance in the Biological System**: If 'geneProduct' participates in IL-6 signaling, it could be important for processes like acute phase responses, immune regulation, and potentially in the context of diseases where IL-6 plays a role, such as autoimmune disorders or chronic inflammatory conditions.\\n\\nWithout specific information, these inferences are speculative but based on common roles and interactions seen within such pathways.\"},\n", " {'id': 'mwd31f52cc_04e7_40e0_885f_c7b2d9e62215',\n", " 'name': 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", " 'original_name': 'sR',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the context provided, there is no explicit mention of the species 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' directly in the excerpts. However, we can infer some related information using general knowledge and by examining the related components and interactions in the context shared.\\n\\nThe context revolves around the interaction and dynamics involving the Interleukin-6 (IL-6) signaling pathway, soluble IL-6 receptor (sIL-6R), and the involvement of other molecules like sgp130. \\n\\n### Inferred Background Information about 'sR':\\n\\n1. **Biological Function:**\\n - In the context of cytokine signaling, receptors like sR are generally involved in recognizing and binding to specific signaling molecules (e.g., cytokines such as IL-6) to facilitate their biological functions. Therefore, 'sR' could act as a receptor or part of a receptor complex in signaling pathways.\\n\\n2. **Role in Pathways:**\\n - Given the presence of IL-6 and its receptor dynamics (e.g., IL-6/sIL-6R complex) in the context, 'sR' might participate in cytokine signaling pathways, potentially serving as a modulator that enhances or inhibits signal transduction depending on its specific interactions with IL-6 or other pathway components like sgp130.\\n\\n3. **Interactions with Other Molecules:**\\n - The sIL-6R forms complexes with IL-6, which then interact with membrane-bound receptors to initiate signaling cascades like the activation of STAT3. 'sR' might potentially interact similarly, indicating a critical role in modifying the intensity or outcome of the signaling process.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - The balance of soluble receptors and cytokines (such as IL-6/sIL-6R) and their interactions with other molecules (e.g., sgp130) are essential for controlling inflammatory responses and other downstream effects (e.g., CRP production in the liver).\\n - Given this, 'sR' could play a pivotal regulatory role, affecting the system's sensitivity to changes in cytokine levels and potentially serving as a target for therapeutic interventions.\\n\\n### Conclusion:\\n\\nWhile the provided document excerpts do not explicitly detail 'sR's identity or function, its inferred associations with key players like IL-6, sIL-6R, and sgp130 suggest a role in cytokine signaling modulation, particularly in pathways relevant to inflammation and immune response. For specific molecular functions and pathway roles, further examination of full-length documents or additional sources would be required.\"},\n", + " 'background': \"Based on the provided context, there is specific mention of an interaction between sR and IL-6. Although the document does not explicitly describe the species labeled as 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)', we can infer its potential role and importance by drawing parallels to similar entities mentioned in the system's model involving IL-6 signaling.\\n\\n### Inferred Information about sR:\\n\\n- **Biological Function**: \\n - The 'sR' is likely a soluble receptor or receptor component involved in the IL-6 signaling pathway, given its contextual relationship with IL-6 and similar naming conventions to 'sIL-6R' and its complex with IL-6 ('IL-6:sR').\\n\\n- **Role in Pathways**:\\n - It seems to participate in modulating IL-6 activity. The mention of 'IL-6:sR' implies that the sR might form complexes with IL-6, influencing the signaling dynamics, possibly acting as a decoy receptor or as a mediator that facilitates or modifies downstream signaling.\\n \\n- **Interactions with Other Molecules**:\\n - The document discusses complexes such as 'IL-6:sR' and 'IL-6:sR:sgp130'. This suggests that sR interacts directly with IL-6 and possibly with other soluble components like sgp130, which is known to modulate IL-6 trans-signaling.\\n\\n- **Importance in the Biological System**:\\n - While sR's specific function was not detailed, its involvement in forming complexes such as 'IL-6:sR' suggests a regulatory role in the IL-6 pathway, which is crucial for inflammatory and immune responses.\\n - The interaction between sR and IL-6 may have implications for therapeutic targets, particularly in conditions where IL-6 signaling is dysregulated.\\n\\nIn summary, 'sR' likely plays a critical part in the IL-6 signaling pathway, influencing the biological effects of IL-6 through complex formation and interaction with other soluble proteins like sgp130. Understanding its role would be important for modeling systemic inflammatory responses and potentially informs therapeutic strategies targeting IL-6 pathways.\"},\n", " {'id': 'mw2c9b0499_3325_4394_8af3_bbf653a944a0',\n", " 'name': 'IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", " 'original_name': 'IL6',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the provided context and general knowledge, the species named 'IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' is likely referring to Interleukin-6 (IL-6), a cytokine involved in various biological functions and pathways. Here is a summary of its roles and significance:\\n\\n1. **Biological Function:**\\n - IL-6 is a multifunctional cytokine that plays a critical role in immune response regulation, inflammation, and hematopoiesis.\\n - It is known to be a mediator of fever and of the acute phase response.\\n\\n2. **Role in Pathways:**\\n - IL-6 signaling occurs via two main pathways: the classical signaling pathway and the trans-signaling pathway.\\n - The classical pathway involves IL-6 binding to a membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of IL-6Rα (sIL-6Rα).\\n - Both pathways converge on a signal transduction cascade that activates Janus kinase (Jak) proteins and leads to the phosphorylation of signal transducer and activator of transcription 3 (STAT3).\\n\\n3. **Interactions with Other Molecules:**\\n - IL-6 interacts with its receptor IL-6Rα (either membrane-bound or soluble) and forms a complex that recruits the gp130 coreceptor.\\n - This interaction is crucial for activating downstream signaling pathways that are involved in immune responses.\\n\\n4. **Importance in the Biological System:**\\n - IL-6 is particularly important in inflammatory diseases such as Crohn's disease, where it contributes to enhanced T-cell survival and resistance to apoptosis in the intestinal mucosa, as well as elevated chemokine secretion.\\n - It plays a significant role in the pathophysiology of autoimmune diseases and chronic inflammatory conditions, making it a target for therapeutic interventions such as with specific antibodies like tocilizumab.\\n\\nIn summary, IL-6 is a central cytokine in immune regulation and inflammatory processes, which makes it a pivotal part of the biological system being modeled, particularly in the context of diseases like Crohn's disease.\"},\n", + " 'background': \"Based on the provided context, IL-6 (likely referring to the cytokine Interleukin-6) is a significant player in the immune regulation associated with Crohn’s disease. Here is a summary of the relevant information extracted about IL-6:\\n\\n1. **Biological Function**: IL-6 is a cytokine that plays a critical role in immune responses. It is involved in the survival of T-cells and contributes to their apoptosis resistance, especially in the lamina propria, a tissue layer in the intestines. This function is particularly relevant in the context of inflammatory diseases such as Crohn's disease.\\n\\n2. **Role in Pathways**: IL-6 signaling can occur through two main pathways:\\n - The **classical pathway**, mediated by a membrane-bound IL-6 receptor (IL-6Rα).\\n - The **trans-signaling pathway**, mediated by a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor to form an active complex that leads to downstream signaling events, including the phosphorylation of Janus kinase (Jak) family proteins and the activation of signal transducer and activator of transcription 3 (STAT3).\\n\\n3. **Interactions with Other Molecules**: IL-6 interacts with its receptor IL-6Rα (both in its membrane-bound and soluble forms) to initiate signaling. In the classical signaling pathway, the IL-6/IL-6Rα complex recruits gp130 to form a functional receptor complex. This interaction initiates a cascade, leading to the activation of downstream signaling molecules, including Jak and STAT3.\\n\\n4. **Importance in the Biological System**: IL-6 is crucial in the modulation of immune responses, which are essential in the context of inflammatory diseases like Crohn’s disease. It enhances the survival of T-cells, contributing to the chronic inflammation characteristic of this condition. The trans-signaling pathway, involving the soluble IL-6Rα, is particularly noted for its importance in disease, highlighting IL-6's role in promoting inflammatory pathways.\\n\\nOverall, IL-6 is depicted as a pivotal cytokine in driving the immune responses that characterize inflammatory diseases, and its pathways and interactions are potential targets for therapeutic intervention.\"},\n", " {'id': 'mwd65b5b39_dc1b_4e77_a999_67277a880e5e',\n", " 'name': 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", " 'original_name': 'sgp130',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the provided context, here is the background information about the species 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)':\\n\\n### Biological Function:\\nsgp130, known here as a species variant, reflects a biological molecule related to the inhibition of IL-6 trans-signaling. It specifically refers to a fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is designed to inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex.\\n\\n### Role in Pathways:\\nsgp130 plays a role in pathways involving the interleukin-6 (IL-6) signaling cascade. It specifically targets the IL-6/sIL-6Rα complex, blocking the trans-signaling pathway that can contribute to inflammatory responses, such as those observed in Crohn’s disease.\\n\\n### Interactions with Other Molecules:\\nsgp130 interacts with the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc binds this complex with the same affinity as natural sgp130, thus inhibiting the signaling pathways mediated by IL-6.\\n\\n### Importance in the Biological System:\\nsgp130 appears to be of limited effect in altering the steady-state values of certain biomarkers unless present in large quantities. It exists in excess compared to free IL-6, leading to minimal effect from small perturbations in its levels. Hence, any significant observable effects require substantial changes in sgp130 concentrations.\\n\\nDespite its biological function, the context suggests that sgp130-based therapeutic strategies may not be as robust as anticipated. The sensitivity analysis indicated that the output biomarkers are less affected by sgp130 levels, making IL-6 and sIL-6Rα more potent targets for intervention in the studied system. This contributes to understanding its therapeutic potential limitations, particularly in addressing diseases like Crohn's where IL-6 signaling is implicated.\"},\n", + " 'background': \"The species or molecule 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' seems to be referring to a soluble form of gp130, which is a component of the IL-6 signaling pathway. Here is a summary of the relevant background information based on the provided excerpts:\\n\\n1. **Biological Function**:\\n - sgp130 functions as an inhibitor of IL-6 trans-signaling, which is a process involving the IL-6 signaling pathway. This occurs when sgp130 binds to the IL-6/sIL-6Rα complex, effectively blocking its ability to signal.\\n\\n2. **Role in Pathways**:\\n - sgp130 is involved in the IL-6 signaling pathway, particularly in the inhibition of IL-6 trans-signaling. This pathway is significant in inflammation and immune response, and it involves interactions with the soluble IL-6 receptor (sIL-6Rα).\\n\\n3. **Interactions with Other Molecules**:\\n - sgp130 interacts with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 prevents IL-6 from engaging with membrane-bound gp130, thus inhibiting downstream signaling events.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n - In the modeling context provided, altering the levels of sgp130 has minimal effect on the system due to its high baseline levels compared to the much lower concentrations of free IL-6. This suggests that while sgp130 is present in excess, significant changes in its levels are required to observe an impact on system outputs.\\n - The effectiveness of sgp130-based therapies appears limited under normal conditions and requires high doses for observable effects, particularly in the suppression of CRP (C-reactive protein) levels and pSTAT3 in the gut.\\n - The sensitivity analysis of the system model indicates that sgp130 is among the least influential parameters for output biomarkers, suggesting that targeting IL-6 and its receptor may be more effective for therapeutic interventions.\\n\\nOverall, sgp130 plays a regulatory role in the IL-6 signaling pathway by acting as a natural inhibitor, but in the context of the model discussed, its predominant presence makes it less impactful for modifying system dynamics without high interventions.\"},\n", " {'id': 'mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3',\n", " 'name': 'sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", " 'original_name': 'sR_IL6_sgp130',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': 'The species sR_IL6_sgp130, identified as mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 within the context provided, appears to involve components related to interleukin-6 (IL-6) signaling pathways. Here is the summary of the background based on the given context and general knowledge:\\n\\n### Biological Function\\n- **Fusion Protein**: The document mentions a fusion protein involving sgp130, which combines the extracellular portion of the gp130 protein with the Fc region of human IgG1. This fusion protein, known as sgp130Fc, is designed to inhibit IL-6 trans-signaling in cells.\\n\\n### Role in Pathways\\n- **IL-6 Trans-Signaling**: The primary role of sgp130Fc is to inhibit IL-6 trans-signaling. In the IL-6 signaling pathway, IL-6 can signal through its receptor complex involving IL-6R and gp130, leading to downstream effects such as the activation of STAT3 transcription factors. The fusion protein acts to prevent this signaling pathway by binding to the IL-6/sIL-6Rα complex.\\n- **Simulations in Crohn’s Disease**: The sgp130Fc protein is being studied for its therapeutic potential in inflammatory conditions like Crohn’s disease, where IL-6 signaling plays a significant role.\\n\\n### Interactions with Other Molecules\\n- **Binding with IL-6/sIL-6Rα Complex**: The sgp130Fc is assumed to bind with the IL-6/sIL-6Rα complex with affinities similar to natural sgp130. The presence of sgp130Fc in large quantities suggests it primarily functions by excess binding to this complex, thereby preventing excessive IL-6 signaling.\\n\\n### Importance in the Biological System\\n- **Therapeutic Potential**: The document outlines the use of sgp130Fc as a potential therapeutic intervention in diseases with aberrant IL-6 signaling, such as Crohn’s disease. It has been shown to only be effective at very high doses due to its interaction landscape.\\n- **Limited Systemic Impact**: Due to high baseline levels of sgp130 compared to IL-6, small changes in sgp130 do not significantly affect the system, implying its role predominantly emerges under conditions requiring high-dose applications or alterations.\\n\\nOverall, while the document primarily discusses the use of a related molecule (sgp130Fc), it emphasizes the relevance of sgp130 interactions within IL-6-related pathways, underscoring its importance in modulating immune and inflammatory responses within certain pathological contexts.'},\n", + " 'background': 'Based on the context provided, there is no specific mention of the species \"sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\" with the ID \"mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3.\" However, we can infer its role and importance based on the information regarding similar biological components described in the context.\\n\\n### Inferred Background Information on sR_IL6_sgp130:\\n\\n1. **Biological Function:**\\n - The molecule seems to relate to the signaling pathway of IL-6 (Interleukin-6), a cytokine important in immune response.\\n - sR_IL6_sgp130 likely involves binding interactions similar to natural sgp130, which acts to inhibit IL-6 signaling by interfering with the IL-6/sIL-6R complex.\\n\\n2. **Role in Pathways:**\\n - It may be involved in pathways such as IL-6 trans-signaling, which is mediated by the soluble IL-6 receptor (sIL-6R) and amplifies responses, particularly in diseases like Crohn\\'s.\\n - It could potentially modulate signaling cascades involving STAT3 (Signal Transducer and Activator of Transcription 3), as IL-6 activates STAT3 through its receptor complexes.\\n\\n3. **Interactions with Other Molecules:**\\n - Likely interacts with components such as IL-6, sIL-6Rα, and sgp130 to modulate signaling.\\n - Its interaction may focus on forming a complex that either facilitates or inhibits further downstream signaling, affecting the activity of proteins like pSTAT3 (phosphorylated STAT3).\\n\\n4. **Importance in the Biological System:**\\n - Given the high baseline level of sgp130 relative to free IL-6, sR_IL6_sgp130 may play a role in maintaining a steady state of signaling through sequestration of signaling complexes.\\n - Its importance could be in contexts requiring modulation of IL-6 activity, either as a natural response or therapeutic intervention, particularly in inflammatory conditions.\\n\\nThis inference is based on the role of similar molecules and the described importance of IL-6 signaling modulation in immunological and inflammatory contexts.'},\n", " {'id': 'mwf7796221_1fea_4274_a93e_c00adbf5778c',\n", " 'name': 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", " 'original_name': 'Ab',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the provided context, there is no specific detailed information available about the species or molecule 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' with the ID mwf7796221_1fea_4274_a93e_c00adbf5778c. However, from the context and general knowledge, we can infer the following:\\n\\n1. **Biological Function**: The document references serum antibody (Ab) concentrations in nmol/l, which suggests that 'Ab' likely stands for an antibody. Antibodies are proteins produced by the immune system to identify and neutralize pathogens such as bacteria and viruses.\\n\\n2. **Role in Pathways**: The context mentions anti-IL-6/sIL-6Rα interactions. Antibodies targeting the interleukin-6 (IL-6) pathway are typically used in treatments to modulate immune responses, particularly in inflammatory conditions. They can bind to IL-6 or its receptor to inhibit the downstream signaling pathway.\\n\\n3. **Interactions with Other Molecules**: The document discusses the anti-IL-6 Ab's effect in relation to IL-6 and sIL-6Rα. This suggests that the antibody in question interacts specifically with these cytokines or cytokine receptors, playing a role in reducing inflammation by interfering with the IL-6 signaling pathway.\\n\\n4. **Importance in the Biological System**: The antibody’s importance seems to be related to its therapeutic role in modulating the immune response, particularly in diseases involving heavy inflammation. This can include conditions like inflammatory bowel diseases or other autoimmune disorders, where targeting IL-6 or its receptor can have significant therapeutic effects.\\n\\nIn summary, based on the context and typical characteristics of antibodies in similar biological systems, 'Ab' is likely an antibody involved in targeting the IL-6 signaling pathway, important for managing inflammatory responses in various conditions.\"},\n", + " 'background': 'Based on the provided context, there is no direct or specific information about the species \\'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)\\'. However, we can infer what this species might be based on general knowledge about similar biological components mentioned in the context.\\n\\nFrom page 5 of the document, we see references to \"anti-IL-6 Ab\" and interactions with \"IL-6Rα/sIL-6Rα\" complexes, which suggest that \\'Ab\\' could potentially be an antibody, possibly involved in targeting IL-6 or its receptor sIL-6Rα in the biological system being studied. \\n\\n**Inferred Biological Function of Ab:**\\n- \\'Ab\\' is likely an antibody that interacts with IL-6 or IL-6Rα. Antibodies are proteins produced by the immune system that can bind to specific antigens, such as proteins on pathogens or other molecules like interleukins.\\n\\n**Role in Pathways:**\\n- The context mentions dose-response changes impacting serum CRP (C-reactive protein), indicating that \\'Ab\\' might play a role in inflammatory pathways, particularly associated with modulating the immune response.\\n\\n**Interactions with Other Molecules:**\\n- If \\'Ab\\' is an anti-IL-6 antibody, its primary interaction would be with interleukin-6 (IL-6) and its receptor complex, IL-6/sIL-6Rα. This interaction can impede the IL-6 signaling pathway, which is involved in inflammation and immune regulation.\\n\\n**Importance in the Biological System:**\\n- The efficacy of \\'Ab\\' in modulating serum CRP levels implies it holds significance in controlling inflammatory responses, potentially offering therapeutic benefits in conditions characterized by excessive inflammation, such as inflammatory bowel diseases or other chronic inflammatory conditions.\\n\\nThis inferred role highlights the importance of \\'Ab\\' in potentially therapeutic contexts where modulation of specific cytokine pathways is desired.'},\n", " {'id': 'mw5d764bb8_5693_4ac8_9557_f65992cc5eb0',\n", " 'name': 'Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", " 'original_name': 'Ab_sR',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"Based on the provided context, there is no specific mention or details about the species named 'Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, I can infer potential roles and functions based on adjacent biological components and typical interactions within such systems, especially considering the discussion around IL-6 pathways and related molecules in the context.\\n\\n1. **Biological Function**: In this particular study context, sIL-6R (soluble Interleukin-6 receptor) and IL-6 (a cytokine involved in inflammation and immune responses) are key components. Ab_sR might refer to an antibody-related soluble receptor component or variant. If related to IL-6/sIL-6R pathways, its function could involve modulation of immune responses or inflammation via binding interactions.\\n\\n2. **Role in Pathways**: The surrounding context heavily discusses the interaction of IL-6 with its receptor and the subsequent signaling pathways, such as the Jak-STAT pathway (notably leading to STAT3 activation), indicating a role in cytokine-receptor interactions. Ab_sR could interact within these pathways, perhaps as an intermediary or a modulator influencing signal transduction.\\n\\n3. **Interactions with Other Molecules**: If analogous to sIL-6R or anti-IL-6 therapeutic antibodies, Ab_sR might interact with IL-6, potentially modulating its effects by altered binding dynamics or competitive inhibition. Such interactions could influence downstream signaling events leading to transcriptional changes (e.g., expression of SOCS or CRP).\\n\\n4. **Importance in Biological System Being Modeled**: In systems modeling inflammatory responses, any component similar to an antibody interacting with cytokines like IL-6 is critical. It could predictively simulate treatment outcomes for inflammatory diseases or evaluate drug efficacy (e.g., CRP suppression in inflammatory cases). Ab_sR may hold similar significance if it's part of experimental or theoretical models assessing cytokine network modulation.\\n\\nWhile these are educated guesses based on typical roles and interactions of analogous proteins within such biological systems, exact functions and roles of Ab_sR would be best determined by specifics from the cited source text.\"},\n", + " 'background': \"The context provided does not include any specific mention of the species named 'Ab_sR' (ID: mw5d764bb8_5693_4ac8_9557_f65992cc5eb0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5). Therefore, I will infer what this species might be based on general knowledge and the context provided.\\n\\nThe context provided mentions interactions around IL-6, sIL-6R (soluble interleukin-6 receptor), and the IL-6/sIL-6R complex, which are significant components in the IL-6 signaling pathway. The mention of molecules such as CRP (C-reactive protein) suggests it is related to inflammatory responses.\\n\\nGiven general biological knowledge, 'Ab_sR' could be hypothesized to represent an antibody or another protein involved in regulating or interacting with soluble receptors like sIL-6R. These soluble receptors often participate in signaling pathways where they modulate the activity of cytokines like IL-6.\\n\\n- **Biological Function**: 'Ab_sR' might function as a regulator in the IL-6 signaling pathway.\\n- **Role in Pathways**: It could play a role in modulating the inflammatory response or could be involved in the same pathway as IL-6/sIL-6R by affecting their interaction or function.\\n- **Interactions with Other Molecules**: It could potentially interact with IL-6, sIL-6R, or related complexes to modulate signaling and downstream effects such as CRP production.\\n- **Importance in the Biological System**: If it is analogous to components like antibodies or receptor regulators, its importance could lie in its potential to modulate immune responses and inflammation.\\n\\nConclusively, without explicit details from the text, we extrapolate that 'Ab_sR' might be involved in related pathways and interactions as a regulatory molecule based on the IL-6/sIL-6R context and general knowledge of similar biological systems.\"},\n", " {'id': 'mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2',\n", " 'name': 'Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)',\n", " 'original_name': 'Ab_sR_IL6',\n", " 'compartment': 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5',\n", - " 'background': \"The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2) does not have specific background information provided explicitly in the context you shared. However, I can infer potential characteristics based on general knowledge about similar components.\\n\\n### Inferred Background Information:\\n\\n1. **Biological Function:**\\n - 'Ab_sR_IL6' likely refers to an antibody ('Ab') targeting the soluble form of the interleukin-6 receptor (sIL-6R). This suggests it is involved in neutralizing or modulating the biological effects of sIL-6R, potentially inhibiting its interaction with interleukin-6 (IL-6).\\n\\n2. **Role in Pathways:**\\n - The context described the targeting of the IL-6/sIL-6R complex as a treatment strategy for conditions involving excessive IL-6 signaling, such as Crohn's disease. 'Ab_sR_IL6' might play a role in suppressing IL-6-mediated pathways, thereby reducing inflammation or immune responses associated with diseases like Crohn's disease or rheumatoid arthritis.\\n\\n3. **Interactions with Other Molecules:**\\n - Interacts with sIL-6R, preventing the formation of the IL-6/sIL-6R complex. This interaction would diminish the activity of the classical and trans-signaling pathways mediated by IL-6, leading to reduced activation of downstream signaling molecules like STAT3 and associated gene transcription.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - Its importance lies in modulating inflammation by impacting IL-6 signaling. As IL-6 is crucial in immune response modulation, controlling its activity can lead to therapeutic benefits in diseases characterized by inflammation and immune dysregulation.\\n\\nBroadly, 'Ab_sR_IL6' serves as a critical component in therapeutic models aiming to attenuate aberrant IL-6 signaling pathways in immune-mediated diseases.\"},\n", + " 'background': \"Based on the provided context, there is no specific mention of the biological species or molecule named 'Ab_sR_IL6' (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3). However, we can infer some relevant details from the general context regarding IL-6 and related pathways.\\n\\n1. **Biological Function**:\\n - IL-6 is a cytokine involved in various immune responses, inflammation, and hematopoiesis. In the provided context, it's part of the signaling pathways that modulate immune responses. \\n\\n2. **Role in Pathways**:\\n - IL-6 interacts with its receptor, IL-6R, and the soluble form sIL-6Rα, to initiate signaling cascades involving pathways such as the JAK/STAT pathway (notably STAT3 phosphorylation). This can lead to the transcription of various genes, impacting inflammation and other immune responses.\\n - The mentioned pathways are part of a model studying IL-6 mediated immune regulation in diseases like Crohn’s disease, emphasizing IL-6's role in immune modulation.\\n\\n3. **Interactions with Other Molecules**:\\n - IL-6 typically binds to its receptor IL-6R or its soluble form sIL-6Rα. This complex can further interact with a signaling receptor gp130 to trigger downstream signaling events.\\n - In therapeutic contexts, antibodies targeting IL-6 or IL-6Rα, such as tocilizumab, interrupt these interactions to modulate immune responses, particularly in inflammatory diseases.\\n\\n4. **Importance in the Biological System Being Modeled**:\\n - The provided context describes a model exploring IL-6/sIL-6Rα interactions, and their targeting implications for modulating immune responses in inflammatory conditions.\\n - The simulations suggest that targeting both IL-6 and the IL-6/sIL-6Rα complex can potentially enhance therapeutic outcomes, highlighting the importance of these interactions in therapeutic strategies.\\n\\nTherefore, if 'Ab_sR_IL6' is related to IL-6/IL-6R interactions, it might be an antibody or related agent involved in modulating these interactions, potentially playing a role in therapeutic interventions for diseases involving IL-6 dysregulation.\"},\n", " {'id': 'mwbc2f5464_81e5_43fd_8b39_f5a2756af72f',\n", " 'name': 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)',\n", " 'original_name': 'Ab',\n", " 'compartment': 'mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87',\n", - " 'background': \"The provided context does not contain direct information specifically about the species 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, from the available information, we can infer some details based on the general context and related biological components mentioned:\\n\\n1. **Biological Function**: The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects like bacteria and viruses. They play a crucial role in targeting specific antigens for the immune response.\\n\\n2. **Role in Pathways**: The context discusses the interaction between anti-IL-6 antibodies and IL-6/sIL-6Rα complex. IL-6 is a cytokine involved in inflammation and infection responses. Hence, antibodies targeting IL-6 pathways are often part of therapeutic interventions for inflammatory diseases.\\n\\n3. **Interactions with Other Molecules**: The document mentions the targeting of IL-6 and IL-6/sIL-6Rα complexes, suggesting that this antibody interacts with these molecules, likely inhibiting their function to reduce inflammation as indicated by the suppression of CRP (C-reactive protein), a marker of inflammation.\\n\\n4. **Importance in the Biological System Being Modeled**: The antibody's role appears to be significant in modulating inflammatory responses by targeting key molecular pathways involving IL-6 and its receptors. This indicates its potential therapeutic value in treating conditions where IL-6 is implicated, such as autoimmune or inflammatory diseases.\\n\\nIn summary, while the antibody 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)' is not directly described in the context, inferred information suggests it likely functions as an IL-6 pathway inhibitor in an inflammatory response model, emphasizing its role in treatment strategies aimed at modulating immune responses.\"}]" + " 'background': \"The provided context does not explicitly mention specific background information or direct details about the species or molecule named 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, based on the surrounding context and general biological knowledge, some inferences can be made:\\n\\n### Inferred Background Information:\\n1. **Biological Function:**\\n - The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins that play crucial roles in the immune system by identifying and neutralizing foreign objects such as bacteria and viruses.\\n\\n2. **Role in Pathways:**\\n - Given the context mentioning IL-6 and IL-6Rα, it is likely that this antibody might be involved in the immune response pathway, possibly targeting components like interleukin-6 (IL-6) or its receptor. This suggests its participation in pathways that modulate inflammation or immune signaling.\\n\\n3. **Interactions with Other Molecules:**\\n - The context suggests interaction or targeting of the IL-6 or IL-6 receptor (IL-6Rα), indicating that this antibody might bind to these molecules, influencing inflammatory processes or immune responses.\\n\\n4. **Importance in the Biological System Being Modeled:**\\n - The system described seems to focus on understanding therapeutic strategies and modeling responses, possibly related to inflammatory diseases like inflammatory bowel diseases (IBDs) or conditions involving cytokines like IL-6. The antibody may be important for modulating these responses as part of a treatment strategy or for experimental observation.\\n\\n### General Inference:\\n- In systems biology, antibodies such as the one referred to, are often used experimentally or therapeutically to modulate biological pathways for research or treatment, particularly in immune response pathways dealing with cytokines. The context of IL-6 pathway targeting implies its significance in diseases managed by controlling inflammation, such as autoimmune or chronic inflammatory diseases. \\n\\nThis inferred summary is based on typical roles and interactions of antibodies in biological research and therapeutic contexts, especially within the immune signaling pathways referenced in the context.\"}]" ] }, "execution_count": 9, @@ -1949,24 +1954,24 @@ "text/plain": [ "['Crohns disease',\n", " 'IL-6',\n", - " 'IL-6R',\n", - " 'sIL-6R',\n", - " 'CRP',\n", + " 'IL-6Rα',\n", + " 'sIL-6Rα',\n", " 'gp130',\n", - " 'Jak',\n", " 'STAT3',\n", + " 'pSTAT3',\n", + " 'Jak',\n", + " 'CRP',\n", + " 'tocilizumab',\n", " 'T-cells',\n", " 'hepatocytes',\n", + " 'lymphocytes',\n", " 'apoptosis',\n", " 'inflammation',\n", - " 'GI tract',\n", + " 'chemokine',\n", + " 'acute-phase proteins',\n", + " 'monoclonal antibodies',\n", " 'sgp130',\n", - " 'tocilizumab',\n", - " 'cytokines',\n", - " 'Janus kinase',\n", - " 'lamina propria',\n", - " 'leukocytes',\n", - " 'chemokine']" + " 'Jak-STAT']" ] }, "execution_count": 10, diff --git a/notebook/species_backgrounds.csv b/notebook/species_backgrounds.csv index 4ae8e0fb..39c3cd8c 100644 --- a/notebook/species_backgrounds.csv +++ b/notebook/species_backgrounds.csv @@ -1,648 +1,653 @@ id,name,original_name,compartment,background -mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The provided context outlines the biological function and role of IL-6, a cytokine important in the immune system. Based on the information: +mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context, IL6 (Interleukin 6) is a cytokine that plays a crucial role in immune regulation, particularly in the context of inflammatory conditions such as Crohn's disease and rheumatoid arthritis. -1. **Biological Function**: - IL-6 is a cytokine involved in immune regulation. It plays a crucial role in enhancing T-cell survival and resistance to apoptosis, particularly in the context of Crohn’s Disease, as well as in promoting chemokine secretion. +### Biological Function: +IL6 is involved in immune responses and inflammation. It contributes significantly to the survival of T-cells and confers resistance to apoptosis in the lamina propria, a layer of the intestinal mucosa, thereby playing an important role in the pathology of inflammatory bowel diseases like Crohn's disease. It is also associated with elevated chemokine secretion. -2. **Role in Pathways**: - IL-6 signaling can proceed via two distinct pathways: - - The classical pathway, which involves the membrane-bound IL-6 receptor (IL-6Rα). - - The trans-signaling pathway, which involves a soluble IL-6 receptor (sIL-6Rα). In both pathways, IL-6 forms a complex with its respective receptor, which then recruits the gp130 coreceptor, leading to the formation of a hexameric receptor complex. This complex initiates phosphorylation of gp130-bound Janus kinase (Jak) proteins and subsequent activation of STAT3 (Signal Transducer and Activator of Transcription 3). +### Role in Pathways: +IL6 signaling can occur through two main pathways: +1. **Classical Pathway**: This involves the membrane-bound IL-6 receptor (IL-6Rα). In this process, IL6 binds to IL-6Rα on the cell membrane, forming a complex that recruits the membrane-bound coreceptor gp130, which forms a heterotrimeric complex. This complex dimerizes into a hexameric receptor complex, activating downstream signaling cascades. +2. **Trans-signaling Pathway**: Here, IL6 binds to a soluble form of IL-6Rα (sIL-6Rα), and this complex also recruits gp130, following a similar mechanism to form an active signaling complex. Trans-signaling is particularly important in pathological conditions where traditional signaling pathways are altered or less efficient. -3. **Interactions with Other Molecules**: - IL-6 interacts with its membrane-bound and soluble receptors to initiate signaling. The interaction sequence involves IL-6 binding to IL-6Rα, recruiting gp130, and activating downstream signaling molecules like Jak family proteins and STAT3. +### Interactions with Other Molecules: +IL6 interacts with both membrane-bound and soluble forms of its receptor IL-6Rα to initiate signaling cascades. The activated receptor complex initiates phosphorylation of Janus kinase (Jak) family proteins, which subsequently phosphorylate signal transducer and activator of transcription 3 (STAT3). This signaling cascade is pivotal in mediating the biological effects of IL6 in inflammatory and immune responses. Additionally, the model demonstrates interactions between IL6, its receptors, and therapeutic antibodies like tocilizumab, which are designed to suppress IL6 signaling. -4. **Importance in the Biological System Being Modeled**: - IL-6 is highlighted as a significant contributor in the pathophysiology of Crohn’s Disease due to its roles in promoting immune cell activities that lead to inflammation. The ability of IL-6 to engage in both classical and trans-signaling pathways suggests it is a versatile mediator in inflammatory processes, making it a critical target for therapeutic interventions. +### Importance in the Biological System Being Modeled: +In the context of Crohn's disease, IL6 is highlighted as a significant mediator of immune regulation, particularly due to its role in enhancing T-cell survival and modulating chemokine secretion, which are key components of the disease's pathology. Targeting IL6 signaling pathways, whether through classical or trans-signaling, could be a therapeutic strategy for managing inflammatory responses associated with Crohn’s disease and similar conditions. -5. **General Knowledge and Inference**: - Beyond the context, IL-6 is generally known to be involved in inflammation and is a key player in various inflammatory diseases. It is a target for drugs like tocilizumab, which inhibit IL-6 signaling by preventing the interaction of IL-6 with its receptor, thus being an important therapeutic strategy in diseases such as rheumatoid arthritis. +In summary, IL6 is a critical cytokine involved in immune regulation and inflammatory signaling, serving as both a potential target for therapeutic intervention and a key player in the pathogenesis of diseases such as Crohn's disease and rheumatoid arthritis." +mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130,sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species 'sgp130' appears to be related to a modified version of the gp130 protein, specifically referred to as sgp130Fc. Here is a summary based on the provided context: -In summary, IL-6 is a multifunctional cytokine central to immune regulation and inflammation, making it a crucial element in disease models, particularly those addressing inflammatory conditions like Crohn's Disease." -mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130,sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the context provided, sgp130 is a biological molecule that plays a role in inhibiting IL-6 trans-signaling. Here is a summary of its background information: +1. **Biological Function**: sgp130 is primarily involved in inhibiting IL-6 trans-signaling. This is achieved by its ability to bind to the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1, has been shown to inhibit this pathway in cultured cells. -1. **Biological Function**: sgp130 is derived from the extracellular portion of the gp130 protein. It serves to inhibit the signaling pathway of interleukin-6 (IL-6) by binding to the IL-6/sIL-6Rα complex, thereby preventing it from activating downstream signaling pathways. This inhibition is achieved by a fusion protein called sgp130Fc, which combines sgp130 with the Fc region of human IgG1. +2. **Role in Pathways**: The primary pathway of interest involving sgp130 is the IL-6 signaling pathway. IL-6 is a cytokine implicated in various inflammatory processes, and its trans-signaling via the soluble IL-6 receptor (sIL-6Rα) is distinct from classical signaling. The role of sgp130 is to regulate this trans-signaling pathway by competing with cell surface gp130 receptors, thereby reducing the pro-inflammatory effects mediated by IL-6/sIL-6Rα. -2. **Role in Pathways**: sgp130 influences the IL-6 signaling pathway, specifically targeting the trans-signaling aspect. IL-6 is a pro-inflammatory cytokine that can signal through a complex with soluble IL-6 receptor (sIL-6Rα) and gp130. By interfering with this pathway, sgp130 can modulate inflammatory responses. +3. **Interactions with Other Molecules**: sgp130 interacts with the IL-6/sIL-6Rα complex. In the presence of high amounts of sgp130, most of the IL-6 is bound, thus preventing it from mediating its effects via the trans-signaling pathway. -3. **Interactions with Other Molecules**: The primary interaction of sgp130 is with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 inhibits its ability to signal through the cell surface-bound gp130, thus blocking IL-6 mediated effects. The interaction between sgp130 and the IL-6/sIL-6Rα complex is central to its function. +4. **Importance in the Biological System**: Despite its potential therapeutic role, the sensitivity analysis from the provided context suggests that sgp130 has a relatively low impact on the steady-state dynamics of the system being modeled. This is attributed to its high baseline concentration compared to IL-6, implying that large changes in sgp130 levels are needed to achieve significant biological effects. Therefore, the efficacy of sgp130-based therapies, like sgp130Fc, may be limited and require high doses to be effective. -4. **Importance in the Biological System Being Modeled**: While sgp130 can effectively inhibit IL-6 trans-signaling, the context indicates that its role in the system being modeled is limited. The sensitivity analysis within the model shows that alterations in sgp130 levels have minimal effects on the steady-state values of output parameters due to the high baseline level of sgp130 compared to the relatively low concentration of free IL-6. This suggests that sgp130-based therapies may not be as impactful unless used at high and frequent doses. The model under discussion aimed at simulating its potential therapeutic use in conditions like Crohn’s disease. +Overall, sgp130 serves as a regulatory molecule within the IL-6 signaling pathway, specifically targeting and mitigating the effects of IL-6 trans-signaling, though its standalone therapeutic potential may be limited due to high baseline levels and lower impact on system sensitivity." +mw810ff751_fa4e_4143_bd50_169b3e325e1e,sR_IL6_sgp130,sR_IL6_sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species 'sR_IL6_sgp130' appears to be involved in the system of IL-6 signaling, which plays a critical role in inflammatory responses such as those found in diseases like Crohn's disease. Based on the provided context, here's a summary of its background information: -Overall, sgp130 is important for modulating IL-6 trans-signaling, but in the specific system modeled, its impact is limited under normal conditions due to its already high concentration compared to IL-6." -mw810ff751_fa4e_4143_bd50_169b3e325e1e,sR_IL6_sgp130,sR_IL6_sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context from the document, 'sR_IL6_sgp130' seems to be a part of the IL-6 signaling pathway and is likely a reference to a complex involving soluble IL-6 receptor components. Here's a summary based on the information provided and general knowledge: +1. **Biological Function**: sR_IL6_sgp130 is likely related to the IL-6 signaling pathway. It is suggested to be a complex involving soluble IL-6 receptor (sIL-6R) and sgp130, which is a fusion protein comprised of the extracellular portion of the gp130 receptor and the Fc region of human IgG1. The gp130 receptor is part of the signaling pathway for IL-6, a cytokine involved in immune responses. -- **Biological Function:** The complex is involved in modulating IL-6 signaling, particularly influencing the trans-signaling mechanism. Soluble gp130 (sgp130) acts as a natural inhibitor of IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing it from associating with membrane-bound gp130, which is necessary for signal transduction. +2. **Role in Pathways**: sR_IL6_sgp130 is involved in the inhibition of IL-6 trans-signaling. This pathway is crucial for mediating pro-inflammatory responses. The context suggests that sgp130 can bind to the IL-6/sIL-6Rα complex, potentially blocking further signaling within this pathway. -- **Role in Pathways:** It is a critical modulator in the IL-6 signaling pathway. Normally, IL-6 binds to the soluble IL-6 receptor (sIL-6R), and this complex can further engage with gp130 on cell surfaces to propagate downstream signaling events. The sgp130 serves as a sink for these IL-6/sIL-6R complexes, limiting their ability to bind to cellular gp130 and hence reducing downstream signaling such as STAT3 activation. +3. **Interactions with Other Molecules**: The species interacts with IL-6 and sIL-6Rα. The fusion protein sgp130Fc has been shown to bind to the IL-6/sIL-6Rα complex, suggesting that sR_IL6_sgp130 may act to sequester this complex and prevent it from engaging with cell surface receptors, thereby inhibiting downstream signaling, including pSTAT3 activation. -- **Interactions with Other Molecules:** The complex interacts primarily with IL-6 and its soluble receptor (sIL-6R). It prevents these molecules from engaging with cell-surface gp130, thus acting as a competitive inhibitor in the pathway. +4. **Importance in the Biological System Being Modeled**: Despite its role in inhibiting IL-6 signaling, sensitivity analyses indicate that altering sgp130 levels has a minimal effect on the steady-state dynamics of the system due to its high baseline concentration. This suggests that while sR_IL6_sgp130 has the potential to influence inflammation pathways, its impact may be limited under normal conditions and would require significant changes to yield observable effects. -- **Importance in the Biological System:** In the context of the system being modeled, sgp130 is crucial as it regulates the balance of IL-6 signaling. Its high baseline concentration relative to IL-6 suggests it plays a stabilization role in keeping the system responsive only to significant changes in IL-6 levels. However, its effectiveness as a therapeutic agent, such as in Crohn’s disease, may require high and frequent dosing due to its large baseline presence and minimal effect on system dynamics under normal conditions. +Overall, sR_IL6_sgp130 represents an important therapeutic target or molecule within the context of IL-6 mediated diseases, but its natural abundance and resultant low system sensitivity under basal conditions make it a challenging target for effective therapeutic intervention without substantial dosage alterations." +mw114aa90f_5f5b_4fe8_9406_361c8489b6a1,CRP,CRP,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"C-reactive protein (CRP) is a crucial protein in the context of inflammation and immune response regulation. Based on the provided context and general knowledge about CRP, the following summarizes its biological role and significance: -No direct information about 'sR_IL6_sgp130' as a separate distinct entity is found in the context, suggesting it might be inferred from understanding sgp130's complex with IL-6 and sIL-6R within the described signaling and therapeutic contexts." -mw114aa90f_5f5b_4fe8_9406_361c8489b6a1,CRP,CRP,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The term 'CRP' within the context provided refers to C-reactive protein, rather than a distinct biological species. C-reactive protein is a well-known biomarker present in the bloodstream, often used to assess inflammation within the body. Here's a summary of relevant background information about CRP based on the context and general biological understanding: +1. **Biological Function**: + - CRP is an acute-phase protein, primarily produced in the liver in response to inflammation. It is commonly used as a marker to assess inflammatory states in various conditions. The production is typically induced by cytokines such as interleukin-6 (IL-6). -- **Biological Function**: C-reactive protein is an acute-phase protein produced by the liver in response to inflammation. Its primary role is to bind to the surface of dead or dying cells (and some types of bacteria) to activate the complement system, thereby promoting phagocytosis by macrophages. This function is part of the body's innate immune response, aiding in clearing pathogens and dead cells from the bloodstream. +2. **Role in Pathways**: + - CRP plays a part in the systemic response to inflammation, often used clinically as an indicator for inflammatory conditions such as infections and autoimmune diseases. In the context described, CRP levels are used to monitor and model the effect of treatments targeting components of the IL-6 signaling pathway, especially in diseases like Crohn's disease. -- **Role in Pathways**: CRP is part of the body's acute-phase response to inflammation. Its levels in the blood increase rapidly in response to inflammatory cytokines, such as interleukin-6 (IL-6). This makes CRP an integral component in pathways related to the immune system's response to infection, injury, or chronic inflammatory diseases. +3. **Interactions with Other Molecules**: + - CRP interacts with various components of the immune system. It can bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system, promoting phagocytosis by macrophages, which is a crucial aspect of its role in inflammation. + - In the context of the presented data, CRP levels are modulated through pathways involving IL-6 and its receptor (IL-6Rα), showcasing its interconnected role in immune signaling pathways. -- **Interactions with Other Molecules**: CRP interacts with the complement system components, particularly C1q, to initiate the complement cascade, a series of reactions that help eliminate pathogens. It also interacts with receptors on the surfaces of immune cells, such as Fcγ receptors, facilitating opsonization and phagocytosis. The document mentions interactions with IL-6 and its receptor IL-6Rα, as CRP production is highly influenced by IL-6 signaling. +4. **Importance in the Biological System Being Modeled**: + - Within the model described, CRP serves as a key biomarker for the effectiveness of treatment strategies targeting IL-6 signaling. The modulation of CRP levels indicates the level of inflammation and the success of therapeutic interventions aimed at reducing inflammation by inhibiting IL-6 activity. + - The document suggests the use of CRP levels to validate and predict the outcomes of therapeutic interventions, underlining its importance as a measurable outcome in clinical and modeling studies. -- **Importance in Biological Systems**: In the context of the model described, CRP is used as a biomarker to assess inflammation levels in patients, particularly those with conditions such as Crohn's disease. The model measures CRP levels to validate its predictions regarding drug effects on inflammatory pathways, highlighting its utility in monitoring disease activity and treatment efficacy. +Overall, CRP acts as an essential biomarker and participant in inflammatory pathways, and its levels are indicative of the inflammatory state and the impact of medical treatments in the studied model." +mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc,sR,sR,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context, there is limited direct information regarding the species 'sR' with ID mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc. However, we can infer some details based on the context of similar biological components mentioned. -Overall, CRP is a crucial component in biological models focused on inflammatory diseases due to its rapid and measurable response to changes in underlying inflammation." -mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc,sR,sR,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context, the species named 'sR' (ID: mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc) is likely related to the IL-6 signaling pathway. However, specific details about 'sR' are not provided directly in the context. Given that 'sR' is mentioned alongside IL-6, sIL-6R, and sgp130, it could be inferred that 'sR' is a component or modifier in the interleukin-6 (IL-6) signaling pathway. +1. **Biological Function**: The context does not specify a unique biological function for 'sR'. However, it mentions interactions involving IL-6 and sIL-6R, suggesting that 'sR' might be associated with receptor or signaling functions in the IL-6 pathway. sIL-6R usually stands for soluble IL-6 receptor, which is involved in extending the effects of the IL-6 cytokine beyond cells that have membrane-bound receptors. -### Inferred Background Information +2. **Role in Pathways**: Similar to sIL-6R and other molecules like sgp130, 'sR' might play a role in the modulation of signaling pathways. IL-6 signaling pathways involve activation and modulation through receptors, influencing gene transcription and protein production. It's plausible that 'sR' participates in similar pathways, potentially affecting signal transduction and biological responses. -**Biological Function**: -- It is probable that 'sR' is related to IL-6 signaling, potentially as a soluble receptor or co-receptor. Soluble receptors often exist as naturally occurring antagonists or helpers of cytokine signaling, modulating the pathway's activity. +3. **Interactions with Other Molecules**: Although not directly mentioned, 'sR' perhaps interacts with other components in the IL-6 signaling cascade such as IL-6, its receptors (like IL-6R), and possibly soluble receptors like sgp130. Intermediates such as Jak and STAT3 are common in such pathways, and 'sR' might influence or be influenced by these interactions. -**Role in Pathways**: -- 'sR' might be involved in modulating the availability or activity of IL-6, similar to how sgp130 and sIL-6R work. sIL-6R is known to allow cells that do not possess membrane-bound IL-6R to respond to IL-6 through a process known as trans-signaling. +4. **Importance in the Biological System**: The significance of 'sR' is not explicitly described, but it could be an important regulator within the system. Given the extensive discussion on IL-6 and its modulation by soluble receptors and sgp130, 'sR' might contribute to these dynamics, affecting cellular responses to IL-6 signaling and influencing conditions like inflammatory responses or chronic disease states. -**Interactions with Other Molecules**: -- It may interact with IL-6 or IL-6 receptor complexes. This interaction is crucial in the modulation of the pathway, likely affecting the downstream signaling events such as the activation of STAT3 (Signal Transducer and Activator of Transcription 3). +In summary, while not directly detailed, 'sR' may operate similarly to other receptors or molecules in the IL-6 signaling context, playing a part in modulation, interaction, and systemic effects within biological pathways." +mw03db56ac_8dc6_4931_ae82_fef706d2ee3d,sR_IL6,sR_IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species ""sR_IL6,"" identified by the ID mw03db56ac_8dc6_4931_ae82_fef706d2ee3d, is likely related to the soluble interleukin-6 receptor (sIL-6R) based on the context provided. Here is an interpretation and breakdown of its role and function: -**Importance in the Biological System**: -- Given its potential role in cytokine signaling, 'sR' would be important in regulating inflammatory responses, immune system signaling, and possibly in the pathophysiology of diseases where IL-6 is a key player, such as autoimmune diseases. +1. **Biological Function**: + - sR_IL6 is likely analogous to sIL-6R, which functions as a part of the IL-6 signaling pathway. The soluble receptor binds to interleukin-6 (IL-6), facilitating its interaction with gp130, an essential component for signal transduction. -### Contextual Consideration -- The provided context includes a discussion on sensitivity analysis and the role of sgp130 with IL-6, which highlights the intricate balance within the cytokine signaling pathways. Though 'sR' is not explicitly expanded upon, understanding the dynamics of similar molecules like sIL-6R and sgp130 offers insights into its potential biological significance. - -This inferred information aligns with typical roles of soluble cytokine receptors in biological systems. However, the exact nature and function of 'sR' would require further specific details or experimental data." -mw03db56ac_8dc6_4931_ae82_fef706d2ee3d,sR_IL6,sR_IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species labeled 'sR_IL6' in the context provided appears to refer to a soluble receptor for interleukin-6 (IL-6), often denoted as sIL-6R. Soluble IL-6 receptors play a crucial role in IL-6 trans-signaling pathways, which differ from classical signaling by involving the soluble receptor form (sIL-6R) rather than the membrane-bound IL-6 receptor (IL-6R). +2. **Role in Pathways**: + - IL-6 can signal through classical and trans-signaling pathways. In the classical pathway, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), while in the trans-signaling pathway, the soluble receptor (sIL-6R) binds IL-6, allowing the complex to interact with gp130 on cells that do not express IL-6R. This interaction is crucial for activating downstream signaling pathways, such as the JAK/STAT pathway, specifically promoting STAT3 phosphorylation (pSTAT3), which can lead to gene transcription including the acute phase protein C-reactive protein (CRP). -### Biological Function: -- **Soluble IL-6 Receptor (sIL-6R):** Its primary function is to bind to the cytokine IL-6, forming a complex that can activate cells that do not have membrane-bound IL-6 receptors. This process is known as ""trans-signaling"" and allows for a wider range of cells to respond to IL-6, expanding its biological effects. +3. **Interactions with Other Molecules**: + - sR_IL6 (sIL-6R) interacts directly with IL-6 to form the IL-6/sIL-6R complex. This complex can be sequestered by the soluble gp130 (sgp130), inhibiting the signaling and potentially modulating the intensity or range of the IL-6 mediated response. -### Role in Pathways: -- **Trans-signaling Pathway:** In trans-signaling, the IL-6/sIL-6R complex associates with the membrane protein gp130, facilitating intracellular signaling cascades such as the JAK/STAT pathway. This activation leads to gene transcription and biological responses in target cells. -- **Classical Signaling Pathway:** sIL-6R is involved in sequestering IL-6 in the presence of the regulatory protein sgp130, modulating the signaling capacity by preventing excessive inflammatory signaling. +4. **Importance in the Biological System**: + - The IL-6/sIL-6R complex plays a role in immune regulation, as indicated by its involvement in models studying conditions like Crohn’s disease. It has significance in how inflammation is managed within the body, especially in the context of inflammatory diseases. + - The model indicates the regulation of sR_IL6 levels may impact therapeutic strategies, with alterations in dosages of anti-IL-6 antibodies showing variable efficacy. -### Interactions with Other Molecules: -- **IL-6:** The soluble receptor interacts with IL-6 to initiate trans-signaling. -- **gp130:** Binds the IL-6/sIL-6R complex, essential for downstream signal transduction. -- **sgp130:** Acts as a natural inhibitor by sequestering IL-6/sIL-6R complexes, dampening potential overactivation of IL-6 signaling. +Overall, the sR_IL6 is a critical component in mediating IL-6 trans-signaling, thus having a significant impact on immune regulation and potential therapeutic strategies for inflammatory diseases." +mwf345ed7a_0622_403c_b816_c8749a2c9ded,Ab,Ab,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context from the documents, the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded, located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e) is likely referring to an antibody, given the context in which it's mentioned, particularly in relation to drug doses and targeting of specific molecular complexes. -### Importance in the Biological System: -In the context of Crohn's disease and immune regulation, the IL-6/sIL-6R complex plays a critical role. Modulating this pathway can influence disease progression and therapeutic outcomes. Targeting the IL-6/sIL-6R complex could offer promising treatments by adjusting the immune response and inflammation characteristic of the condition. +Here are the inferred details about 'Ab' based on the context: -The context suggests that sIL-6R could be involved in a model for chronic inflammatory conditions, highlighting its significance in promoting or inhibiting inflammation through different signaling pathways. By understanding its interactions and functions, potential strategies can be developed for therapeutic interventions, such as using antibodies to modify its activity." -mwf345ed7a_0622_403c_b816_c8749a2c9ded,Ab,Ab,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided documents, there isn't direct and specific information regarding the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded) in the given context. However, based on general knowledge and context clues, 'Ab' likely refers to an antibody, given the reference to serum Ab concentrations and interaction with IL-6 and sIL-6Rα complexes. +- **Biological Function**: The antibody ('Ab') likely functions in binding to specific target molecules, probably related to the immune system or inflammation pathways, as inferred from the association with IL-6/sIL-6Rα complexes—the interleukin-6 receptor alpha complex. -1. **Biological Function**: Antibodies (Ab) are proteins produced by the immune system that recognize and bind to specific antigens, such as pathogens (viruses, bacteria) or other target molecules. Their primary function is to neutralize these antigens and facilitate their destruction by other immune cells. +- **Role in Pathways**: 'Ab' seems to play a role in modulating pathways related to inflammatory responses, especially through interactions with the IL-6 signaling pathway. It appears to be part of a therapeutic strategy, potentially targeting cytokines such as IL-6 and its soluble receptor complex to regulate inflammation, as noted by the mention of CRP suppression (C-reactive protein—a marker for inflammation). -2. **Role in Pathways**: In the context provided, 'Ab' is involved in targeting the IL-6 and IL-6Rα pathways. This is indicative of its role in modulating inflammatory responses, likely through the inhibition of the IL-6 signaling pathway. +- **Interactions with Other Molecules**: The context suggests a role in interacting with IL-6 and sIL-6Rα complexes. The antibody serves as a limiting factor in neutralizing or modulating these complexes within the biological system, influencing serum biomarker levels like CRP. -3. **Interactions with Other Molecules**: The document mentions the anti-IL-6 Ab dose response and its effects on serum CRP suppression. The interaction specifically involves the binding of the antibody to IL-6 and the IL-6/sIL-6Rα complex, which suggests its use in blocking or reducing the inflammatory signaling mediated by these molecules. +- **Importance in the Biological System Being Modeled**: 'Ab' is significant in the modeled system as a therapeutic agent, potentially used in treating inflammatory conditions by targeting cytokine pathways. By affecting IL-6-related pathways, it appears to reduce inflammatory responses, as evidenced by experiments and modeling of serum CRP suppression following treatments. -4. **Importance in the Biological System**: The blocking or modulation of IL-6 signaling by antibodies plays a significant role in managing inflammatory diseases. The context implies that targeting IL-6 and its receptor complexes can be part of a therapeutic strategy for conditions characterized by excessive inflammation, such as inflammatory bowel diseases. +Though specific details about 'Ab' are not explicitly provided in the excerpts, it can be inferred that 'Ab' is a therapeutic antibody with a function in targeting pro-inflammatory cytokine pathways within the given biological context, aiming to control or reduce inflammatory processes." +mw1da111f2_a036_4392_8512_015005bdcbb7,Ab_sR,Ab_sR,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context, specific information about the species ""Ab_sR"" (ID: mw1da111f2_a036_4392_8512_015005bdcbb7, located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e) is not directly mentioned. However, we can infer its potential role and importance in the biological system being modeled by examining the surrounding biological components and pathways mentioned in the context. -Given these points, 'Ab' in this context seems to be associated with therapeutic antibodies used to manage inflammation by interfering with specific cytokine pathways, particularly involving IL-6. This type of intervention is crucial in diseases where cytokine signaling contributes to the pathology." -mw1da111f2_a036_4392_8512_015005bdcbb7,Ab_sR,Ab_sR,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The specific species 'Ab_sR' (ID: mw1da111f2_a036_4392_8512_015005bdcbb7) located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e does not seem to be explicitly mentioned in the provided context. However, based on the context and general knowledge, we can infer some relevant background information about similar biological components that usually appear in such contexts. +### Inferred Background Information about Ab_sR -The context mentions components such as sIL-6R, IL-6, and their interactions, which are indicative of a role in inflammatory response pathways. sIL-6R is a soluble form of the IL-6 receptor, and it typically participates in what's known as IL-6 trans-signaling. In this process, instead of the membrane-bound receptor, IL-6 binds to sIL-6R to form a complex that can interact with the gp130 protein, initiating signaling cascades even in cells that do not express the full receptor. This mechanism is important in regulating immune responses, inflammation, and possibly chronic inflammatory diseases by influencing the production of acute-phase proteins like C-reactive protein (CRP). +1. **Biological Function:** + - The context suggests a focus on interleukin-6 (IL-6) and its receptor interactions, particularly involving the soluble IL-6 receptor (sIL-6R) and its complexes. Given the naming convention ""Ab_sR,"" it is reasonable to infer that Ab_sR could represent an antibody (Ab) specific to a soluble receptor (sR), likely related to the IL-6 signaling pathway. -Given this understanding, 'Ab_sR' could potentially refer to an antibody or an interaction factor related to the soluble receptor pathways, possibly playing a regulatory or inhibitory role in these pathways through binding interactions. Its importance might then be deduced from its capability to modulate these signaling pathways, with potential therapeutic implications for diseases driven by excessive IL-6 signaling. +2. **Role in Pathways:** + - The IL-6 signaling pathway involves several key interactions, including the formation of complexes with sIL-6R, which are critical for signal transduction. Ab_sR might participate in modulating or inhibiting this pathway, possibly by binding to the sIL-6R or other pathway components, potentially altering the pathway's output like the downstream effects on C-reactive protein (CRP) production. -If Ab_sR is an antibody, it could play a role similar to antibodies against IL-6 or IL-6Rα, aiming to disrupt or modify these signaling pathways, potentially reducing inflammatory responses as a therapeutic strategy. Such antibodies are being explored in contexts of autoimmune diseases, cancers, and inflammatory disorders. +3. **Interactions with Other Molecules:** + - Within the pathway context, Ab_sR may interact with IL-6, sIL-6R, and possibly other related components like the glycoprotein (gp130), which are crucial for IL-6 signal transduction. Its role might be to bind these molecules to modulate their activity or bioavailability in the system, akin to the action of therapeutic antibodies that target cytokine receptors. -Note: This inference is made based on the context provided and common biological functions of related components. Further specific information would be required for more accurate detailing of Ab_sR's role." -mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac,Ab_sR_IL6,Ab_sR_IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The context provided does not directly specify information about a species named 'Ab_sR_IL6'. However, based on general knowledge and the context given, we can make some inferences and provide related information: +4. **Importance in the Biological System:** + - Ab_sR could be significant for fine-tuning the inflammatory response mediated by IL-6 signaling. By regulating or inhibiting the function of the IL-6/sIL-6R pathway, Ab_sR might contribute to controlling inflammation and related processes in tissues such as the liver and gastrointestinal tract. This modulation could be especially important in conditions where IL-6 plays a pivotal role, such as in autoimmune diseases or chronic inflammatory states. -1. **Biological Function**: Given the naming convention used ('Ab_sR_IL6'), it is likely that this refers to an antibody (Ab) targeting a soluble receptor (sR) for interleukin-6 (IL-6), possibly inhibiting its action. IL-6 is a cytokine involved in inflammatory and immune responses. +Overall, while direct information on Ab_sR is not available, the context allows us to hypothesize its role as a regulatory or inhibitory agent within the IL-6 signaling pathway, potentially serving as a therapeutic molecule targeting inflammation-related pathways." +mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac,Ab_sR_IL6,Ab_sR_IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the context provided, there is no specific mention of the species 'Ab_sR_IL6' by name. However, the context revolves around interactions involving IL-6, its receptor sIL-6Rα, and antibodies targeting these molecules. We can infer certain characteristics and roles this species might fulfill based on the general knowledge of similar biological components and the information presented: -2. **Role in Pathways**: IL-6 typically signals through its receptor complex, including IL-6R and gp130, to activate downstream signaling pathways like JAK/STAT, leading to the activation of transcription factors such as STAT3. This cascade leads to the expression of various genes involved in inflammation and immune regulation. +1. **Biological Function**: Proteins associated with the suffix 'Ab' usually refer to antibodies. Given the context, 'Ab_sR_IL6' likely functions as an antibody targeting the IL-6 receptor, specifically the soluble form sIL-6Rα. Antibodies like these are typically designed to bind to their target receptor, potentially blocking its interaction with its ligand (IL-6) or other molecules, resulting in modulation of a biological pathway. -3. **Interactions with Other Molecules**: Based on the context, the antibody could be interacting with the IL-6/sIL-6R complex to modulate its effects. The text describes interactions involving sIL-6R and IL-6, potentially including competition or inhibition by antibodies that alter the signaling outcomes and inflammatory responses. +2. **Role in Pathways**: In the immune regulation context, this antibody likely plays a role in modulating IL-6-mediated signaling pathways. The data discusses targeting the IL-6/sIL-6Rα complex to modulate responses in the immune system, particularly in inflammatory conditions like Crohn’s Disease and rheumatoid arthritis. By interfering with this pathway, the antibody likely serves to suppress the pro-inflammatory effects mediated by IL-6. -4. **Importance in the Biological System Being Modeled**: In the context of the model described, inhibiting the IL-6/sIL-6R interaction is a focus, likely due to its role in conditions like Crohn's Disease or rheumatoid arthritis. Modifying this pathway's activity through an antibody such as 'Ab_sR_IL6' might be of therapeutic significance, potentially helping to suppress excessive inflammatory responses, as suggested by the interest in CRP (C-reactive protein) suppression and dose-response relationships. +3. **Interactions with Other Molecules**: The document specifically talks about the interaction of antibodies with sIL-6Rα and IL-6, suggesting that 'Ab_sR_IL6' could interact with these components. The interaction with sIL-6Rα likely prevents the receptor from associating with IL-6 or gp130 (another crucial signaling component). This interference can result in reduced signaling through the JAK-STAT pathway, which is implicated in inflammation and autoimmune disease processes. -In summary, 'Ab_sR_IL6' is likely conceptualized as an antibody targeting the soluble IL-6 receptor to interfere with IL-6 mediated signaling pathways, which are pivotal in certain inflammatory diseases. While specific details are not provided in the context, this inference aligns with common therapeutic strategies involving cytokine signaling modulation." -CRP_Suppression___,CRP Suppression (%),CRP Suppression (%),mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the context provided, ""CRP Suppression (%)"" refers to the measurement of the reduction in serum C-reactive protein (CRP) levels. CRP is a biological marker of inflammation, and its levels can be indicative of inflammatory responses in the body. Understanding the suppression of CRP levels has the following implications: +4. **Importance in the Biological System**: The importance of such an antibody in the model is likely related to its ability to control inflammatory processes. By targeting sIL-6Rα, it could help reduce the production of inflammatory mediators like C-reactive protein (CRP) and other gene products important in the inflammatory response. In the context of diseases like Crohn’s Disease, the use of such an antibody could be significant for reducing symptoms and controlling disease progression. -1. **Biological Function**: CRP is an acute phase protein, produced by the liver in response to inflammation. It plays a role in the body's immune response, indicating tissue damage or inflammation. +Given these points, 'Ab_sR_IL6' likely represents a therapeutic antibody targeted towards IL-6 signaling components, playing a crucial role in modulating immune responses in inflammatory diseases." +CRP_Suppression___,CRP Suppression (%),CRP Suppression (%),mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"CRP Suppression (%) refers to the extent to which the levels of C-reactive protein (CRP) in the serum are reduced from baseline levels. CRP is a biomarker typically used to assess inflammation and is often elevated in response to inflammatory conditions such as infections, chronic diseases, or autoimmune disorders. -2. **Role in Pathways**: CRP is involved in the inflammatory pathway. Suppressing CRP levels typically suggests an underlying modulation of the inflammatory response, often facilitated through interventions like antibodies targeting specific inflammatory cytokines or receptors, such as IL-6 or IL-6Rα in this context. +### Biological Function: +- **C-reactive protein (CRP):** CRP is a protein produced by the liver in response to inflammation. It is part of the body's immune response and acts as an opsonin, marking pathogens for destruction by immune cells. -3. **Interactions with Other Molecules**: The context implies interactions with Interleukin-6 (IL-6) and its receptor (IL-6Rα). Treatments with anti–IL-6 or anti–IL-6Rα antibodies reduce CRP levels, thereby modulating inflammation, as indicated by the provided data on drug dose and CRP suppression. +### Role in Pathways: +- **Inflammatory Pathways:** The suppression of CRP levels is a marker of reduced inflammation. In the context of treatments targeting cytokines like interleukin-6 (IL-6), the decrease in CRP is an indicator of the efficacy of such anti-inflammatory treatments. -4. **Importance in the Biological System**: Suppression of serum CRP is an important indicator of the efficacy of drugs, like anti-IL-6 or anti-IL-6Rα antibodies, in reducing inflammatory responses. This makes CRP suppression a critical measure for evaluating the outcome of therapeutic interventions aimed at inflammatory diseases. +### Molecular Interactions: +- **Interaction with Interleukin-6 (IL-6):** IL-6 is a cytokine that stimulates CRP production. Anti-IL-6 or anti-IL-6 receptor therapies aim to reduce CRP levels by blocking the action of IL-6, thereby diminishing its signal for CRP synthesis. -While the context does not directly describe CRP Suppression (%) as a biological species, it is a measure of the effectiveness of treatments targeting inflammatory pathways. Interactions that lead to its suppression are essential for understanding therapeutic impacts on inflammation-related conditions." -CRP____of_baseline,CRP (% of baseline),CRP (% of baseline),mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The term ""CRP (% of baseline)"" is referring to C-reactive protein (CRP) levels measured as a percentage of a baseline value. In the context provided, it appears to be a metric used in the modeling and analysis of clinical trial data related to anti–IL-6Rα antibody treatments, specifically tocilizumab, which is an anti-inflammatory medication. Here's a summary based on the context and general knowledge about CRP: +### Importance in the Biological System Being Modeled: +- **Treatment Efficacy Marker:** CRP Suppression (%) is used as a biomarker to evaluate the effectiveness of treatments, such as anti-IL-6 antibodies or anti-IL-6R antibodies, in reducing inflammation. The suppression percentage directly correlates with the reduction in inflammatory activity within the body. +- **Dose-response Analysis:** The relationship between drug dosage and CRP Suppression (%) is crucial for determining optimal dosing regimens. Increased CRP suppression with higher doses of anti-inflammatory drugs typically indicates greater efficacy, though it may plateau or saturate at certain dose levels. -1. **Biological Function:** - - CRP is a protein produced by the liver in response to inflammation. It is part of the acute phase response to inflammation and is a biomarker commonly used to assess inflammation and tissue injury. +In summary, CRP Suppression (%) serves as a critical indicator for assessing the impact of therapeutic strategies aimed at managing inflammatory responses by targeting specific immune signaling pathways in the body." +CRP____of_baseline,CRP (% of baseline),CRP (% of baseline),mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the context provided and general knowledge about C-reactive protein (CRP), I can summarize the following background information: -2. **Role in Pathways:** - - CRP is a key player in the acute inflammatory response and is involved in pathways that react to injury, infection, and inflammation. It interacts with the immune system to facilitate the clearance of necrotic and apoptotic cells and bacteria. +1. **Biological Function**: + - CRP, or C-reactive protein, is a substance produced by the liver in response to inflammation. It is a member of the class of acute-phase proteins, which increase in concentration in response to inflammation. CRP is commonly measured in clinical settings as a marker of inflammation. -3. **Interactions with Other Molecules:** - - CRP levels are influenced by the presence of pro-inflammatory cytokines, particularly interleukin-6 (IL-6). This context highlights the interaction between CRP levels and anti–IL-6Rα antibodies, which inhibit IL-6 signaling and therefore can suppress CRP production as part of their therapeutic action. +2. **Role in Pathways**: + - CRP is part of the body's immune response and plays a role in recognizing pathogens and damaged cells, thereby promoting their clearance through interaction with the complement system and other immune pathways. The context involving IL-6 and anti–IL-6Rα antibody treatment suggests an interest in inflammatory pathways where CRP is a downstream marker of cytokine (like IL-6) activity. -4. **Importance in the Biological System Being Modeled:** - - In the given context, CRP (% of baseline) serves as an important biomarker for evaluating the efficacy of tocilizumab treatment in suppressing inflammation. The model uses CRP levels to compare and validate simulation results against clinical trial data, indicating its critical role in assessing treatment impacts. +3. **Interactions with Other Molecules**: + - CRP interacts with phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) to activate the complement system. It is known that CRP levels are regulated by cytokines, particularly interleukin-6 (IL-6), which is relevant in the context of anti-IL-6 therapy described in the document. + +4. **Importance in the Biological System Being Modeled**: + - The suppression and modulation of serum CRP levels are used as a measure to validate models simulating the effects of anti-IL-6Rα antibody therapy (such as with tocilizumab) in clinical settings. In this context, CRP (% of baseline) acts as a biomarker to assess the efficacy of treatment options targeting inflammatory pathways and the IL-6 signaling axis. It indicates the level of inflammation within patients undergoing such treatments. -No specific unique details beyond this general framework are detailed in the context, but from a systems biology perspective, CRP measurement is significant for understanding inflammatory processes and the body's response to therapeutic interventions." -mw80848184_e2dd_47ce_86d7_7a21479342bd,gp130,gp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species named 'gp130' refers to a protein that plays a significant role in the signaling pathway involving interleukin-6 (IL-6) and its receptor. +The reference to CRP (% of baseline) reflects normalized data used to compare changes in serum CRP levels over time, particularly in response to medical interventions, such as administration of anti-inflammatory drugs. This emphasizes its utility as a reliable marker for evaluating treatment responses in clinical trials and models related to inflammatory diseases." +mw80848184_e2dd_47ce_86d7_7a21479342bd,gp130,gp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, the biological species named 'gp130' appears to be a critical component in the interleukin-6 (IL-6) signaling pathway. Here's a summary of its role and importance: ### Biological Function: -- **gp130 is a Signal Transducer**: It is primarily a signal-transducing component of the IL-6 receptor complex. It does not bind IL-6 by itself but acts as a signal transducer when associated with IL-6 and IL-6 receptor (IL-6R). +- **Gp130** serves as a signal-transducing coreceptor in the IL-6 signaling pathway. +- It acts as part of a complex with the IL-6 receptor (IL-6R) and is involved in mediating the downstream effects of IL-6. ### Role in Pathways: -- **Interaction with IL-6/IL-6R**: gp130 is crucial in the formation of the signaling complex with IL-6 and its soluble receptor sIL-6R. This complex is central to IL-6 signaling pathways. -- **Inhibition of IL-6 Trans-Signaling**: A fusion protein known as sgp130Fc, which combines the extracellular portion of gp130 with an Fc region, has been shown to inhibit IL-6 trans-signaling, demonstrating gp130’s role in regulatory mechanisms. +- **IL-6 Signaling**: Gp130 is a key component in the assembly of the IL-6/IL-6R/gp130 complex. This is crucial for the signaling cascade that drives various inflammatory and immune responses. +- **Inhibition of IL-6 Trans-Signaling**: The soluble form of gp130 (sgp130) can inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing its interaction with membrane-bound gp130 and subsequent signaling. ### Interactions with Other Molecules: -- **Complex Formation**: It forms a complex with IL-6 and IL-6R, contributing to signal transduction. -- **Natural Inhibitor**: Soluble gp130 (sgp130) serves as a natural inhibitor of the IL-6/sIL-6R signaling pathway, preventing excessive signal transduction. +- **IL-6 and IL-6R**: Gp130 interacts with IL-6 bound to its receptor IL-6R, forming a complex necessary for initiating signal transduction. +- **Soluble IL-6 Receptor (sIL-6R)**: It is noted that sgp130 is a natural inhibitor of the soluble IL-6 receptor, indicating a regulatory role in modulating the availability and activity of IL-6. ### Importance in the Biological System: -- **Regulatory Role**: The high baseline level of soluble gp130 (sgp130) in the system acts as a buffering agent against changes in the levels of IL-6/sIL-6R complex, highlighting its regulatory importance. -- **Therapeutic Potential**: Therapeutic approaches using sgp130 to target IL-6 signaling pathways, such as in the treatment of Crohn’s disease, underscore its clinical significance. - -Given these roles, gp130 is a critical component in the IL-6 signaling pathway and has potential therapeutic implications due to its regulatory capacities in controlling inflammatory responses." -mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a,R_IL6_gp130,R_IL6_gp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species named 'R_IL6_gp130', based on its naming and the context provided, likely refers to a complex or interaction involving the cytokine interleukin-6 (IL-6) and the signal transducer glycoprotein 130 (gp130). While the specific document does not provide detailed information about R_IL6_gp130, general knowledge about the IL-6/gp130 interaction helps us understand its potential biological significance. +- Gp130 is vital for the modulation of immune responses and inflammation through its role in IL-6 signaling. +- **Therapeutic Potential**: Its soluble form, sgp130, has been studied for therapeutic applications, including its potential use in diseases characterized by excessive IL-6 signaling, such as Crohn's disease. The context mentions simulations of sgp130Fc (a fusion protein of sgp130 with the Fc region of an antibody) for therapeutic dosing. +- **Baseline Levels**: The high baseline levels of sgp130 compared to IL-6 indicate its prominent regulatory role in the signaling environment. -### Biological Function: -- **IL-6:** It is a cytokine involved in the regulation of immune responses, inflammation, and hematopoiesis. It plays a crucial role in acute phase responses and is produced at sites of inflammation. -- **gp130:** It serves as a signal transducer in the cytokine receptor complex, particularly for the IL-6 family of cytokines. It is involved in several cellular processes, including cell growth and differentiation. +In summary, gp130 is a crucial component of the IL-6 signaling pathway with significant implications in inflammation and immune modulation. Its interactions and regulatory capabilities make it a target for therapeutic intervention, especially in inflammatory diseases." +mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a,R_IL6_gp130,R_IL6_gp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context and general knowledge about similar biological components, the species 'R_IL6_gp130' likely refers to a complex involving interleukin-6 (IL-6), its receptor (IL-6R), and the signaling component gp130. Here's a summary of what is generally known about the components involved: -### Role in Pathways: -- The IL-6/gp130 interaction is central to both classical and trans-signaling pathways. In classical signaling, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), which then associates with gp130 to initiate downstream signaling. -- In trans-signaling, IL-6 binds to a soluble form of the IL-6 receptor (sIL-6R), and this complex can then associate with gp130 on the target cell surface, allowing cells that do not express membrane-bound IL-6R to respond to IL-6. +1. **Biological Function:** + - Interleukin-6 (IL-6) is a cytokine involved in immune responses, inflammation, and hematopoiesis. It mediates its effects through the IL-6 receptor (IL-6R) and the signal transducer gp130. + - gp130 is a transmembrane protein that, upon IL-6 binding to IL-6R, forms a complex through which signal transduction occurs, initiating intracellular signaling cascades primarily involving the JAK-STAT pathway. -### Interactions with Other Molecules: -- gp130 is a common subunit shared by several cytokine receptors in the IL-6 family, meaning it participates in a variety of signaling complexes. -- The soluble form of gp130 (sgp130) can act as a natural inhibitor by binding to IL-6/sIL-6R complexes and preventing them from interacting with membrane-bound gp130. +2. **Role in Pathways:** + - The IL-6/IL-6R/gp130 signaling complex plays a crucial role in the JAK-STAT signaling pathway. This pathway is pivotal in promoting gene expression associated with inflammatory responses. + - The pathway can occur through classical signaling, where IL-6 binds to its membrane-bound receptor IL-6R, or through trans-signaling, where IL-6 binds to a soluble form of IL-6R (sIL-6R), interacting with membrane-bound gp130 in cells that do not express IL-6R. -### Importance in the Biological System Being Modeled: -- Given the context of inflammatory diseases such as Crohn’s disease, the IL-6/gp130 axis is likely a critical component in the inflammatory response modulation. -- The application of sgp130, or its fusion forms like sgp130Fc, demonstrates the pathway's therapeutic significance as a target for damping excessive IL-6-mediated signaling in inflammatory diseases. +3. **Interactions with Other Molecules:** + - IL-6 binding to IL-6R and subsequent interaction with gp130 triggers gp130 dimerization and activation of associated JAK kinases, leading to phosphorylation and activation of STAT3, a transcription factor. + - Soluble gp130 (sgp130) can inhibit IL-6-mediated trans-signaling by binding to the IL-6/sIL-6R complex, preventing it from interacting with membrane-bound gp130. This natural inhibitor is significant as it selectively inhibits the trans-signaling pathway. -In summary, R_IL6_gp130 refers to a key interaction in the IL-6 signaling pathway, emphasizing its role in inflammatory responses and its potential as a therapeutic target in autoimmune diseases like Crohn's." -mw4638f126_8cb8_4021_ab41_6ae195743ba0,"sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context and general knowledge, here is the background information on the species 'sR_IL6' with the identifier 'mw4638f126_8cb8_4021_ab41_6ae195743ba0', situated within 'mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e': +4. **Importance in the Biological System Being Modeled:** + - The IL-6/gp130 signaling axis is critical in inflammatory diseases, including Crohn's disease and other autoimmune conditions. The document highlights the therapeutic potential of modulating this pathway, particularly using sgp130Fc (a fusion protein analog of gp130) to inhibit IL-6 trans-signaling. + - Pharmacokinetic (PK) studies and simulations of sgp130Fc are mentioned, indicating its evaluation as a therapeutic intervention targeting this pathway, aiming to reduce inflammation markers like CRP (C-reactive protein) and pSTAT3 in the gut. -1. **Biological Function**: 'sR_IL6' likely refers to the soluble receptor for Interleukin-6 (sIL-6R). Soluble receptors such as sIL-6R can bind to the cytokine IL-6, acting as a co-receptor that allows IL-6 to engage in signaling pathways even in cells that do not express the membrane-bound IL-6 receptor. +In summary, 'R_IL6_gp130' likely represents a signaling complex crucial for mediating inflammatory responses in various biological settings, making it a significant therapeutic target, especially in inflammatory and autoimmune diseases." +mw4638f126_8cb8_4021_ab41_6ae195743ba0,"sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The molecule in question, sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2), can be inferred to relate closely to soluble IL-6 receptor components based on its name and ID positioning within a model of IL-6 signaling. Although there is no explicit information about this exact species in the provided context, some relevant points about similar molecules can be derived. -2. **Role in Pathways**: In the immune system, IL-6 can signal through two main pathways: - - **Classical signaling**: IL-6 binds to membrane-bound IL-6R and recruits the gp130 protein to initiate downstream signaling. - - **Trans-signaling**: sIL-6R, in complex with IL-6, engages gp130 on cells that do not have the IL-6 receptor, thus expanding the range of cells that can respond to IL-6. This is particularly relevant in inflammatory responses and is studied in contexts such as Crohn's disease. +### **Biological Function:** +- **sIL-6R (soluble IL-6 receptor)**: Typically, sIL-6R refers to a soluble form of the IL-6 receptor, which allows IL-6 to transduce signals through cells that do not express the membrane-bound IL-6 receptor. This process is part of what is known as IL-6 trans-signaling. In the context of the model being described, sR_IL6 may play a similar role. -3. **Interactions with Other Molecules**: - - sIL-6R forms a complex with IL-6 which can then bind to gp130, leading to activation of downstream signaling pathways such as the JAK/STAT pathway. - - sIL-6R can be sequestered by sgp130, a soluble form of gp130, which can regulate the availability of the IL-6/sIL-6R complex for signaling. - - C-reactive protein (CRP) is involved in the production of sIL-6R through a process known as CRP-mediated shedding. +### **Role in Pathways:** +- **IL-6 Signaling**: It functions within the IL-6 signaling pathway, which can occur via classical signaling or trans-signaling. Classical signaling involves membrane-bound IL-6R and gp130, while trans-signaling involves sIL-6R. +- **Interaction with sgp130**: The sIL-6R/IL-6 complex can be sequestered by another molecule, sgp130, preventing further signaling. -4. **Importance in the Biological System**: - - sIL-6R plays a crucial role in mediating IL-6 trans-signaling, particularly in contexts like chronic inflammation and autoimmune diseases such as Crohn's disease. - - The presence of sIL-6R enables IL-6 to exert its effects even in cells lacking direct IL-6 receptors, thereby widening its scope of action within the immune regulatory processes. - - Understanding the dynamics of sIL-6R in combination with IL-6 is important for therapeutic considerations, as targeting these complexes can influence pharmacological outcomes in disease states. +### **Interactions with Other Molecules:** +- **IL-6/sIL-6R Complex**: It forms a complex with IL-6, which can engage with gp130 on cell membranes, activating downstream signaling cascades. +- **CRP Influence**: The production of sIL-6R is influenced by CRP (C-reactive protein), which mediates its shedding. -Thus, sR_IL6 (inferred as sIL-6R) is integral to the IL-6 signaling pathways, facilitating broad immunological responses through its role in trans-signaling and interaction with IL-6 and other molecular regulators like sgp130." -mw10315fa3_6f13_4618_bda8_a8694bd3c374,R,R,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Given the context provided, the information about the species named 'R' (ID: mw10315fa3_6f13_4618_bda8_a8694bd3c374) is not directly mentioned in the documents. However, we can make inferences based on the information about related molecules and pathways described in the context, particularly those involving IL-6 (interleukin-6) and its receptor. +### **Importance in the Biological System Being Modeled:** +- **Crohn’s Disease**: The IL-6/sIL-6Rα complex plays a significant role in the context of Crohn’s disease, a chronic inflammatory condition. Therapeutic strategies targeting this complex have been simulated to evaluate their effects on disease dynamics. +- **Pharmacological Efficacy**: In therapeutic models, blocking the IL-6/sIL-6Rα complex alongside free IL-6 has been shown to improve pharmacological efficacy, implying its critical role in modulating immune responses. -### Inferred Background Information about 'R': +In summary, sR_IL6 is likely involved in facilitating trans-signaling in IL-6 pathways, interacting with other components like IL-6, gp130, and CRP, with implications for inflammatory diseases such as Crohn’s disease. These inferred roles suggest its significance in the physiological and pathological contexts of IL-6 mediated immune regulation." +mw10315fa3_6f13_4618_bda8_a8694bd3c374,R,R,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The provided context refers to interactions and functions related to the interleukin-6 receptor (IL-6R), yet there is no explicit mention of a species or molecule specifically called 'R'. However, we can infer that 'R' might refer to the interleukin-6 receptor (IL-6R) or components associated with it based on the context of the documents provided. Here's a summary of relevant information that could be applicable to 'R', especially if it is related to IL-6R: 1. **Biological Function**: - - Since the context discusses IL-6 and its receptors (sIL-6R and IL-6Rα), 'R' could potentially be related to components in the IL-6 signaling pathway. IL-6 is a cytokine involved in inflammation and immune response regulation. + - The IL-6 receptor (IL-6R) plays a critical role in the immune response. It is involved in the signaling pathway for interleukin-6 (IL-6), a cytokine that influences immune regulation, inflammation, and hematopoiesis. 2. **Role in Pathways**: - - IL-6 interacts with both membrane-bound and soluble forms of its receptor (IL-6R) to initiate downstream signaling cascades, such as the JAK/STAT pathway, which leads to the activation of transcription factors like STAT3 (signal transducer and activator of transcription 3). - - The pathway is involved in the transcription of various genes, including those coding for acute-phase proteins like CRP (C-reactive protein), indicating a role in inflammatory processes and liver function. - + - IL-6R is a part of the Classical and Trans signaling pathways. In the Classical pathway, it binds IL-6, leading to dimerization with gp130 and activation of the JAK/STAT signaling cascade, particularly resulting in the phosphorylation and activation of STAT3. This pathway has significant implications for transcriptional regulation of various genes. + - The IL-6 trans-signaling involves soluble IL-6R (sIL-6R) and affects cells that do not naturally express IL-6R on their surface, further enabling broader physiological effects. + 3. **Interactions with Other Molecules**: - - IL-6, in combination with its receptor, can activate a signaling complex that involves the JAK proteins and STAT3, influencing gene expression. Soluble forms of the receptor, such as sIL-6R, play a role in trans-signaling, which can modulate responses in cells that do not express the membrane-bound receptor. + - IL-6R interacts with IL-6 and gp130 in both the Classical and Trans signaling pathways. + - Antibodies targeting IL-6R, such as those mentioned in the context (e.g., anti–IL-6Rα antibodies), are used to modulate its function, particularly as therapeutic interventions to reduce inflammation or lower C-reactive protein (CRP) levels. 4. **Importance in the Biological System**: - - Given that IL-6 signaling impacts acute-phase response and immune regulation, molecules within this pathway, including 'R' if it is part of this system, are crucial for modulating inflammatory responses. They may be targeted in therapeutic contexts, such as with anti–IL-6 or anti–IL-6Rα therapies, which are indicated in the documents as treatments influencing biomarkers like CRP. + - In the context of disease and therapy, IL-6R is a target for modulating inflammatory responses, as its activation leads to increased levels of acute-phase proteins such as CRP, which are markers for inflammation. + - The modulation of IL-6R, such as through the use of antibodies, is significant in clinical settings for managing conditions characterized by excessive inflammation or immune activation. -In conclusion, without specific data directly linked to 'R', it can be inferred that 'R' is potentially part of the IL-6 pathway components, involved in immune and inflammatory responses, and plays a significant role in cellular signaling and communication within this biological system." -mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1,"IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, the species referred to as 'IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is likely Interleukin-6 (IL-6), a cytokine involved in various biological processes. Here is a summary of relevant background information about IL-6: +Based on the described interactions and importance, if 'R' refers to the IL-6 receptor or a similar component, it acts as a central mediator in inflammatory pathways and is a critical target for therapeutic interventions." +mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1,"IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided and general knowledge about IL-6, here is a summary of the information regarding IL-6, particularly in the context of immune regulation and diseases like Crohn's disease: -1. **Biological Function:** - - IL-6 is a cytokine that plays a crucial role in immune regulation. It is involved in the inflammatory response and is essential for the body's defense against infections and injuries. +1. **Biological Function**: IL-6 is a cytokine that plays a critical role in the immune system. It is involved in the regulation of immune responses, inflammation, and hematopoiesis. IL-6 is an important mediator in the body's response to infections and tissue injuries, helping to stimulate immune response. -2. **Role in Pathways:** - - IL-6 signaling can occur through two main pathways: - - **Classical Pathway:** This involves the membrane-bound IL-6 receptor (IL-6Rα) where IL-6 binds to IL-6Rα, forming a complex that recruits a membrane-bound gp130 coreceptor, triggering downstream signaling cascades. - - **Trans-signaling Pathway:** This involves the soluble IL-6 receptor (sIL-6Rα). The IL-6/sIL-6Rα complex can associate with gp130 to initiate signaling in cells that do not express the membrane-bound IL-6Rα. This pathway is particularly important in inflammatory diseases. +2. **Role in Pathways**: IL-6 signaling occurs via two main pathways: + - The classical pathway, mediated by the membrane-bound IL-6 receptor (IL-6Rα), which interacts with IL-6 to initiate signaling. + - The trans-signaling pathway, which involves the soluble IL-6 receptor (sIL-6Rα). In this pathway, the IL-6/sIL-6Rα complex can bind to the gp130 membrane-bound receptor to form an active signaling complex that initiates further downstream effects, such as the activation of Janus kinase (Jak) family proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation. -3. **Interactions with Other Molecules:** - - IL-6 interacts with IL-6Rα and gp130 to form a receptor complex that activates intracellular signaling pathways. - - It leads to the phosphorylation of Janus kinase (Jak) family proteins and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3), which are critical for transmitting the signal inside the cell. +3. **Interactions with Other Molecules**: IL-6 interacts with both its membrane-bound and soluble receptors (IL-6Rα and sIL-6Rα) to form complexes that recruit gp130, leading to signal transduction. The interaction with gp130 is crucial as it leads to the formation of an active hexameric receptor complex which drives further signaling processes. -4. **Importance in the Biological System Being Modeled:** - - In the context of Crohn's disease, IL-6 contributes to enhanced T-cell survival and resistance to apoptosis in the lamina propria, along with elevated chemokine secretion. This makes it a significant player in the disease's pathology. - - The study of IL-6 and its pathways is crucial in understanding its role in diseases such as Crohn's disease and rheumatoid arthritis, and in developing therapeutic interventions targeting IL-6 signaling. +4. **Importance in Biological Systems**: IL-6 is particularly significant in the pathology of inflammatory diseases, such as Crohn's disease. It contributes to enhanced T-cell survival and apoptosis resistance, as well as elevated chemokine secretion in the intestinal mucosa and peripheral blood. This makes IL-6 signaling a critical target for therapeutic interventions in such conditions. -Overall, IL-6 is an important cytokine with significant roles in immune response and inflammation, making it a key target for research in immune-mediated diseases." -mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83,R_IL6,R_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, there is no specific mention of a species named 'R_IL6'. However, based on the context and related molecules mentioned, it is possible to infer some insights into what 'R_IL6' might relate to. +In summary, IL-6 is a multifunctional cytokine with essential roles in immune regulation and inflammatory responses, especially relevant to conditions like Crohn’s disease. Its ability to signal through multiple pathways and interact with various molecular complexes underscores its importance in maintaining immune homeostasis and its potential as a therapeutic target." +mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83,R_IL6,R_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The provided context does not explicitly detail the species 'R_IL6' with the specified ID. However, based on the information present and general biological knowledge, 'R_IL6' could potentially represent a receptor or related component involved in the Interleukin-6 (IL-6) signaling pathway. -### Biological Function: -- **IL-6:** IL-6 (Interleukin-6) is a cytokine involved in immune response, inflammation, and hematopoiesis. It plays a significant role in the body's defense mechanisms and is implicated in various diseases when dysregulated. +### General Knowledge Inference for 'R_IL6': +1. **Biological Function**: + - IL-6 is a cytokine that plays a critical role in immune response, inflammation, and hematopoiesis. It typically signals through a receptor complex that may include the IL-6 receptor (IL-6R) and a signal transducer such as gp130. + - The designation 'R_IL6' suggests it may be an IL-6 receptor component, involved in binding IL-6 and initiating downstream signaling pathways. -### Role in Pathways: -- **IL-6 Signaling Pathway:** This pathway involves the binding of IL-6 to its receptor, IL-6R, and generally leads to the activation of JAK/STAT signaling pathways. This signaling can induce transcription and various immune responses. +2. **Role in Pathways**: + - IL-6 signaling involves the activation of the Janus kinase (Jak) and Signal Transducer and Activator of Transcription 3 (STAT3) pathway. Binding of IL-6 to its receptor complex activates these pathways, leading to the transcription of genes involved in inflammatory and immune responses. + - The context also mentions ""Classical"" and ""Trans"" pathways, suggesting classical signaling involves membrane-bound IL-6R, while trans-signaling involves soluble IL-6R (sIL-6R). -### Interactions with Other Molecules: -- **IL-6R and sIL-6R (soluble IL-6 receptor):** The IL-6 signaling requires the complex formation of IL-6 with its receptor IL-6R, including its soluble form sIL-6R. This complex can further bind to another molecule, gp130 (glycoprotein 130), which is necessary for signal transduction. -- **STAT3:** The context mentions pSTAT3 signaling, indicating that IL-6 signaling involves phosphorylation of STAT3, a transcription factor that mediates various gene expressions in response to IL-6. +3. **Interactions with Other Molecules**: + - IL-6 interacts with both its membrane-bound and soluble forms of IL-6R, which facilitates different signaling outcomes. + - Interaction with sIL-6R allows IL-6 to signal in cells that do not express membrane-bound IL-6R by associating with the ubiquitously expressed signal transducer, gp130. + - The term 'R_IL6' within a complex might specifically denote its interaction with these molecules in such pathways. -### Importance in the Biological System Being Modeled: -- **Regulation and Modeling:** IL-6 is involved in the regulation of immune processes, and its signaling is crucial in understanding conditions like Crohn's disease or rheumatoid arthritis. The context mentions modeling efforts and pharmacokinetic analyses suggesting a focus on IL-6 and its receptor interactions. -- **Treatment Implications:** The modeling discussed, such as the dose-response characteristics, indicates IL-6's importance in therapeutic frameworks, potentially focusing on disorders with immune dysregulation. +4. **Importance in the Biological System**: + - IL-6 signaling is crucial for immune regulation and has been implicated in several inflammatory diseases such as Crohn’s disease and rheumatoid arthritis. + - Modulating IL-6 activity, often through its receptor interactions, is a therapeutic target for reducing chronic inflammation and autoimmune diseases. -### Potential Inference for 'R_IL6': -- While there is no direct mention of 'R_IL6', it could potentially refer to a variant, receptor, or complex of IL-6 involved in signaling pathways. It might be modeled similarly in studies related to immune regulation or therapeutic targeting. Given the context, it is likely associated with IL-6's complex pathways and interactions within the immune system. +Overall, while the specific role of 'R_IL6' is not detailed in the provided text, understanding its potential place within IL-6 signaling pathways offers insights into its biological significance and therapeutic relevance." +mw0eb6c959_d408_45a0_a450_928b8c5876bb,Ractive,Ractive,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The provided context does not contain specific information about the species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). The text focuses primarily on the IL-6 signaling pathway, its associated components, and the effects of targeting this pathway with therapeutic antibodies such as anti-IL-6 and anti-IL-6Rα, particularly in the context of autoimmune diseases like Crohn's Disease and rheumatoid arthritis. -In summary, 'R_IL6' could be a component related to IL-6 signaling, likely significant in immune system modeling and therapeutic interventions." -mw0eb6c959_d408_45a0_a450_928b8c5876bb,Ractive,Ractive,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided does not include specific information about a species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). However, I can provide inferential information based on the general context described, which involves IL-6 signaling and therapeutic interventions in conditions like rheumatoid arthritis and Crohn’s disease. +Since there is no direct mention of 'Ractive' in the context, we can infer its nature based on the general themes discussed: -1. **Biological Function:** - - Although 'Ractive' is not directly mentioned, within the context of an immune regulation framework, it could be hypothesized that 'Ractive' might represent a molecule involved in the immune response or signal transduction, perhaps similar to interleukins or receptors. +1. **Biological Function & Role in Pathways**: Given the context's focus on the IL-6 pathway, Ractive might be hypothesized as a molecule related to cytokine signaling, possibly a receptor, a part of a signaling cascade, or even an associated regulatory protein modulating immune responses. -2. **Role in Pathways:** - - Considering the IL-6 signaling pathway is a focal point of the study, 'Ractive' might play a role similar to elements of the IL-6 signaling cascade. This could involve participation in cytokine signaling or acting as a receptor or receptor complex, similar to IL-6 or its soluble receptor counterparts. +2. **Interactions with Other Molecules**: In a systems biology model of immune regulation, Ractive might interact with cytokines (like IL-6), receptors (such as IL-6Rα), or downstream signaling molecules (e.g., STAT proteins). Its interactions would be crucial for understanding the dynamics of the immune response. -3. **Interactions with Other Molecules:** - - 'Ractive' might engage in interactions akin to the IL-6 and its soluble receptor interactions. Such molecules often form complexes that could be potential targets for therapeutic antibodies or other modulators, a common approach in autoimmune conditions like those discussed. +3. **Importance in the Biological System**: If Ractive is indeed involved in the IL-6 mediated pathway, it would be important for modulating immune responses, potentially influencing inflammation and immune system activity, which are critical in conditions like Crohn’s Disease. -4. **Importance in the Biological System:** - - If 'Ractive' partakes in a pathway analogous to IL-6 signaling, it could be crucial in mediating inflammatory responses, playing a part in disease progression or resolution, and thus presenting itself as a possible target for therapeutic intervention. +In the absence of context-specific information about 'Ractive', it is important to consult the original source documents or related scientific literature for precise insights into this species’ characteristics and role within the biological system being modeled." +mw42054cd7_17af_46da_970c_7f99151906ad,STAT3,STAT3,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context and general knowledge, here is the background information about STAT3: + +### General Background on STAT3: +STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that is pivotal in transmitting signals from the cell surface to the nucleus. It is part of the STAT protein family and is involved in cellular processes such as cell growth and apoptosis. + +### Biological Function: +STAT3 is primarily activated through phosphorylation—a process in which a phosphate group is added, often leading to a functional change of the protein. Once phosphorylated (pSTAT3), it dimerizes and translocates to the nucleus where it can influence the expression of a variety of genes. + +### Role in Pathways: +STAT3 is a critical component of the JAK-STAT signaling pathway, which is a chain of interactions between proteins in a cell, and is also involved in mediating responses to cytokines and growth factors. In this context, it appears specifically related to IL-6 signaling. IL-6 is a cytokine that can induce the phosphorylation of STAT3, leading to its activation and subsequent gene transcription that drives processes like differentiation of lymphocytes and expression of acute-phase proteins such as C-reactive protein (CRP). -Without specific information on 'Ractive' from the text, these interpretations are speculative and should be considered within the broader context of known signaling pathways and therapeutic targets discussed in the study." -mw42054cd7_17af_46da_970c_7f99151906ad,STAT3,STAT3,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context and general knowledge: +### Interactions with Other Molecules: +STAT3 interacts with various molecules primarily through the phosphorylation process. It is closely tied to components like gp130 and sIL-6R in the IL-6 signaling cascade. In response to IL-6, the receptor complex that includes IL-6Rα and gp130 becomes activated, leading to JAK activation and subsequent phosphorylation of STAT3. -### Biological Function of STAT3 -STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor activated by phosphorylation. It is a key player in transmitting signals from various cytokines and growth factors to the cell nucleus, where it modifies gene expression. STAT3 is critical for regulating numerous biological processes, including cell growth, apoptosis, and immune response. +### Importance in Biological Model: +Within the context of the provided information, STAT3 plays a significant role in diseases such as Crohn's disease, where its phosphorylated form, pSTAT3, has been observed in colon biopsies. This suggests that STAT3 might be central to inflammatory signaling pathways that underpin certain diseases, making it a potential target for therapeutic interventions. -### Role in Pathways -STAT3 is involved in the JAK-STAT signaling pathway. Upon activation, typically by cytokines such as IL-6, STAT3 is phosphorylated by associated Janus kinases (JAKs), dimerizes, and translocates to the nucleus. In this context, STAT3 appears integral to the IL-6 signaling pathway, which is involved in various cellular responses, including inflammation, immune function, and acute-phase reactions. +This inferred understanding aligns with its general role in bodily immunity and inflammation, highlighting its potential implications in both research and clinical settings relevant to cytokine signaling and immune response regulation." +mw39c2e431_fdc3_4964_be29_6ca856620b1b,pSTAT3,pSTAT3,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context and general knowledge, here's an overview of pSTAT3: -### Interactions with Other Molecules -Within the IL-6 signaling pathway, STAT3 interacts with molecules such as the IL-6 receptor (IL-6R), gp130, and soluble forms of these receptors (sIL-6R and sgp130). The phosphorylation of STAT3 (pSTAT3) indicates its activation and subsequent transcriptional regulation of target genes. +### Biological Function: +- pSTAT3, or phosphorylated STAT3, is part of the STAT (Signal Transducer and Activator of Transcription) family of transcription factors. These proteins are crucial for relaying information from extracellular signals to the cell nucleus, where they influence gene expression. +- Upon activation, STAT3 becomes phosphorylated, hence pSTAT3, which allows it to dimerize (pair with another STAT3 molecule), translocate to the nucleus, and bind to DNA, promoting the transcription of target genes. -### Importance in Biological Systems -STAT3 plays a significant role in mediating the effects of cytokines like IL-6, which are crucial in immune responses and inflammation. The context mentions disease models such as Crohn's disease, where increased activation of STAT3 (pSTAT3) in tissues is noted, highlighting its potential role in the disease's inflammatory processes. This suggests that STAT3's regulation is pivotal in understanding and developing therapeutic approaches for immune and inflammatory disorders. +### Role in Pathways: +- pSTAT3 is instrumental in the IL-6 signaling pathway. IL-6 is a cytokine that, upon binding to its receptors, activates the Janus kinase (Jak) pathway, which in turn phosphorylates STAT3. +- The context describes a trans-signaling pathway involving IL-6 and its soluble receptor sIL-6Rα, with pSTAT3 being a downstream effector of this pathway. +- This pathway is crucial for various cellular responses, including differentiation, survival, and proliferation, especially in immune and inflammatory responses. -In summary, STAT3 is a central molecule in cytokine signaling pathways that influence immune function and inflammation, making it a critical target for studying diseases characterized by dysregulated immune responses, such as Crohn's disease." -mw39c2e431_fdc3_4964_be29_6ca856620b1b,pSTAT3,pSTAT3,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided mainly revolves around the IL-6 signaling pathway and its components, such as IL-6Rα, gp130, sIL-6Rα, sgp130, and CRP, with sporadic mentions of STAT3 and pSTAT3. Here’s a summary focused on pSTAT3 based on the document and broader biological knowledge: +### Interactions with Other Molecules: +- The phosphorylation of STAT3 is a result of interactions with upstream kinases like Jak, following cytokine receptor activation (e.g., by IL-6/sIL-6Rα). +- pSTAT3 is known to interact with various co-factors and DNA sequences to regulate the expression of genes involved in inflammation and immune responses. +- It is hinted that pSTAT3 levels are elevated in inflammatory conditions like Crohn’s disease, indicating interactions with molecules or pathways involved in inflammation. -### pSTAT3 Biological Function -- **pSTAT3** refers to the phosphorylated form of STAT3 (Signal Transducer and Activator of Transcription 3). -- STAT3 is a transcription factor activated in response to cytokines like IL-6. -- When phosphorylated, STAT3 dimerizes and translocates to the nucleus to regulate the expression of target genes. +### Importance in the Biological System: +- pSTAT3 is a critical mediator in the context of inflammatory diseases, such as Crohn’s disease, where its increased levels in colon biopsies suggest a role in the pathogenesis or progression of these diseases. +- By regulating gene expression in response to cytokine signaling, STAT3, especially in its phosphorylated form, is important for maintaining appropriate immune responses and cellular homeostasis. +- Its role extends beyond normal physiology to pathophysiological conditions, where its dysregulation is often linked to chronic inflammatory states, autoimmune disorders, and even cancers. + +In summary, pSTAT3 is a pivotal molecule within the IL-6 cytokine signaling pathway, acting as a key transcriptional regulator in immune and inflammatory responses. Its heightened activity is associated with pathological conditions, highlighting its importance as a potential therapeutic target in such diseases." +mwd5313618_89eb_4c8c_bc82_66f10f966349,"CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",CRP,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, here is the background information about the species 'CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)': -### Role in Pathways -- **IL-6 Signaling**: pSTAT3 is a critical component of the IL-6 signaling pathway. The binding of IL-6 to its receptor leads to the activation of the JAK kinases, which in turn phosphorylate STAT3. -- **Gene Expression**: pSTAT3 influences the transcription of various genes involved in immune responses, cell survival, and proliferation. +1. **Biological Function**: CRP, or C-reactive protein, is a biomarker of inflammation in the body. It is produced by the liver in response to inflammation and its levels increase in the bloodstream during inflammatory processes. -### Interactions with Other Molecules -- **IL-6 and sIL-6Rα**: The context describes the significance of trans-signaling mediated by IL-6 and its soluble receptor forms, which lead to STAT3 phosphorylation. -- **gp130**: This coreceptor is crucial for the activation of STAT3. It binds the IL-6/sIL-6R complex leading to STAT3 phosphorylation. -- **CRP and other gene products**: The activation of STAT3 can influence the expression of C-reactive protein and other acute-phase proteins. +2. **Role in Pathways**: CRP is primarily associated with the body's immune response to inflammation. It is part of the acute phase response, which is a rapid systemic response to injury, infection, or other inflammatory stimuli. The context suggests that CRP is being used in a model to evaluate inflammation levels, particularly in relation to Crohn’s disease and the effects of anti-inflammatory drugs like tocilizumab. -### Importance in the Biological System -- **Pathological Conditions**: The document mentions increased pSTAT3 levels in colon biopsies in the context of Crohn’s disease, suggesting its role in inflammatory bowel diseases. -- **Biological Significance**: Being a part of the IL-6 signaling pathway, pSTAT3 is important in mediating immune responses and might have implications in various diseases due to dysregulated cytokine signaling. +3. **Interactions with Other Molecules**: CRP interacts with various components of the immune system. In the context of the document, CRP levels are used to assess the effectiveness of inhibiting IL-6 signaling—a cytokine involved in inflammation by targeting IL-6 or its receptors. Thus, CRP serves as an indicator for the efficacy of this anti-inflammatory strategy. -In summary, pSTAT3 is a pivotal signaling molecule involved in transcriptional regulation, primarily within the IL-6-mediated pathway. Its phosphorylation status determines its activity, which can impact various biological processes and contributes to disease states such as inflammatory bowel disease." -mwd5313618_89eb_4c8c_bc82_66f10f966349,"CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",CRP,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species referred to as ""CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)"" in the provided context likely represents C-reactive protein (CRP), based on the common abbreviation for C-reactive protein. Here is a summary of the relevant background information regarding CRP: +4. **Importance in the Biological System Being Modeled**: In the model described, CRP is a critical marker used to validate and predict the outcomes of drug treatments aimed at reducing inflammation, such as those used in Crohn's disease. The model uses CRP as a metric to evaluate the suppression of inflammation due to the therapeutic inhibition of IL-6 signaling pathways. + +In summary, CRP is an important inflammatory marker used in the modeling of immune response and drug efficacy in inflammatory diseases, particularly for evaluating interventions targeting IL-6 signaling." +mw2e464cf3_a09c_4b7c_9f3c_06720016a48e,"sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"From the context provided, it seems that the specific species 'sR' (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) is not directly mentioned or detailed. Thus, I will infer its possible role based on the general context involving related biological components. 1. **Biological Function:** - - CRP is an acute-phase protein produced by the liver in response to inflammation. Its primary function is to bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system via C1q. + - Given the surrounding context of interleukin 6 (IL-6), it is likely that 'sR' refers to a soluble receptor, potentially the soluble IL-6 receptor (sIL-6R). Soluble receptors often function to sequester ligands or modulate signaling pathways by facilitating ligand interaction with cell surface receptors. 2. **Role in Pathways:** - - CRP is often used as a clinical biomarker for inflammation. It plays a significant role in the pathway of immune response, particularly in recognizing and promoting the clearance of pathogens and damaged cells, thereby serving as a marker of inflammation and immune system activation. - - In the context of the simulation model discussed, changes in CRP levels can indicate the effectiveness of drug treatments targeting the IL-6 signaling pathway, as CRP levels are a downstream effect of cytokine signaling, particularly IL-6. + - 'sR', if it represents sIL-6R, participates in the IL-6 signaling pathways. IL-6 can bind to sIL-6R, forming a complex that further associates with membrane-bound gp130, leading to activation of intracellular signaling pathways such as the JAK/STAT pathway. This pathway is involved in inflammation and the regulation of the immune response. 3. **Interactions with Other Molecules:** - - CRP interacts with various components of the immune system such as the complement system. It works closely with interleukin-6 (IL-6), as IL-6 is a major inducer of CRP synthesis in the liver. - - The context mentions interactions with drugs such as anti-IL-6Rα antibodies, which suggests that CRP levels are used to measure the impact of these treatments on inflammation levels in diseases like Crohn's disease. + - 'sR' forms part of the IL-6/sIL-6R complex interacting with gp130, a common receptor subunit involved in IL-6 family cytokine signaling. This complex formation enhances signaling across various tissues, especially when the IL-6 concentration is limited, as seen from the content discussing IL-6 and sgp130 concentrations. 4. **Importance in the Biological System Being Modeled:** - - Within the modeled system (as described in the context), CRP serves as a critical marker for inflammation, allowing researchers to predict the impact of various treatment strategies on inflammatory diseases like Crohn's disease. - - The model’s ability to predict changes in CRP levels helps in studying the effects of perturbations through different therapeutic approaches aimed at inhibiting the IL-6 signaling pathway. + - If 'sR' represents a soluble receptor interacting with IL-6, it plays a crucial role in modulating IL-6's effects, potentially affecting processes like acute-phase responses, immune function, and inflammation. The model suggests that perturbations in components like sgp130 have minor effects due to concentration differences, implying that the effective modulation of signaling depends heavily on components like sR/sIL-6R and IL-6 interactions. -Overall, CRP is an important indicator of inflammation and is crucial in the validation and assessment of disease models involving inflammatory processes, such as those involving IL-6 signaling." -mw2e464cf3_a09c_4b7c_9f3c_06720016a48e,"sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, specific information about the species 'sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned. However, inferring from the general context of the documents, which involve molecular interactions and pathways related to the IL-6 signaling system, the following insights can be suggested: +In summary, while 'sR' is not explicitly described, it might denote a molecule like the soluble IL-6 receptor within the context of IL-6 signaling pathways, influencing inflammatory and immune responses." +mw36ea78c1_ed71_4def_96d3_857a442d7195,CRPExtracellular,CRPExtracellular,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, it seems that specific information about the species 'CRPExtracellular' (ID: mw36ea78c1_ed71_4def_96d3_857a442d7195) within the context of mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e is not explicitly detailed. However, we can infer some information based on the general role of C-reactive protein (CRP) within biological systems and its mention in the context. -1. **Biological Function**: - - The 'sR' component is likely a part of the IL-6 signaling pathway. In similar contexts, 'sR' often denotes soluble receptors. Soluble receptors can modulate the activity of their respective cytokines or hormones by binding to them and altering their bioavailability or impacting downstream signaling pathways. +1. **Biological Function**: CRP, or C-reactive protein, is a substance produced by the liver in response to inflammation. Its primary function is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via the C1Q complex, thus playing an important role in the body's immune response by enhancing the ability to clear pathogens and damaged cells. -2. **Role in Pathways**: - - Considering the IL-6 pathway is mentioned, the 'sR' species might function in the classical signaling or trans-signaling pathways of IL-6. In these pathways, soluble receptors either enhance or inhibit signal transduction, impacting gene expression mediated by factors like STAT3. +2. **Role in Pathways**: CRP is typically involved in the acute phase response to inflammation. Its production increases in response to pro-inflammatory cytokines like interleukin-6 (IL-6), as indicated by the context mentioning IL-6 and CRP in relation to various treatments aiming to modulate inflammation pathways. -3. **Interactions with Other Molecules**: - - The context suggests interaction with the IL-6 cytokine, as soluble IL-6 receptors (e.g., sIL-6R) bind IL-6, forming a complex (IL-6:sR) that may interact with other receptor components, such as gp130, to elicit a cellular response. These interactions are crucial for regulating inflammatory responses and immune function. +3. **Interactions with Other Molecules**: The interaction between CRP and IL-6 is highlighted, with IL-6 being a key cytokine that stimulates the production of CRP. The context also discusses various treatment strategies that involve targeting IL-6 or its receptors to reduce inflammation and subsequently decrease CRP levels, demonstrating CRP's role as a marker for inflammatory activity and the effectiveness of anti-inflammatory treatments. -4. **Importance in the Biological System Being Modeled**: - - Soluble receptors are significant in maintaining homeostasis and regulating the intensity of cytokine signaling. The modeling aspect suggests that understanding the dynamic balance of these components (like sgp130, mentioned in the document) is crucial for accurately predicting system behavior under various conditions and treatments, especially targeting IL-6 or its receptors. +4. **Importance in the Biological System Being Modeled**: The context suggests that CRP is used as a biomarker for inflammation in Crohn’s disease, and its levels are used to monitor the effectiveness of treatment strategies that target IL-6 signaling. Therefore, CRP is a key output in the model being discussed, representing the systemic inflammatory response and providing feedback on the effectiveness of therapeutic interventions. -In summary, 'sR' in this context is likely a soluble receptor involved in the IL-6 signaling pathway, influencing immune responses by modulating cytokine availability and activity." -mw36ea78c1_ed71_4def_96d3_857a442d7195,CRPExtracellular,CRPExtracellular,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species named 'CRPExtracellular' likely refers to the extracellular form of C-reactive protein (CRP), a well-known biomarker and acute-phase protein in various biological systems, particularly in the context of inflammation. +In conclusion, while specific details about the species 'CRPExtracellular' in the mentioned context are not given, its role as a marker of inflammation and its regulation through pathways involving IL-6 are central to the model's focus on understanding and predicting the outcomes of therapeutic interventions in inflammatory conditions like Crohn’s disease." +mw147d30ec_478e_4090_b496_128a131d29eb,"sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sgp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, the species labeled as 'sgp130' (associated with ID: mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e) seems to be a fusion protein designed to interact with components involved in IL-6 signaling pathways. Here's a summary of its relevant aspects: -### Biological Function -C-reactive protein (CRP) is produced by the liver in response to inflammation. It is an acute-phase protein that plays a critical role in the host's defense mechanism. CRP is part of the innate immune system as it binds to the surface of dead or dying cells and certain bacteria to activate the complement system, promoting phagocytosis by macrophages. +- **Biological Function:** + - sgp130 functions as an inhibitor of IL-6 trans-signaling. It is a fusion protein that combines the extracellular portion of gp130 with the Fc region of human IgG1, termed sgp130Fc. This modification allows sgp130 to bind to the IL-6/sIL-6Rα complex. -### Role in Pathways -In the context of the provided documents, CRP is linked to the IL-6 signaling pathway. IL-6 is a cytokine that stimulates the production of CRP in the liver. The IL-6 mediated pathway contributes to inflammatory responses, and CRP serves as a downstream marker for inflammation. The model mentioned explores strategies to treat Crohn's disease by inhibiting IL-6 signaling, which suggests a modulation of CRP levels. +- **Role in Pathways:** + - It is involved in the IL-6 trans-signaling pathway. IL-6 is a cytokine that plays a crucial role in immune response and inflammation. The trans-signaling pathway involves the binding of IL-6 to a soluble receptor sIL-6Rα, which then associates with gp130 to signal. -### Interactions with Other Molecules -CRP interacts with various molecules and systems in the body: -- It binds to phosphocholine on the surface of dead cells and some types of bacteria. -- CRP activates the complement system, which enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells. -- CRP levels are used to assess the extent of inflammation in response to stimuli like IL-6, another cytokine involved in the body's inflammatory response. +- **Interactions with Other Molecules:** + - sgp130 interacts specifically with the IL-6/sIL-6Rα complex. The context suggests that sgp130 binds this complex with similar affinity to natural gp130, aiming to inhibit downstream signaling events such as CRP (C-reactive protein) and pSTAT3 production in the gut. -### Importance in the Biological System Being Modeled -In the biological model presented in the documents, CRP serves as a critical biomarker to evaluate the efficacy of therapeutic strategies targeting IL-6 signaling in inflammatory diseases like Crohn's disease. The documents emphasize the model's capacity to predict the response of CRP levels to different treatment strategies, validating the trained model against clinical trial data. Suppression of CRP is an indicator of effective inhibition of inflammation, showcasing the importance of CRP measurement in assessing the success of interventions aimed at controlling inflammatory pathways. +- **Importance in the Biological System:** + - Despite its designed purpose, simulations and sensitivity analyses indicate that sgp130 (as sgp130Fc) has relatively low impact on the biological system being modeled, particularly when used as a therapeutic agent for conditions like Crohn’s disease. Its effectiveness is noted only at very high and frequent doses due to the high baseline levels of sgp130 naturally present, in contrast to the low concentration of IL-6. -In summary, CRPExtracellular represents the extracellular C-reactive protein operating as a biomarker for inflammation, influenced by IL-6 signaling pathways, and significant in evaluating treatment efficacy for diseases characterized by chronic inflammation." -mw147d30ec_478e_4090_b496_128a131d29eb,"sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sgp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species referred to as 'sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' appears to be a protein known as sgp130 located in a specific biological context (ID: mw147d30ec_478e_4090_b496_128a131d29eb). Here is a summary of the relevant background information: +In summary, sgp130 is primarily modeled to inhibit IL-6 trans-signaling but poses challenges as a therapeutic due to its excess presence compared to IL-6, limiting its potential impact on the system without large dosage increases." +mwab41493c_6349_45f1_a226_3030cfed0e06,"sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR_IL6_sgp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, specific mentions of the species named 'sR_IL6_sgp130' (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) are not directly available. However, we can infer its nature and potential role based on the information about similar molecules provided in the document. -1. **Biological Function**: - sgp130 is a soluble form of gp130, which is a component of the IL-6 receptor complex. sgp130 acts by binding to the IL-6/sIL-6Rα complex, thereby inhibiting IL-6 trans-signaling. This function is crucial as IL-6 trans-signaling is associated with various inflammatory and autoimmune conditions. +1. **Biological Function**: The context discusses sgp130, which is known to be a soluble form of the gp130 receptor. These soluble receptors, like sgp130, are known to inhibit IL-6 trans-signaling. In general, soluble receptors can bind cytokines or cytokine complexes in the extracellular environment, preventing them from triggering cell surface receptors and subsequent intracellular signaling cascades. -2. **Role in Pathways**: - sgp130 plays a role in the IL-6 signaling pathway by inhibiting the formation of active signaling complexes. This modulation of the pathway can potentially reduce inflammatory responses mediated through IL-6 trans-signaling. +2. **Role in Pathways**: The sgp130 serves as an inhibitor in the IL-6 signaling pathway, particularly in IL-6 trans-signaling. This pathway is involved in various inflammatory and immune processes. By inhibiting this pathway, sgp130 could potentially reduce inflammatory responses, which is particularly relevant in conditions like Crohn’s disease, as mentioned in the context. -3. **Interactions with Other Molecules**: - sgp130 interacts specifically with the complex formed by IL-6 and its soluble receptor sIL-6Rα. By binding to this complex, sgp130 prevents the subsequent interaction with the membrane-bound gp130, effectively blocking signal transduction. +3. **Interactions with Other Molecules**: The sgp130 binds to the IL-6/sIL-6Rα complex. This specific interaction is crucial for its role as an inhibitor in the pathway. It prevents the IL-6 complex from interacting with membrane-bound gp130, thus blocking downstream signaling events. -4. **Importance in the Biological System Being Modeled**: - In the context of therapeutic applications, particularly for conditions such as Crohn's disease, sgp130 is evaluated for its potential use in inhibiting inflammatory signaling. Despite being present in large concentrations compared to IL-6, sensitivity analyses suggest that the therapeutic effectiveness of sgp130-based interventions may require very high doses due to its minimal impact on overall system dynamics at typical concentrations. This is because sgp130 naturally exists in excess relative to IL-6, limiting its impact when used in moderate amounts. +4. **Importance in the Biological System Being Modeled**: In the biological system modeled, sgp130 appears to represent a regulatory component that modulates the IL-6 signaling pathway. Its presence in high baseline levels as compared to free IL-6 indicates a natural buffering or regulatory role in maintaining homeostasis in the signaling environment. It suggests that significant therapeutic modulation (e.g., large doses of sgp130Fc) would be needed to observe pronounced effects. -5. **Relevance in Systems Biology Model**: - The systems biology model suggests that while sgp130 has a role, its overall impact on key output parameters (such as CRP levels) is limited unless used in substantial amounts. It highlights the need for potentially better therapeutic targets like IL-6 and sIL-6Rα, where alterations could more significantly affect system outputs. +While specific details about 'sR_IL6_sgp130' (#2) are not available, the understanding of sgp130's role in IL-6 trans-signaling and its functional characterization can be reasonably extrapolated to gain insights into this species' potential biological importance." +mwf405687b_7401_44ec_a0d6_4a2b35c13e8a,"Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab_sR,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided does not contain specific information about the biological species or molecule named 'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' or its ID 'mwf405687b_7401_44ec_a0d6_4a2b35c13e8a'. Given the lack of direct details in the documents, I can infer potential characteristics of 'Ab_sR' based on common biological concepts and patterns discussed in similar contexts. -Overall, sgp130 serves a regulatory function in IL-6 mediated signaling, highlighting its role in inflammatory pathways but with suggested limitations for therapeutic application based on the systems biology model being considered." -mwab41493c_6349_45f1_a226_3030cfed0e06,"sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR_IL6_sgp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, the species 'sR_IL6_sgp130', identified by the ID mwab41493c_6349_45f1_a226_3030cfed0e06, appears to be related to a fusion protein that plays a role in inhibiting IL-6 trans-signaling pathways. This fusion protein, popularly referred to as sgp130Fc, combines the extracellular portion of glycoprotein 130 (gp130) with the Fc region of human IgG1. +1. **Biological Function**: Given the use of ""Ab"" in the name, 'Ab_sR' may refer to an antibody-related species, possibly a soluble receptor (sR) or an antibody-receptor complex. In many biological systems, antibodies play crucial roles in immune responses, binding to specific antigens to neutralize them or mark them for destruction by other immune cells. -**Biological Function:** -sR_IL6_sgp130 acts to bind specifically to the IL-6/sIL-6Rα complex, which is pivotal in mediating IL-6 trans-signaling. By binding to this complex, it effectively prevents the signaling process that would typically activate downstream pathways, such as the phosphorylation of STAT3 (pSTAT3) and subsequent gene transcription. +2. **Role in Pathways**: In the context of systems biology models that often study signaling and immune pathways, 'Ab_sR' may be involved in modulating signaling cascades. Since the documents mention the IL-6/sIL-6Rα complex, 'Ab_sR' might participate in pathways related to cytokine signaling, such as the interleukin-6 (IL-6) pathway, which is crucial in inflammation and immune regulation. -**Role in Pathways:** -Its primary role resides in the inhibition of IL-6 trans-signaling, which is critical in the context of inflammatory responses and diseases like Crohn’s disease. The simulations and models cited suggest that this species is involved in modifying the dose-response relationship of certain therapeutic interventions, leading to outcomes like CRP suppression. +3. **Interactions with Other Molecules**: Given the similarities to components like IL-6 and sIL-6Rα, 'Ab_sR' may interact with these molecules either as a part of a complex or influence their activity. For instance, antibodies or their fragments (like those potentially represented by 'Ab_sR') can bind to cytokines or their receptors, affecting the downstream signaling events. -**Interactions with Other Molecules:** -sR_IL6_sgp130 interacts predominantly with the IL-6/sIL-6Rα complex. The sgp130 component has a high affinity for this complex, which is a major interaction through which it achieves its inhibitory functions. +4. **Importance in the Biological System Being Modeled**: Systems biology models often explore the dynamics and regulation of complex biochemical networks. If 'Ab_sR' is involved in cytokine-receptor interactions, it can be important in modulating inflammatory responses or immune system function, potentially making it a target for therapeutic interventions in diseases characterized by inflammation or immune dysfunction. -**Importance in the Biological System Being Modeled:** -In the system, while sR_IL6_sgp130 is present in high baseline levels and exerts limited effects on steady-state system dynamics due to its excess relative to free IL-6 concentrations, it remains a pivotal molecule for therapeutic applications. Its primary importance lies in its use as a potential therapeutic intervention, especially considered for conditions with elevated IL-6 trans-signaling, requiring very high and frequent doses to be effective due to its baseline levels. +To summarize, while 'Ab_sR' is not directly described in the context provided, it is likely associated with antibody or receptor functions within signaling or immune pathways similar to those of IL-6/sIL-6Rα in the documents referenced. If additional data is available, it could help refine or confirm these inferences." +mw3667a5e1_02c9_44a0_acb4_b0431faa822d,"Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided does not offer any specific information about the species or molecule identified as 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' within the document. However, based on the excerpts, it is possible to infer the following general insights regarding similar biological components: -This summary indicates that sR_IL6_sgp130 is critical in the context of therapies aiming to modulate IL-6 signaling pathways, providing insights into the need for precise dosing strategies to achieve therapeutic benefits." -mwf405687b_7401_44ec_a0d6_4a2b35c13e8a,"Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab_sR,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, no specific information about the species named 'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' was found in the excerpts from the document. However, I can infer some potential characteristics and roles it might have based on general biological knowledge and the information typically associated with similar components. +1. **Biological Function**: The molecule labeled 'Ab' is likely an antibody, which are proteins used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. In this context, 'Ab' might refer to an antibody targeting a particular biological pathway or molecule. -1. **Biological Function**: Generally, ""Ab"" in a biological context often refers to antibodies. If 'Ab_sR' is indeed an antibody or related to antibody activity, its function could be to bind to specific antigens, perhaps part of a signaling pathway or immune response mechanism. +2. **Role in Pathways**: Antibodies are typically involved in immune response pathways. The document mentions interactions that involve the cytokine IL-6 and its receptor, IL-6Rα. It is possible that 'Ab' could be an antibody aimed at either IL-6 or IL-6Rα, or their complex, to modulate immune responses. -2. **Role in Pathways**: The context mentions IL-6 and its receptor interactions, which are part of immune signaling pathways. If 'Ab_sR' is interacting with such pathways, it could be modulating or inhibiting specific signals, particularly in inflammatory or immune responses. +3. **Interactions with Other Molecules**: The document excerpt references the targeting of IL-6 or its receptor, sIL-6Rα. These molecules play roles in inflammatory processes, indicating that 'Ab' might interact with these molecules and potentially be used to suppress inflammation or other immune responses. -3. **Interactions with Other Molecules**: As the context heavily references IL-6, IL-6R, and associated signaling components like STAT3 and SOCS, it is plausible that 'Ab_sR' could interact with these molecules. It might bind to a receptor or signaling molecule to alter its activity. +4. **Importance in the Biological System**: Antibodies like 'Ab' are important in a biological system because they can help to precisely modulate pathways that involve cytokines like IL-6, which are crucial in inflammatory and immune responses. This suggests its relevance in therapeutic interventions, especially in conditions where regulating immune activity is necessary. -4. **Importance in the Biological System**: Assuming 'Ab_sR' is an antibody related to receptor activity, it could be crucial in modulating inflammatory responses or other cytokine-related pathways. In systems biology models, such antibodies are often used to simulate therapeutic interventions, inhibiting specific pathways to predict changes in disease states or therapeutic outcomes. +An understanding of similar antibodies, like anti-IL-6 or anti-IL-6R antibodies, typically helps in reducing inflammation and is useful in treating conditions like rheumatoid arthritis and other autoimmune diseases. -Without explicit details from the document, these inferences remain general and speculative. Further details would be needed for precise characterization." -mw3667a5e1_02c9_44a0_acb4_b0431faa822d,"Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, there isn't directly available specific information about the species named 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, we can infer its role based on general knowledge and the content present in the documents. +In conclusion, while there is no direct information about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)', it can be inferred to be an antibody with potential functions related to immune modulation, likely within pathways involving IL-6 and its receptor(s)." +mw772cbf20_3fc1_4800_ae59_77884f1ae333,Ab_R,Ab_R,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided does not specifically mention the species 'Ab_R' with the ID mw772cbf20_3fc1_4800_ae59_77884f1ae333 located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e. However, the documents discuss the use of antibodies in modulating interleukin pathways, specifically targeting IL-6 and its receptor variants. -1. **Biological Function:** 'Ab' likely refers to an antibody, given the context of medical and pharmacological studies. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. +Based on general knowledge and the context provided, Ab_R might represent an antibody related to the regulation or interaction with the IL-6 pathway or its receptors. -2. **Role in Pathways:** Antibodies are a crucial part of the immune response, often engaging in pathways related to immune regulation and inflammatory responses. Specifically, within the context, it seems to be involved in pathways targeting IL-6 or IL-6Rα, which are significant in inflammatory processes and immune system signaling, especially in conditions like inflammatory bowel diseases and other inflammatory responses. +1. **Biological Function**: If Ab_R is an antibody, its primary function might be to bind to specific targets, such as antigens or receptors like IL-6, sIL-6Rα, or the IL-6/IL-6R complex, to modulate immune responses or inflammatory pathways. -3. **Interactions with Other Molecules:** Within the context, the antibodies interact with IL-6 and sIL-6Rα (soluble IL-6 receptor alpha). These interactions are essential as they form complexes that are targets for therapeutic interventions to suppress inflammatory markers like C-reactive protein (CRP). The effectiveness of such interventions can vary based on whether IL-6 and its receptor are targeted individually or together. +2. **Role in Pathways**: An antibody resembling Ab_R in this context could be involved in reducing inflammation by blocking the interaction between IL-6 and its receptor, preventing downstream signaling and overactivation of the immune response. This could be relevant in the context of diseases with inflammatory components. -4. **Importance in the Biological System:** Antibodies, like the one inferred (potentially anti-IL-6 or similar), are important in modulating the immune response and are used in therapeutic settings to treat diseases where cytokine activity (like that of IL-6) is dysregulated. They help reduce undesirable inflammation and are thus a critical part of managing inflammatory diseases. +3. **Interactions with Other Molecules**: Ab_R might interact with proteins like IL-6, its receptors, or complexes such as IL-6/IL-6R, aiming to modulate their activity or presence in the system, leading to changed concentrations of downstream inflammatory markers such as C-reactive protein (CRP). -In summary, while specific details about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' are not provided, it is most likely a therapeutic antibody involved in pathways targeting IL-6 and its receptor, pivotal in controlling inflammation within biological systems." -mw772cbf20_3fc1_4800_ae59_77884f1ae333,Ab_R,Ab_R,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The document provided does not explicitly mention the species 'Ab_R' with the ID 'mw772cbf20_3fc1_4800_ae59_77884f1ae333.' Therefore, I will infer what 'Ab_R' might pertain to based on the general knowledge presented in the context and common biological components. +4. **Importance in the Biological System**: In the modeled biological system, such an antibody would be crucial for understanding and predicting therapeutic responses in diseases involving chronic inflammation, autoimmune conditions, or cancer. Its efficacious application could provide insights into novel therapeutic strategies. -1. **Biological Function:** - - Given that the context mentions anti-IL-6 and anti-IL-6Rα antibodies, it is plausible that 'Ab_R' could represent an antibody (Ab) related to these immune system components. +While specific information about 'Ab_R' is not available from the context, the inference aligns it with potentially important roles in immunological regulation through mechanisms of blocking or interacting with cytokine pathways, as seen in therapeutic antibodies targeting the IL-6 signaling axis." +mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf,"Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab_sR_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The provided context lacks specific information about the species identified as 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, based on general knowledge and the context concerning IL-6 and its soluble receptor sIL-6Rα, we can infer the following: -2. **Role in Pathways:** - - Antibodies targeting the IL-6/IL-6Rα pathway are involved in modulating inflammatory responses. IL-6 is a cytokine involved in immune regulation, and its receptor, IL-6Rα, can exist in both a soluble and membrane-bound form, playing roles in signaling cascades that promote inflammation. +1. **Biological Function**: The molecule 'Ab_sR_IL6' likely functions as an antibody targeting the IL-6/sIL-6R complex. IL-6 is a cytokine involved in inflammatory and immune responses, and sIL-6R is its soluble receptor form. Antibodies targeting these molecules are typically designed to modulate the immune response, particularly in diseases characterized by excessive inflammatory signaling such as Crohn’s Disease. -3. **Interactions with Other Molecules:** - - If 'Ab_R' is, in fact, an antibody similar to anti-IL-6 or anti-IL-6Rα, it would likely bind to these targets to inhibit cytokine signaling, thereby reducing inflammation. It may interact with IL-6, IL-6Rα, or both. +2. **Role in Pathways**: This antibody likely plays a role in blocking or modulating the pathway involving IL-6-mediated signaling. By binding to IL-6 and/or sIL-6R, it prevents their interaction with gp130, a co-receptor necessary for signal transduction, thereby inhibiting downstream signaling effects like the activation of STAT3 and the subsequent transcription of inflammatory genes. -4. **Importance in the Biological System Being Modeled:** - - The context of the document suggests a focus on modeling pharmacokinetics and pharmacodynamics (PK/PD) of antibodies targeting IL-6/IL-6Rα pathways, often to evaluate potential therapeutic interventions for conditions involving chronic inflammation, such as autoimmune diseases or inflammatory diseases like Crohn’s disease (CD). - - Such antibodies can serve as therapeutic agents to suppress the inflammatory response by antagonizing the IL-6 pathway, therefore reducing downstream effects like C-reactive protein (CRP) levels, which is a marker of inflammation. +3. **Interactions with Other Molecules**: The primary interaction of 'Ab_sR_IL6' would be with IL-6 and sIL-6Rα, limiting their availability to participate in inflammatory signaling. This kind of interaction is often employed to reduce levels of inflammatory mediators like C-reactive protein (CRP) in the circulation. -Conclusively, while the document does not provide direct information on 'Ab_R,' it is likely aligned with therapeutic antibodies targeting cytokine signaling pathways to control inflammation within a modeled biological framework." -mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf,"Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab_sR_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The species 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' is not directly mentioned in the provided context. However, it is possible to infer details about this species based on the context and general knowledge about similar biological components, such as sIL-6R and IL-6. +4. **Importance in the Biological System**: In the context of the document, which seems to be related to inflammatory diseases such as Crohn's Disease, the importance of 'Ab_sR_IL6' would be in its potential therapeutic application. By reducing IL-6 signaling, it could help in controlling inflammation and alleviating disease symptoms. -1. **Biological Function**: - - Since 'Ab_sR_IL6' likely refers to an antibody (Ab) targeting soluble IL-6 receptor (sIL-6R), its primary function would be to bind soluble IL-6R, potentially inhibiting its interaction with IL-6. +In summary, while specific details about 'Ab_sR_IL6' are not provided, its naming and context imply it is an antibody targeting key components of the IL-6 signaling pathway with potential significance in therapeutic interventions for inflammatory conditions." +mw7becb5fe_8da8_4285_a821_0d77ad811b62,"sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR_IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The species 'sR_IL6' (ID: mw7becb5fe_8da8_4285_a821_0d77ad811b62) located in 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5' likely refers to a soluble receptor component involved in IL-6 signaling pathways. Although the provided context does not give explicit details about 'sR_IL6', we can infer its role based on the mention of 'sIL-6R' and related IL-6 signaling pathways: -2. **Role in Pathways**: - - In immune regulation pathways, particularly those involving interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R) can form complexes with IL-6 to mediate signaling even in cells that do not express membrane-bound IL-6R. By targeting sIL-6R, the antibody could disrupt these signaling cascades, serving as a potential therapeutic strategy in diseases characterized by excessive IL-6 signaling, such as rheumatoid arthritis or Crohn’s disease. +1. **Biological Function**: 'sR_IL6' is likely a soluble form of the IL-6 receptor, similar to 'sIL-6R'. Soluble receptors often serve to modulate cytokine signaling, either by extending the half-life of the cytokine in circulation, facilitating its transport, or altering its activity. -3. **Interactions with Other Molecules**: - - Ab_sR_IL6 would primarily interact with sIL-6R, preventing it from binding to IL-6. This could impede the formation of the IL-6/sIL-6R complex, potentially reducing downstream signaling through the STAT3 pathway and other associated responses, such as C-reactive protein (CRP) production in the liver. +2. **Role in Pathways**: The context suggests that IL-6 signals through both classical and trans-signaling pathways. In the context of immune regulation and Crohn's disease, the IL-6/sIL-6Rα complex is involved in the modulation of inflammatory responses. 'sR_IL6' is expected to participate in these pathways, potentially influencing the interaction with sgp130, a natural inhibitor of the trans-signaling route. -4. **Importance in the Biological System Being Modeled**: - - In the context of a model focused on immune regulation, particularly in conditions like Crohn’s disease, targeting sIL-6R with an antibody could be critical in modulating the inflammatory response. By acting on the IL-6 signaling pathway, such an approach could help manage systemic inflammation and related symptoms. +3. **Interactions with Other Molecules**: 'sR_IL6' would interact with IL-6, forming complexes that could be sequestered by sgp130, as well as interact with factors involved in immune signaling, such as STAT3, CRP, and possibly others involved in downstream signaling and gene transcription related to immune modulation. -While there is no specific mention of 'Ab_sR_IL6' in the provided documents, understanding its potential role can be inferred based on known dynamics of IL-6, sIL-6R, and their involvement in immune and inflammatory processes." -mw7becb5fe_8da8_4285_a821_0d77ad811b62,"sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR_IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no specific mention or detailed description of a species or molecule named 'sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, we can infer information about its potential biological role based on general knowledge of similar components in the context of the document, which discusses IL-6 signaling pathways. +4. **Importance in the Biological System**: The role of such soluble receptors is crucial in modulating the availability and activity of cytokines like IL-6. They can influence the strength and duration of signaling in different compartments, vital for maintaining balance in immune responses, particularly in diseases like Crohn's where cytokine signaling can be dysregulated. -The document prominently features IL-6 (Interleukin-6) and its role in the context of immune regulation, particularly in relation to Crohn’s disease. IL-6 is a cytokine involved in inflammation and immune responses. It signals through two main pathways: classical signaling and trans-signaling. In classical signaling, IL-6 binds to its membrane-bound receptor, IL-6R, and subsequently recruits gp130, leading to the activation of downstream pathways such as the JAK/STAT pathway. In trans-signaling, IL-6 can also bind to a soluble form of its receptor, sIL-6R, allowing it to act on cells that do not express membrane-bound IL-6R. +Based on this inference, 'sR_IL6' appears to be an important modulator within the IL-6 signaling network potentially involved in regulatory mechanisms relevant to inflammation and immune response in the context of Crohn’s disease." +mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca,"gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",gp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, the species 'gp130' is involved in the interleukin-6 (IL-6) signaling pathway. Gp130 plays a crucial role as a signal transducer for the IL-6 family of cytokines. It forms a complex with the IL-6/IL-6 receptor (IL-6R) to propagate intracellular signaling leading to various biological responses. -Given the emphasis on IL-6 and sIL-6R in the context, 'sR_IL6' could refer to a soluble receptor or a related soluble component in the IL-6 signaling pathway. This type of molecule typically facilitates trans-signaling interactions. It may interact with IL-6 to form a complex that can then engage with another component, sgp130, to modulate signaling. This complex plays a role in regulating immune responses and could have therapeutic implications, especially in diseases like Crohn’s disease where IL-6 signaling is dysregulated. +1. **Biological Function**: Gp130 is involved in mediating the effects of cytokines, particularly IL-6. It is a part of the receptor complex that includes the IL-6 receptor and gp130. When IL-6 binds to its receptor, gp130 is recruited to form a signaling complex, which then initiates downstream signaling pathways such as JAK/STAT, MAPK, and PI3K/Akt. -In summary, if 'sR_IL6' is indeed related to IL-6 signaling, its biological importance might lie in modulating inflammatory responses through trans-signaling, interacting with IL-6 and possibly other soluble receptors or signaling molecules in this pathway. Its role would be crucial in maintaining homeostasis in immune function and could be a target for therapeutic interventions." -mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca,"gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",gp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, here is the summarized background information about the gp130 species: +2. **Role in Pathways**: Gp130 is central to the IL-6 signaling pathway, which is involved in immune responses, inflammation, and cell survival. It is indispensable for the transmission of signals that lead to the activation of transcription factors such as STAT3, which can then affect the expression of various genes involved in inflammatory responses. -1. **Biological Function**: gp130 is a protein that plays a critical role in signaling pathways, specifically as part of the interleukin-6 (IL-6) signaling pathway. It acts as a key signal transducer and is involved in the formation of a signaling complex with the IL-6 receptor. +3. **Interactions with Other Molecules**: Gp130 interacts specifically with the IL-6/IL-6R complex to transmit cytokine-mediated signals. Additionally, soluble forms of gp130 (sgp130) act as natural inhibitors of IL-6 signaling by binding to IL-6/soluble IL-6R complexes, thereby preventing them from interacting with membrane-bound gp130. -2. **Role in Pathways**: gp130 is an integral component of the signaling complex formed between IL-6 and its soluble receptor, sIL-6Rα. The complex formation is crucial for IL-6 trans-signaling, which is implicated in various inflammatory responses. +4. **Importance in the Biological System**: In the context of inflammatory diseases such as Crohn's disease, modulation of gp130 and its associated signaling pathways represents a potential therapeutic strategy. Soluble gp130 (sgp130Fc), a fusion protein combining the extracellular portion of gp130 with an Fc region, has been studied for its ability to inhibit IL-6 trans-signaling, highlighting its therapeutic potential in conditions characterized by excessive or dysregulated IL-6 activity. -3. **Interactions with Other Molecules**: gp130 interacts with IL-6 and sIL-6Rα to form a hexameric complex that is necessary for initiating the downstream signaling cascade. Soluble gp130 (sgp130) acts as a natural inhibitor by binding to this complex, thereby preventing trans-signaling. +Overall, gp130 is a critical component of the IL-6 signaling pathway, with its function as both a necessary signal transducer and a target for therapeutic inhibition in inflammatory diseases." +mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9,"R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",R_IL6_gp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context and information provided, the specifics about the species named 'R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' are not directly detailed. However, by piecing together related information and general knowledge, we can infer some aspects of its characteristics and role in biological systems: -4. **Importance in the Biological System**: In the context of the system being modeled, soluble gp130 (sgp130) is considered a potential therapeutic agent, especially in conditions like Crohn's disease, due to its ability to inhibit IL-6 trans-signaling. However, the effectiveness of sgp130 is dependent on achieving high and frequent doses, as small alterations in sgp130 levels have minimal impact due to its high baseline concentration relative to IL-6. +1. **Biological Function**: 'R_IL6_gp130' likely represents the interaction or complex involving the interleukin-6 (IL-6) signaling pathway and the gp130 co-receptor. IL-6 is a cytokine involved in immune responses, inflammation, and hematopoiesis. Gp130 is a signal transducer for cytokines in the IL-6 family and plays a crucial role in transmitting signals from cytokine receptors. -Overall, gp130 is pivotal for IL-6-mediated signaling, and modifications in its activity can potentially modulate inflammatory pathways, making it a significant target in certain therapeutic approaches." -mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9,"R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",R_IL6_gp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context provided, the species named 'R_IL6_gp130' appears to relate to the interleukin-6 (IL-6) signaling pathway, which involves the interaction of IL-6 with its receptor components for signal transduction. Although specific details about this species are not directly provided in the context, we can infer its characteristics and role based on the general knowledge of similar biological components involved in IL-6 signaling: +2. **Role in Pathways**: The IL-6/gp130 complex is essential in the IL-6 signaling pathway, which influences various biological processes including inflammation, immune response, and acute phase reactions. This pathway can operate through classical signaling using membrane-bound receptors or trans-signaling with soluble receptors and receptors like gp130. -1. **Biological Function**: R_IL6_gp130 likely represents a complex involving IL-6, its specific receptor, and the signal transducer gp130. In the IL-6 signaling pathway, gp130 serves as a critical signal transducer that, upon activation by the IL-6/IL-6 receptor complex, initiates intracellular signaling cascades that influence gene expression. +3. **Interactions with Other Molecules**: The IL-6 signaling pathway involves interactions between IL-6, soluble IL-6 receptor (sIL-6R), and gp130. It is noted that soluble gp130 (sgp130) can inhibit IL-6 trans-signaling, which suggests that 'R_IL6_gp130' might be relevant in modulating or forming complexes crucial for either inhibiting or promoting the IL-6 signal. -2. **Role in Pathways**: This species is part of the IL-6 signaling pathway, which can activate the JAK/STAT signaling cascade, resulting in the phosphorylation of STAT3 (Signal Transducer and Activator of Transcription 3). This pathway is crucial in mediating inflammatory responses and plays a role in various physiological and pathological processes, including immune regulation, inflammation, and cell growth. +4. **Importance in Biological System**: In the context of the system being modeled (likely involving conditions like Crohn's disease), targeting the IL-6/gp130 pathway may have therapeutic implications. Efforts such as using sgp130Fc fusion proteins to inhibit IL-6 trans-signaling highlight the importance of understanding and manipulating this complex in disease models for potential treatment strategies. -3. **Interactions with Other Molecules**: R_IL6_gp130 likely interacts with IL-6 and its soluble receptor (sIL-6R), as well as with gp130. This interaction forms a complex that facilitates signal transduction through the gp130 component, leading to downstream effects such as the activation of STAT3. It can also interact with inhibitors like soluble gp130 (sgp130) or fusion proteins designed to modulate this signaling pathway. +Therefore, 'R_IL6_gp130' in this context probably signifies a key component or step within the IL-6 signaling pathway, with potential roles in modulating inflammatory responses, significant to modeling diseases like Crohn's disease." +mw6cce2109_0e32_4dd9_98ec_41173e8ef07d,"Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",Ractive,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The provided context does not directly reference the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' or its ID: mw6cce2109_0e32_4dd9_98ec_41173e8ef07d. However, we can attempt to infer its possible characteristics and role based on the general information available in the context, which focuses on IL-6-mediated immune regulation in Crohn's Disease, using a multiscale model. -4. **Importance in the Biological System**: Within the context described, R_IL6_gp130 is important for understanding the dynamics of IL-6 signaling, especially in inflammatory conditions such as Crohn's disease. The IL-6 pathway is targeted for therapeutic intervention, suggesting its significance in disease pathology and treatment. +1. **Biological Function:** + The document is centered around the regulation of IL-6, interleukin-6, which is an important cytokine involved in inflammatory and immune responses. While Ractive itself is not mentioned, it could potentially be related to or a component interacting within the IL-6 signaling pathways. -In summary, R_IL6_gp130 likely represents a key component of the IL-6 signaling pathway, central to mediating the effects of IL-6 through gp130 in inflammation and immune response, as inferred from the general function of similar complexes." -mw6cce2109_0e32_4dd9_98ec_41173e8ef07d,"Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",Ractive,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there appears to be no specific information about the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' within the text. However, the context discusses the IL-6 signaling pathway and its components, particularly focusing on the interactions between IL-6, sIL-6Rα, and therapeutic antibodies, such as the humanized anti-interleukin 6 receptor antibody (tocilizumab). This suggests a theme centered around immune response regulation, specifically in diseases like rheumatoid arthritis and possibly Crohn's disease. +2. **Role in Pathways:** + Since the context enlightens the importance of the IL-6/sIL-6Rα complex in IL-6 signaling, Ractive might play a role in a related or auxiliary pathway, possibly as a regulatory or signaling molecule. -In the absence of specific information about 'Ractive', we can infer its potential role based on the discussed biological components. It is likely that 'Ractive' could be involved in the pathways related to cytokine signaling, immune modulation, or therapeutic interactions similar to those of IL-6 or its receptor complex. Its importance in the system may be linked to modulating immune responses or serving as a target or mediator in therapeutic approaches within the context of the mentioned diseases. +3. **Interactions with Other Molecules:** + The IL-6 signaling pathway involves interactions between IL-6, IL-6 receptors, sIL-6Rα (soluble IL-6 receptor), and antibodies like tocilizumab (anti-IL-6Rα). It's plausible that Ractive could interact with similar molecules or influence the pathway indirectly. -In systems biology modeling, species or molecules like 'Ractive' could be critical for either transmitting signals within a pathway, modifying the activity of other molecules, or acting as a checkpoint or target for drugs designed to alter biological responses in conditions like Crohn's disease or rheumatoid arthritis." -mw2b255f94_8018_4b99_bde8_918eeac45446,"STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",STAT3,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, the species 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is likely referring to the well-known protein STAT3, a signal transducer and activator of transcription 3. Here is the relevant background information about STAT3: +4. **Importance in the Biological System:** + Given the context's focus on immune regulation and Crohn's Disease, Ractive could be assumed as an important component in the signaling or regulatory mechanisms within this biological model, potentially influencing cytokine behavior, immune response modulation, or drug interactions. -1. **Biological Function**: - - STAT3 is involved in the phosphorylation process as part of cell signaling. Phosphorylated STAT3 (pSTAT3) is indicative of its active state, which can translocate to the nucleus to act as a transcription factor. - - It plays a crucial role in relaying signals from cytokine receptors, like the IL-6 receptor complex, to the nucleus, influencing gene expression. +In summary, while there's no specific information on Ractive, its inferred role might be associated with IL-6 signaling, immune pathway interactions, or drug (such as antibody) responses within the described model of immune regulation." +mw2b255f94_8018_4b99_bde8_918eeac45446,"STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",STAT3,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the available context from the provided documents, STAT3 appears to refer to ""signal transducer and activator of transcription 3"". This molecule is a critical component in the JAK/STAT signaling pathway, which is involved in transducing extracellular signals into cellular responses. The context mentions that phosphorylation of STAT3 is important, suggesting that it becomes activated through the addition of a phosphate group. Activated or phosphorylated STAT3 (pSTAT3) can then translocate to the nucleus where it functions as a transcription factor regulating the expression of various genes. -2. **Role in Pathways**: - - STAT3 is a central component of the JAK-STAT signaling pathway. Once activated, it typically mediates the effects of cytokines, such as IL-6, contributing to various cellular responses, including growth, differentiation, and survival. - - The context mentions its involvement in pathways activated by IL-6, a cytokine that triggers immune responses, inflammation, and acute-phase reactions. +**Biological Function:** +STAT3 plays a key role in mediating the effects of various cytokines and growth factors by regulating gene expression. It is involved in controlling multiple cellular processes such as cell growth, apoptosis, and differentiation. -3. **Interactions with Other Molecules**: - - STAT3 gets activated by cytokines binding to their respective receptors, leading to JAK kinases' activation, which subsequently phosphorylates STAT3. - - It interacts with components of the IL-6 receptor family, specifically affecting the pathways involving IL-6 trans-signaling. - - The context also suggests interactions involving sIL-6R (a soluble IL-6 receptor) and sgp130 (a soluble form of the co-receptor gp130), where pSTAT3 acts in various compartments like the GI tract and liver depending on cytokine signaling. +**Role in Pathways:** +STAT3 is a central player in the JAK/STAT signaling pathway. It is specifically mentioned in the context of IL-6 signaling, where it is activated downstream of interleukin-6 receptor engagement, which can involve both classical and trans-signaling mechanisms. -4. **Importance in the Biological System**: - - STAT3 is important in modeling biological systems that involve immune responses or inflammation, such as in the context of Crohn's disease, as indicated by increased pSTAT3 levels in serum and tissues affected by the disease. - - Its role as a transcription factor makes it key in regulating downstream gene expression that could contribute to disease pathology and the body's response to inflammation. +**Interactions with Other Molecules:** +STAT3 interacts with IL-6 and its receptors (such as sIL-6R and gp130), and phosphorylation of STAT3 can be triggered by cytokines binding to these receptors. The document implies interactions with components like C-reactive protein (CRP) and possibly engagements involving soluble forms of receptors like sgp130, which can modulate signaling. -In summary, although there is no direct mention of a species specifically labeled 'STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' in the document, the general characteristics and functions of STAT3 can be inferred based on common scientific knowledge and the provided context about IL-6 signaling and related pathways." -mw48867e93_f170_44e8_ac7a_185b23e1bf3b,"pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",pSTAT3,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context provided, specific information about the biological species 'pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' is not explicitly detailed. However, we can infer its role and significance based on the general knowledge about pSTAT3 and its involvement in biological processes. +**Importance in the Biological System Being Modeled:** +STAT3's significance in the biological model investigated (likely related to inflammatory diseases like Crohn’s disease) lies in its role in mediating cytokine signaling that could lead to inflammation and other immune responses. The upregulation of phosphorylated STAT3 in specific tissue biopsies, such as those from the colon in Crohn’s disease, suggests its involvement in inflammatory pathogenic mechanisms. -1. **Biological Function:** - - pSTAT3, or phosphorylated STAT3, is a form of Signal Transducer and Activator of Transcription 3 (STAT3) that becomes activated through phosphorylation. This activation enables pSTAT3 to translocate to the cell nucleus, where it functions as a transcription factor, promoting the expression of various genes involved in cell growth, survival, and differentiation. +Overall, STAT3 is a crucial component in understanding how intracellular pathways translate external signals into gene expression changes that affect biological outcomes and diseases." +mw48867e93_f170_44e8_ac7a_185b23e1bf3b,"pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",pSTAT3,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The provided context does not contain detailed or specific information about the species pSTAT3 identified by the ID mw48867e93_f170_44e8_ac7a_185b23e1bf3b, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. Therefore, I will provide a summary based on general knowledge about pSTAT3 and its role in biological systems. -2. **Role in Pathways:** - - In the context described, pSTAT3 is associated with IL-6 signaling, which involves classical and trans-signaling pathways. IL-6 is a cytokine involved in immune response, and its interaction with receptors such as IL-6R and gp130 leads to the activation of JAK kinases and subsequent phosphorylation of STAT3 (pSTAT3). This signaling cascade is crucial in mediating responses to inflammation and stress. +**Background Information on pSTAT3:** -3. **Interactions with Other Molecules:** - - pSTAT3 interacts with the IL-6 receptor complex, including sIL-6R (soluble IL-6 receptor) and sgp130 (soluble gp130). The complex formation and subsequent signaling facilitate various downstream effects. pSTAT3 is known to regulate the expression of suppressor of cytokine signaling (SOCS) proteins and other gene products involved in modulating immune responses. +- **Biological Function:** + pSTAT3 refers to the phosphorylated form of the STAT3 protein, which stands for Signal Transducer and Activator of Transcription 3. STAT3 is a transcription factor that, when phosphorylated, becomes activated and dimerizes. This activated dimer can then translocate to the nucleus to modulate the expression of specific target genes. -4. **Importance in the Biological System Being Modeled:** - - pSTAT3 plays a critical role in inflammatory responses, as highlighted by its reported increase in serum concentrations in conditions like Crohn’s disease. It is involved in the transcriptional regulation of acute-phase proteins such as C-reactive protein (CRP) and other gene products that are significant in the immune response and inflammation within the gastrointestinal tract and liver. +- **Role in Pathways:** + STAT3 is primarily involved in the JAK-STAT signaling pathway. Upon activation, typically through cytokine signaling such as IL-6, STAT3 is phosphorylated by Janus kinases (JAKs). pSTAT3 plays a crucial role in mediating responses to extracellular signaling and is involved in various biological processes such as cell growth, differentiation, and survival. -This inferred information helps underscore the importance of pSTAT3 in immune modulation and its potential implications in inflammatory diseases, even though specific details about its ID-specific characteristics in the context were not provided." -mw0083d743_836f_4238_a17f_4602193d5bc0,geneProduct,geneProduct,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The provided context from the document does not include specific details about the biological species or molecule identified as 'geneProduct' with the ID: mw0083d743_836f_4238_a17f_4602193d5bc0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. There is no explicit mention of this molecule's biological function, role in pathways, interactions with other molecules, or its importance in the biological system being modeled. +- **Interactions with Other Molecules:** + pSTAT3 interacts with JAKs as part of its activation. It is also involved in crosstalk with other signaling molecules and pathways, including IL-6, sIL-6R (soluble IL-6 receptor), and gp130. These interactions facilitate a range of cellular responses, including modulation of immune response, inflammation, and cellular proliferation. -Based on the context, which predominantly discusses interleukin-6 (IL-6) pathways, receptors, and related molecules (e.g., sIL-6R, gp130, and sgp130), we can infer that 'geneProduct' might be related to the IL-6 signaling pathway or another signaling molecule involved in inflammatory or immune responses. In systems biologically concerned with inflammation or cytokine signaling, such gene products might typically be involved in cell signaling cascades, playing roles in activating transcription factors, interacting with receptors or co-receptors, and affecting the expression of downstream genes important for cellular responses. +- **Importance in the Biological System:** + pSTAT3 is an important mediator in immune responses and inflammation. It has been implicated in various diseases, including inflammatory bowel diseases like Crohn's disease, where increased levels of pSTAT3 have been observed in affected tissues. It also plays a role in cancer progression, where aberrant STAT3 activity contributes to tumorigenesis. -Since specific data is not available, hypothetical pathways could involve roles similar to those of IL-6 or its receptors—modulating inflammatory responses, and participating in acute phase reactions, including CRP production in the liver. Gene products in such pathways often interact with other cytokines, receptors, and intracellular signaling proteins to exert their effects, potentially influencing processes like cell proliferation, differentiation, and survival." -mwd31f52cc_04e7_40e0_885f_c7b2d9e62215,"sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context provided, there is no explicit mention of the species 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' directly in the excerpts. However, we can infer some related information using general knowledge and by examining the related components and interactions in the context shared. +In the context of the document, mention of pSTAT3 suggests its potential involvement in IL-6 signaling pathways, possibly related to immune and inflammatory responses as well as transcriptional regulation of genes relevant to the conditions being discussed (e.g., Crohn’s disease or similar inflammatory conditions)." +mw0083d743_836f_4238_a17f_4602193d5bc0,geneProduct,geneProduct,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The provided context does not specifically describe the species named 'geneProduct' with the ID 'mw0083d743_836f_4238_a17f_4602193d5bc0' located in 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5'. However, based on the general context and common knowledge within systems biology, we can infer some plausible information about 'geneProduct' in relation to similar biological components: -The context revolves around the interaction and dynamics involving the Interleukin-6 (IL-6) signaling pathway, soluble IL-6 receptor (sIL-6R), and the involvement of other molecules like sgp130. +1. **Biological Function**: Given that 'geneProduct' is mentioned in the context of IL-6 signaling and STAT3 activation, it could be a gene product related to cytokine signaling pathways. Gene products involved in this pathway typically play roles in immune responses, inflammation, cell survival, and proliferation. -### Inferred Background Information about 'sR': +2. **Role in Pathways**: The context includes references to IL-6, sIL-6R, and associated signaling pathways, such as those involving STAT3 and SOCS. 'geneProduct' may be involved in modulating these pathways, possibly influencing downstream effects such as gene transcription. -1. **Biological Function:** - - In the context of cytokine signaling, receptors like sR are generally involved in recognizing and binding to specific signaling molecules (e.g., cytokines such as IL-6) to facilitate their biological functions. Therefore, 'sR' could act as a receptor or part of a receptor complex in signaling pathways. +3. **Interactions with Other Molecules**: 'geneProduct' might interact with key proteins and receptors in the IL-6 signaling pathway, such as IL-6, sIL-6R, gp130, and sgp130. These interactions could be crucial for the regulation and fine-tuning of the signaling pathway. -2. **Role in Pathways:** - - Given the presence of IL-6 and its receptor dynamics (e.g., IL-6/sIL-6R complex) in the context, 'sR' might participate in cytokine signaling pathways, potentially serving as a modulator that enhances or inhibits signal transduction depending on its specific interactions with IL-6 or other pathway components like sgp130. +4. **Importance in the Biological System**: If 'geneProduct' participates in IL-6 signaling, it could be important for processes like acute phase responses, immune regulation, and potentially in the context of diseases where IL-6 plays a role, such as autoimmune disorders or chronic inflammatory conditions. -3. **Interactions with Other Molecules:** - - The sIL-6R forms complexes with IL-6, which then interact with membrane-bound receptors to initiate signaling cascades like the activation of STAT3. 'sR' might potentially interact similarly, indicating a critical role in modifying the intensity or outcome of the signaling process. +Without specific information, these inferences are speculative but based on common roles and interactions seen within such pathways." +mwd31f52cc_04e7_40e0_885f_c7b2d9e62215,"sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is specific mention of an interaction between sR and IL-6. Although the document does not explicitly describe the species labeled as 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)', we can infer its potential role and importance by drawing parallels to similar entities mentioned in the system's model involving IL-6 signaling. -4. **Importance in the Biological System Being Modeled:** - - The balance of soluble receptors and cytokines (such as IL-6/sIL-6R) and their interactions with other molecules (e.g., sgp130) are essential for controlling inflammatory responses and other downstream effects (e.g., CRP production in the liver). - - Given this, 'sR' could play a pivotal regulatory role, affecting the system's sensitivity to changes in cytokine levels and potentially serving as a target for therapeutic interventions. +### Inferred Information about sR: -### Conclusion: +- **Biological Function**: + - The 'sR' is likely a soluble receptor or receptor component involved in the IL-6 signaling pathway, given its contextual relationship with IL-6 and similar naming conventions to 'sIL-6R' and its complex with IL-6 ('IL-6:sR'). -While the provided document excerpts do not explicitly detail 'sR's identity or function, its inferred associations with key players like IL-6, sIL-6R, and sgp130 suggest a role in cytokine signaling modulation, particularly in pathways relevant to inflammation and immune response. For specific molecular functions and pathway roles, further examination of full-length documents or additional sources would be required." -mw2c9b0499_3325_4394_8af3_bbf653a944a0,"IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context and general knowledge, the species named 'IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' is likely referring to Interleukin-6 (IL-6), a cytokine involved in various biological functions and pathways. Here is a summary of its roles and significance: +- **Role in Pathways**: + - It seems to participate in modulating IL-6 activity. The mention of 'IL-6:sR' implies that the sR might form complexes with IL-6, influencing the signaling dynamics, possibly acting as a decoy receptor or as a mediator that facilitates or modifies downstream signaling. + +- **Interactions with Other Molecules**: + - The document discusses complexes such as 'IL-6:sR' and 'IL-6:sR:sgp130'. This suggests that sR interacts directly with IL-6 and possibly with other soluble components like sgp130, which is known to modulate IL-6 trans-signaling. -1. **Biological Function:** - - IL-6 is a multifunctional cytokine that plays a critical role in immune response regulation, inflammation, and hematopoiesis. - - It is known to be a mediator of fever and of the acute phase response. +- **Importance in the Biological System**: + - While sR's specific function was not detailed, its involvement in forming complexes such as 'IL-6:sR' suggests a regulatory role in the IL-6 pathway, which is crucial for inflammatory and immune responses. + - The interaction between sR and IL-6 may have implications for therapeutic targets, particularly in conditions where IL-6 signaling is dysregulated. -2. **Role in Pathways:** - - IL-6 signaling occurs via two main pathways: the classical signaling pathway and the trans-signaling pathway. - - The classical pathway involves IL-6 binding to a membrane-bound IL-6 receptor (IL-6Rα), while the trans-signaling pathway involves a soluble form of IL-6Rα (sIL-6Rα). - - Both pathways converge on a signal transduction cascade that activates Janus kinase (Jak) proteins and leads to the phosphorylation of signal transducer and activator of transcription 3 (STAT3). +In summary, 'sR' likely plays a critical part in the IL-6 signaling pathway, influencing the biological effects of IL-6 through complex formation and interaction with other soluble proteins like sgp130. Understanding its role would be important for modeling systemic inflammatory responses and potentially informs therapeutic strategies targeting IL-6 pathways." +mw2c9b0499_3325_4394_8af3_bbf653a944a0,"IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, IL-6 (likely referring to the cytokine Interleukin-6) is a significant player in the immune regulation associated with Crohn’s disease. Here is a summary of the relevant information extracted about IL-6: -3. **Interactions with Other Molecules:** - - IL-6 interacts with its receptor IL-6Rα (either membrane-bound or soluble) and forms a complex that recruits the gp130 coreceptor. - - This interaction is crucial for activating downstream signaling pathways that are involved in immune responses. +1. **Biological Function**: IL-6 is a cytokine that plays a critical role in immune responses. It is involved in the survival of T-cells and contributes to their apoptosis resistance, especially in the lamina propria, a tissue layer in the intestines. This function is particularly relevant in the context of inflammatory diseases such as Crohn's disease. -4. **Importance in the Biological System:** - - IL-6 is particularly important in inflammatory diseases such as Crohn's disease, where it contributes to enhanced T-cell survival and resistance to apoptosis in the intestinal mucosa, as well as elevated chemokine secretion. - - It plays a significant role in the pathophysiology of autoimmune diseases and chronic inflammatory conditions, making it a target for therapeutic interventions such as with specific antibodies like tocilizumab. +2. **Role in Pathways**: IL-6 signaling can occur through two main pathways: + - The **classical pathway**, mediated by a membrane-bound IL-6 receptor (IL-6Rα). + - The **trans-signaling pathway**, mediated by a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor to form an active complex that leads to downstream signaling events, including the phosphorylation of Janus kinase (Jak) family proteins and the activation of signal transducer and activator of transcription 3 (STAT3). -In summary, IL-6 is a central cytokine in immune regulation and inflammatory processes, which makes it a pivotal part of the biological system being modeled, particularly in the context of diseases like Crohn's disease." -mwd65b5b39_dc1b_4e77_a999_67277a880e5e,"sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sgp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, here is the background information about the species 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)': +3. **Interactions with Other Molecules**: IL-6 interacts with its receptor IL-6Rα (both in its membrane-bound and soluble forms) to initiate signaling. In the classical signaling pathway, the IL-6/IL-6Rα complex recruits gp130 to form a functional receptor complex. This interaction initiates a cascade, leading to the activation of downstream signaling molecules, including Jak and STAT3. -### Biological Function: -sgp130, known here as a species variant, reflects a biological molecule related to the inhibition of IL-6 trans-signaling. It specifically refers to a fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1. This fusion protein is designed to inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex. +4. **Importance in the Biological System**: IL-6 is crucial in the modulation of immune responses, which are essential in the context of inflammatory diseases like Crohn’s disease. It enhances the survival of T-cells, contributing to the chronic inflammation characteristic of this condition. The trans-signaling pathway, involving the soluble IL-6Rα, is particularly noted for its importance in disease, highlighting IL-6's role in promoting inflammatory pathways. -### Role in Pathways: -sgp130 plays a role in pathways involving the interleukin-6 (IL-6) signaling cascade. It specifically targets the IL-6/sIL-6Rα complex, blocking the trans-signaling pathway that can contribute to inflammatory responses, such as those observed in Crohn’s disease. +Overall, IL-6 is depicted as a pivotal cytokine in driving the immune responses that characterize inflammatory diseases, and its pathways and interactions are potential targets for therapeutic intervention." +mwd65b5b39_dc1b_4e77_a999_67277a880e5e,"sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sgp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The species or molecule 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' seems to be referring to a soluble form of gp130, which is a component of the IL-6 signaling pathway. Here is a summary of the relevant background information based on the provided excerpts: -### Interactions with Other Molecules: -sgp130 interacts with the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc binds this complex with the same affinity as natural sgp130, thus inhibiting the signaling pathways mediated by IL-6. +1. **Biological Function**: + - sgp130 functions as an inhibitor of IL-6 trans-signaling, which is a process involving the IL-6 signaling pathway. This occurs when sgp130 binds to the IL-6/sIL-6Rα complex, effectively blocking its ability to signal. -### Importance in the Biological System: -sgp130 appears to be of limited effect in altering the steady-state values of certain biomarkers unless present in large quantities. It exists in excess compared to free IL-6, leading to minimal effect from small perturbations in its levels. Hence, any significant observable effects require substantial changes in sgp130 concentrations. +2. **Role in Pathways**: + - sgp130 is involved in the IL-6 signaling pathway, particularly in the inhibition of IL-6 trans-signaling. This pathway is significant in inflammation and immune response, and it involves interactions with the soluble IL-6 receptor (sIL-6Rα). -Despite its biological function, the context suggests that sgp130-based therapeutic strategies may not be as robust as anticipated. The sensitivity analysis indicated that the output biomarkers are less affected by sgp130 levels, making IL-6 and sIL-6Rα more potent targets for intervention in the studied system. This contributes to understanding its therapeutic potential limitations, particularly in addressing diseases like Crohn's where IL-6 signaling is implicated." -mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3,"sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR_IL6_sgp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The species sR_IL6_sgp130, identified as mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 within the context provided, appears to involve components related to interleukin-6 (IL-6) signaling pathways. Here is the summary of the background based on the given context and general knowledge: +3. **Interactions with Other Molecules**: + - sgp130 interacts with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 prevents IL-6 from engaging with membrane-bound gp130, thus inhibiting downstream signaling events. -### Biological Function -- **Fusion Protein**: The document mentions a fusion protein involving sgp130, which combines the extracellular portion of the gp130 protein with the Fc region of human IgG1. This fusion protein, known as sgp130Fc, is designed to inhibit IL-6 trans-signaling in cells. +4. **Importance in the Biological System Being Modeled**: + - In the modeling context provided, altering the levels of sgp130 has minimal effect on the system due to its high baseline levels compared to the much lower concentrations of free IL-6. This suggests that while sgp130 is present in excess, significant changes in its levels are required to observe an impact on system outputs. + - The effectiveness of sgp130-based therapies appears limited under normal conditions and requires high doses for observable effects, particularly in the suppression of CRP (C-reactive protein) levels and pSTAT3 in the gut. + - The sensitivity analysis of the system model indicates that sgp130 is among the least influential parameters for output biomarkers, suggesting that targeting IL-6 and its receptor may be more effective for therapeutic interventions. -### Role in Pathways -- **IL-6 Trans-Signaling**: The primary role of sgp130Fc is to inhibit IL-6 trans-signaling. In the IL-6 signaling pathway, IL-6 can signal through its receptor complex involving IL-6R and gp130, leading to downstream effects such as the activation of STAT3 transcription factors. The fusion protein acts to prevent this signaling pathway by binding to the IL-6/sIL-6Rα complex. -- **Simulations in Crohn’s Disease**: The sgp130Fc protein is being studied for its therapeutic potential in inflammatory conditions like Crohn’s disease, where IL-6 signaling plays a significant role. +Overall, sgp130 plays a regulatory role in the IL-6 signaling pathway by acting as a natural inhibitor, but in the context of the model discussed, its predominant presence makes it less impactful for modifying system dynamics without high interventions." +mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3,"sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR_IL6_sgp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context provided, there is no specific mention of the species ""sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)"" with the ID ""mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3."" However, we can infer its role and importance based on the information regarding similar biological components described in the context. -### Interactions with Other Molecules -- **Binding with IL-6/sIL-6Rα Complex**: The sgp130Fc is assumed to bind with the IL-6/sIL-6Rα complex with affinities similar to natural sgp130. The presence of sgp130Fc in large quantities suggests it primarily functions by excess binding to this complex, thereby preventing excessive IL-6 signaling. +### Inferred Background Information on sR_IL6_sgp130: -### Importance in the Biological System -- **Therapeutic Potential**: The document outlines the use of sgp130Fc as a potential therapeutic intervention in diseases with aberrant IL-6 signaling, such as Crohn’s disease. It has been shown to only be effective at very high doses due to its interaction landscape. -- **Limited Systemic Impact**: Due to high baseline levels of sgp130 compared to IL-6, small changes in sgp130 do not significantly affect the system, implying its role predominantly emerges under conditions requiring high-dose applications or alterations. +1. **Biological Function:** + - The molecule seems to relate to the signaling pathway of IL-6 (Interleukin-6), a cytokine important in immune response. + - sR_IL6_sgp130 likely involves binding interactions similar to natural sgp130, which acts to inhibit IL-6 signaling by interfering with the IL-6/sIL-6R complex. -Overall, while the document primarily discusses the use of a related molecule (sgp130Fc), it emphasizes the relevance of sgp130 interactions within IL-6-related pathways, underscoring its importance in modulating immune and inflammatory responses within certain pathological contexts." -mwf7796221_1fea_4274_a93e_c00adbf5778c,"Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no specific detailed information available about the species or molecule 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' with the ID mwf7796221_1fea_4274_a93e_c00adbf5778c. However, from the context and general knowledge, we can infer the following: +2. **Role in Pathways:** + - It may be involved in pathways such as IL-6 trans-signaling, which is mediated by the soluble IL-6 receptor (sIL-6R) and amplifies responses, particularly in diseases like Crohn's. + - It could potentially modulate signaling cascades involving STAT3 (Signal Transducer and Activator of Transcription 3), as IL-6 activates STAT3 through its receptor complexes. -1. **Biological Function**: The document references serum antibody (Ab) concentrations in nmol/l, which suggests that 'Ab' likely stands for an antibody. Antibodies are proteins produced by the immune system to identify and neutralize pathogens such as bacteria and viruses. +3. **Interactions with Other Molecules:** + - Likely interacts with components such as IL-6, sIL-6Rα, and sgp130 to modulate signaling. + - Its interaction may focus on forming a complex that either facilitates or inhibits further downstream signaling, affecting the activity of proteins like pSTAT3 (phosphorylated STAT3). -2. **Role in Pathways**: The context mentions anti-IL-6/sIL-6Rα interactions. Antibodies targeting the interleukin-6 (IL-6) pathway are typically used in treatments to modulate immune responses, particularly in inflammatory conditions. They can bind to IL-6 or its receptor to inhibit the downstream signaling pathway. +4. **Importance in the Biological System:** + - Given the high baseline level of sgp130 relative to free IL-6, sR_IL6_sgp130 may play a role in maintaining a steady state of signaling through sequestration of signaling complexes. + - Its importance could be in contexts requiring modulation of IL-6 activity, either as a natural response or therapeutic intervention, particularly in inflammatory conditions. -3. **Interactions with Other Molecules**: The document discusses the anti-IL-6 Ab's effect in relation to IL-6 and sIL-6Rα. This suggests that the antibody in question interacts specifically with these cytokines or cytokine receptors, playing a role in reducing inflammation by interfering with the IL-6 signaling pathway. +This inference is based on the role of similar molecules and the described importance of IL-6 signaling modulation in immunological and inflammatory contexts." +mwf7796221_1fea_4274_a93e_c00adbf5778c,"Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no direct or specific information about the species 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, we can infer what this species might be based on general knowledge about similar biological components mentioned in the context. -4. **Importance in the Biological System**: The antibody’s importance seems to be related to its therapeutic role in modulating the immune response, particularly in diseases involving heavy inflammation. This can include conditions like inflammatory bowel diseases or other autoimmune disorders, where targeting IL-6 or its receptor can have significant therapeutic effects. +From page 5 of the document, we see references to ""anti-IL-6 Ab"" and interactions with ""IL-6Rα/sIL-6Rα"" complexes, which suggest that 'Ab' could potentially be an antibody, possibly involved in targeting IL-6 or its receptor sIL-6Rα in the biological system being studied. -In summary, based on the context and typical characteristics of antibodies in similar biological systems, 'Ab' is likely an antibody involved in targeting the IL-6 signaling pathway, important for managing inflammatory responses in various conditions." -mw5d764bb8_5693_4ac8_9557_f65992cc5eb0,"Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab_sR,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no specific mention or details about the species named 'Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, I can infer potential roles and functions based on adjacent biological components and typical interactions within such systems, especially considering the discussion around IL-6 pathways and related molecules in the context. +**Inferred Biological Function of Ab:** +- 'Ab' is likely an antibody that interacts with IL-6 or IL-6Rα. Antibodies are proteins produced by the immune system that can bind to specific antigens, such as proteins on pathogens or other molecules like interleukins. -1. **Biological Function**: In this particular study context, sIL-6R (soluble Interleukin-6 receptor) and IL-6 (a cytokine involved in inflammation and immune responses) are key components. Ab_sR might refer to an antibody-related soluble receptor component or variant. If related to IL-6/sIL-6R pathways, its function could involve modulation of immune responses or inflammation via binding interactions. +**Role in Pathways:** +- The context mentions dose-response changes impacting serum CRP (C-reactive protein), indicating that 'Ab' might play a role in inflammatory pathways, particularly associated with modulating the immune response. -2. **Role in Pathways**: The surrounding context heavily discusses the interaction of IL-6 with its receptor and the subsequent signaling pathways, such as the Jak-STAT pathway (notably leading to STAT3 activation), indicating a role in cytokine-receptor interactions. Ab_sR could interact within these pathways, perhaps as an intermediary or a modulator influencing signal transduction. +**Interactions with Other Molecules:** +- If 'Ab' is an anti-IL-6 antibody, its primary interaction would be with interleukin-6 (IL-6) and its receptor complex, IL-6/sIL-6Rα. This interaction can impede the IL-6 signaling pathway, which is involved in inflammation and immune regulation. -3. **Interactions with Other Molecules**: If analogous to sIL-6R or anti-IL-6 therapeutic antibodies, Ab_sR might interact with IL-6, potentially modulating its effects by altered binding dynamics or competitive inhibition. Such interactions could influence downstream signaling events leading to transcriptional changes (e.g., expression of SOCS or CRP). +**Importance in the Biological System:** +- The efficacy of 'Ab' in modulating serum CRP levels implies it holds significance in controlling inflammatory responses, potentially offering therapeutic benefits in conditions characterized by excessive inflammation, such as inflammatory bowel diseases or other chronic inflammatory conditions. -4. **Importance in Biological System Being Modeled**: In systems modeling inflammatory responses, any component similar to an antibody interacting with cytokines like IL-6 is critical. It could predictively simulate treatment outcomes for inflammatory diseases or evaluate drug efficacy (e.g., CRP suppression in inflammatory cases). Ab_sR may hold similar significance if it's part of experimental or theoretical models assessing cytokine network modulation. +This inferred role highlights the importance of 'Ab' in potentially therapeutic contexts where modulation of specific cytokine pathways is desired." +mw5d764bb8_5693_4ac8_9557_f65992cc5eb0,"Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab_sR,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The context provided does not include any specific mention of the species named 'Ab_sR' (ID: mw5d764bb8_5693_4ac8_9557_f65992cc5eb0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5). Therefore, I will infer what this species might be based on general knowledge and the context provided. -While these are educated guesses based on typical roles and interactions of analogous proteins within such biological systems, exact functions and roles of Ab_sR would be best determined by specifics from the cited source text." -mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2,"Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab_sR_IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The species 'Ab_sR_IL6' (ID: mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2) does not have specific background information provided explicitly in the context you shared. However, I can infer potential characteristics based on general knowledge about similar components. +The context provided mentions interactions around IL-6, sIL-6R (soluble interleukin-6 receptor), and the IL-6/sIL-6R complex, which are significant components in the IL-6 signaling pathway. The mention of molecules such as CRP (C-reactive protein) suggests it is related to inflammatory responses. -### Inferred Background Information: +Given general biological knowledge, 'Ab_sR' could be hypothesized to represent an antibody or another protein involved in regulating or interacting with soluble receptors like sIL-6R. These soluble receptors often participate in signaling pathways where they modulate the activity of cytokines like IL-6. -1. **Biological Function:** - - 'Ab_sR_IL6' likely refers to an antibody ('Ab') targeting the soluble form of the interleukin-6 receptor (sIL-6R). This suggests it is involved in neutralizing or modulating the biological effects of sIL-6R, potentially inhibiting its interaction with interleukin-6 (IL-6). +- **Biological Function**: 'Ab_sR' might function as a regulator in the IL-6 signaling pathway. +- **Role in Pathways**: It could play a role in modulating the inflammatory response or could be involved in the same pathway as IL-6/sIL-6R by affecting their interaction or function. +- **Interactions with Other Molecules**: It could potentially interact with IL-6, sIL-6R, or related complexes to modulate signaling and downstream effects such as CRP production. +- **Importance in the Biological System**: If it is analogous to components like antibodies or receptor regulators, its importance could lie in its potential to modulate immune responses and inflammation. -2. **Role in Pathways:** - - The context described the targeting of the IL-6/sIL-6R complex as a treatment strategy for conditions involving excessive IL-6 signaling, such as Crohn's disease. 'Ab_sR_IL6' might play a role in suppressing IL-6-mediated pathways, thereby reducing inflammation or immune responses associated with diseases like Crohn's disease or rheumatoid arthritis. +Conclusively, without explicit details from the text, we extrapolate that 'Ab_sR' might be involved in related pathways and interactions as a regulatory molecule based on the IL-6/sIL-6R context and general knowledge of similar biological systems." +mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2,"Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab_sR_IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no specific mention of the biological species or molecule named 'Ab_sR_IL6' (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3). However, we can infer some relevant details from the general context regarding IL-6 and related pathways. -3. **Interactions with Other Molecules:** - - Interacts with sIL-6R, preventing the formation of the IL-6/sIL-6R complex. This interaction would diminish the activity of the classical and trans-signaling pathways mediated by IL-6, leading to reduced activation of downstream signaling molecules like STAT3 and associated gene transcription. +1. **Biological Function**: + - IL-6 is a cytokine involved in various immune responses, inflammation, and hematopoiesis. In the provided context, it's part of the signaling pathways that modulate immune responses. -4. **Importance in the Biological System Being Modeled:** - - Its importance lies in modulating inflammation by impacting IL-6 signaling. As IL-6 is crucial in immune response modulation, controlling its activity can lead to therapeutic benefits in diseases characterized by inflammation and immune dysregulation. +2. **Role in Pathways**: + - IL-6 interacts with its receptor, IL-6R, and the soluble form sIL-6Rα, to initiate signaling cascades involving pathways such as the JAK/STAT pathway (notably STAT3 phosphorylation). This can lead to the transcription of various genes, impacting inflammation and other immune responses. + - The mentioned pathways are part of a model studying IL-6 mediated immune regulation in diseases like Crohn’s disease, emphasizing IL-6's role in immune modulation. + +3. **Interactions with Other Molecules**: + - IL-6 typically binds to its receptor IL-6R or its soluble form sIL-6Rα. This complex can further interact with a signaling receptor gp130 to trigger downstream signaling events. + - In therapeutic contexts, antibodies targeting IL-6 or IL-6Rα, such as tocilizumab, interrupt these interactions to modulate immune responses, particularly in inflammatory diseases. -Broadly, 'Ab_sR_IL6' serves as a critical component in therapeutic models aiming to attenuate aberrant IL-6 signaling pathways in immune-mediated diseases." -mwbc2f5464_81e5_43fd_8b39_f5a2756af72f,"Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)",Ab,mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87,"The provided context does not contain direct information specifically about the species 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, from the available information, we can infer some details based on the general context and related biological components mentioned: +4. **Importance in the Biological System Being Modeled**: + - The provided context describes a model exploring IL-6/sIL-6Rα interactions, and their targeting implications for modulating immune responses in inflammatory conditions. + - The simulations suggest that targeting both IL-6 and the IL-6/sIL-6Rα complex can potentially enhance therapeutic outcomes, highlighting the importance of these interactions in therapeutic strategies. -1. **Biological Function**: The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins produced by the immune system to identify and neutralize foreign objects like bacteria and viruses. They play a crucial role in targeting specific antigens for the immune response. +Therefore, if 'Ab_sR_IL6' is related to IL-6/IL-6R interactions, it might be an antibody or related agent involved in modulating these interactions, potentially playing a role in therapeutic interventions for diseases involving IL-6 dysregulation." +mwbc2f5464_81e5_43fd_8b39_f5a2756af72f,"Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)",Ab,mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87,"The provided context does not explicitly mention specific background information or direct details about the species or molecule named 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, based on the surrounding context and general biological knowledge, some inferences can be made: -2. **Role in Pathways**: The context discusses the interaction between anti-IL-6 antibodies and IL-6/sIL-6Rα complex. IL-6 is a cytokine involved in inflammation and infection responses. Hence, antibodies targeting IL-6 pathways are often part of therapeutic interventions for inflammatory diseases. +### Inferred Background Information: +1. **Biological Function:** + - The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins that play crucial roles in the immune system by identifying and neutralizing foreign objects such as bacteria and viruses. -3. **Interactions with Other Molecules**: The document mentions the targeting of IL-6 and IL-6/sIL-6Rα complexes, suggesting that this antibody interacts with these molecules, likely inhibiting their function to reduce inflammation as indicated by the suppression of CRP (C-reactive protein), a marker of inflammation. +2. **Role in Pathways:** + - Given the context mentioning IL-6 and IL-6Rα, it is likely that this antibody might be involved in the immune response pathway, possibly targeting components like interleukin-6 (IL-6) or its receptor. This suggests its participation in pathways that modulate inflammation or immune signaling. + +3. **Interactions with Other Molecules:** + - The context suggests interaction or targeting of the IL-6 or IL-6 receptor (IL-6Rα), indicating that this antibody might bind to these molecules, influencing inflammatory processes or immune responses. + +4. **Importance in the Biological System Being Modeled:** + - The system described seems to focus on understanding therapeutic strategies and modeling responses, possibly related to inflammatory diseases like inflammatory bowel diseases (IBDs) or conditions involving cytokines like IL-6. The antibody may be important for modulating these responses as part of a treatment strategy or for experimental observation. -4. **Importance in the Biological System Being Modeled**: The antibody's role appears to be significant in modulating inflammatory responses by targeting key molecular pathways involving IL-6 and its receptors. This indicates its potential therapeutic value in treating conditions where IL-6 is implicated, such as autoimmune or inflammatory diseases. +### General Inference: +- In systems biology, antibodies such as the one referred to, are often used experimentally or therapeutically to modulate biological pathways for research or treatment, particularly in immune response pathways dealing with cytokines. The context of IL-6 pathway targeting implies its significance in diseases managed by controlling inflammation, such as autoimmune or chronic inflammatory diseases. -In summary, while the antibody 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)' is not directly described in the context, inferred information suggests it likely functions as an IL-6 pathway inhibitor in an inflammatory response model, emphasizing its role in treatment strategies aimed at modulating immune responses." +This inferred summary is based on typical roles and interactions of antibodies in biological research and therapeutic contexts, especially within the immune signaling pathways referenced in the context." From bf55ede5e45f6b96de121753c762600e77d4e0a7 Mon Sep 17 00:00:00 2001 From: Inigo Date: Fri, 7 Mar 2025 13:02:29 +0000 Subject: [PATCH 12/14] Fix --- notebook/embeddings_and_evaluation.ipynb | 867 ++++++++++++++++++++--- 1 file changed, 766 insertions(+), 101 deletions(-) diff --git a/notebook/embeddings_and_evaluation.ipynb b/notebook/embeddings_and_evaluation.ipynb index 1a44959e..ba041bb8 100644 --- a/notebook/embeddings_and_evaluation.ipynb +++ b/notebook/embeddings_and_evaluation.ipynb @@ -1,11 +1,37 @@ { "cells": [ + { + "cell_type": "markdown", + "id": "dd85cafd-bdc5-4aff-8224-89186cf32cb4", + "metadata": {}, + "source": [ + "# Model embeddings and similarity assignment\n", + "\n", + "This notebook \n", + "\n", + "**What this notebook does:**\n", + "1. Loads a .csv containing species name and their backgrounds\n", + "2. Loads a subgraph with nodes meant to be specific to the model.\n", + "3. Generates embeddings on each side using a pre-trained BERT model\n", + "4. We compare embeddings from the species name/background to the node's enriched feature in the KG\n", + "5. We keep the best node in the graph and extract the code within the KG." + ] + }, { "cell_type": "code", - "execution_count": 20, + "execution_count": 1, "id": "d351ee6b-d9da-493b-b072-1dc8380307f3", "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/oneai/miniconda3/envs/py311/lib/python3.11/site-packages/tqdm/auto.py:21: TqdmWarning: IProgress not found. Please update jupyter and ipywidgets. See https://ipywidgets.readthedocs.io/en/stable/user_install.html\n", + " from .autonotebook import tqdm as notebook_tqdm\n" + ] + } + ], "source": [ "# Import necessary libraries\n", "import os\n", @@ -16,11 +42,6 @@ "from tqdm import tqdm\n", "from torch_geometric.utils import from_networkx\n", "import sys\n", - "sys.path.append('..')\n", - "from aiagents4pharma.talk2knowledgegraphs.datasets.primekg import PrimeKG\n", - "from aiagents4pharma.talk2knowledgegraphs.datasets.starkqa_primekg import StarkQAPrimeKG\n", - "from aiagents4pharma.talk2knowledgegraphs.utils.embeddings.ollama import EmbeddingWithOllama\n", - "from aiagents4pharma.talk2knowledgegraphs.utils import kg_utils\n", "\n", "import matplotlib.pyplot as plt\n", "\n", @@ -31,7 +52,18 @@ }, { "cell_type": "code", - "execution_count": 21, + "execution_count": 17, + "id": "987958fe-b489-44b9-a861-4a5b17530380", + "metadata": {}, + "outputs": [], + "source": [ + "sys.path.append('../')\n", + "from aiagents4pharma.talk2knowledgegraphs.datasets.primekg import PrimeKG" + ] + }, + { + "cell_type": "code", + "execution_count": 2, "id": "f724e7f5-1dbf-45cb-a60d-f48180b7adab", "metadata": {}, "outputs": [], @@ -41,7 +73,7 @@ }, { "cell_type": "code", - "execution_count": 22, + "execution_count": 3, "id": "a6619d22-6e3e-4167-9231-acfd5a69eeaa", "metadata": {}, "outputs": [ @@ -51,7 +83,7 @@ "Data(x=[3426, 768], edge_index=[2, 12752], edge_attr=[12752, 768], node_id=[3426], node_name=[3426], node_type=[3426], enriched_node=[3426], key=[12752], head_id=[12752], head_name=[12752], tail_id=[12752], tail_name=[12752], edge_type=[12752], enriched_edge=[12752])" ] }, - "execution_count": 22, + "execution_count": 3, "metadata": {}, "output_type": "execute_result" } @@ -65,7 +97,7 @@ }, { "cell_type": "code", - "execution_count": 23, + "execution_count": 4, "id": "d62c7c8d-760f-44d3-9c37-ddafbd45fd3e", "metadata": {}, "outputs": [], @@ -97,13 +129,13 @@ }, { "cell_type": "code", - "execution_count": 24, + "execution_count": 5, "id": "53dea1e5-24b8-4705-ac23-0ef1d6f7883e", "metadata": {}, "outputs": [ { "data": { - "image/png": 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kZmZSsmRJjhw5kmc14tf061NQrVo1dHV1efDggWSGCOqlaI19/McIB97e3hw7doy5c+dSokQJypQpQ5UqVT5ZPz8FkydP5syZMzRv3hw7OztevnzJ4sWLsbW1lXQqypYtS5EiRVi6dCmmpqYYGxtTpUqVfHUYNPz444/Ex8cTHR0NwN69eyXb/6FDh0oml99++y3btm2jbt26DB8+nKSkJGbPno2Hh4fW82tra8uIESOYPXs2mZmZVKpUiV27dnH27Fk2btz4m7c/Jk6cSN26dfOkf/bZZ9StW5dx48YRERGBl5cXR44cYffu3YwYMULSMVCpVHTu3JnFixeTkJBA9erVOX78eL4raDNnzuTkyZNUqVKF/v374+rqyps3bwgKCuLYsWOSoNaoUSOKFStGjRo1sLGx4d69e/z44480b948jw6EjIxsyiiTh4MHD4o+ffoIZ2dnYWJiIvT19YWjo6MYOnSoePHihVbZlJQU0bdvX2FmZiZMTU1Fhw4dxMuXLws0O7x7965o3769MDU1Febm5mLIkCEiNTVVq83k5GQxePBgYWFhIUxMTETr1q3FgwcPBCBmzpyZp838zOWioqJEmzZtRJEiRYSZmZnw8/MT0dHRv6tfgBg8eHCec9nZ2eVrWpgflSpVEoC4fPmyVl8BUapUqTzl8zNlvH//vqhVq5YwMjISgHTugsYjPxPE/OjZs6cwNjYuML8gU8bcpnoajh8/Llq1aiVKlCgh9PX1RYkSJUTnzp3Fw4cPtcrt3r1buLq6Cl1d3Y8ya9SYTub39+713b59WzRq1EgUKlRIFClSRHTt2lU8f/48T5vZ2dli+vTpws7OTujr6ws3NzexYcOG9/ZDw/uewdq1awsgz/gkJiaKkSNHihIlSgg9PT3h5OQkZs+eLXJycrTKpaamimHDhomiRYsKY2Nj8dlnn4nIyMg8z7AQQrx48UIMHjxYlCpVSujp6YlixYqJ+vXri+XLl0tlli1bJmrVqiWKFi0qDAwMRNmyZcWYMWNEQkLCR12rzH8LhRB/kJaSjMwnJDg4mAoVKrBhwwa6du36ydr19/dn0qRJxMbGYmlp+cnalZGRkfknI+scyPztyM9GfP78+SiVyo9S2JORkZGR+X3IOgcyfzu+//57rl+/Tt26ddHV1eXgwYMcPHiQAQMGUKpUqb+6ezIyMjL/emThQOZvR/Xq1Tl69ChTpkwhKSmJ0qVL4+/vz7hx4/7qrsnIyMj8J5B1DmRkZGRkZGS0kHUOZGRkZGRkZLSQhQMZGRkZGRkZLWThQEZGRkZGRkYLWTiQkZGRkZGR0UIWDmRkZGRkZGS0kIUDGRkZGRkZGS1k4UBGRkZGRkZGC1k4kJGRkZGRkdFCFg5kZGRkZGRktJCFAxkZGRkZGRktZOFARkZGRkZGRgtZOJCRkZGRkZHRQhYOZGRkZGRkZLSQhQMZGRkZGRkZLWThQEZGRkZGRkYLWTiQkZGRkZGR0UIWDmRkZGRkZGS0kIUDGRkZGRkZGS1k4UBGRkZGRkZGC1k4kJGRkZGRkdFCFg5kZGTeS2aOIDkzh8wc8Vd3RUZG5k9C96/ugIyMzN+TyKRMrr5M5VFCBgJQAE5m+lS2NsLWRO+v7l6BZOYIMrIF+joK9JSKv7o7MjL/SOSVAxmZvwlZWVlMmjQJZ2dn3N3dUalUDBgwgEuXLlG6dGni4+Olsn5+fkycOBGAsLAw2rdvT5kyZfD29qZy5cqsXLkSAH9/f6ysrFCpVLi4uNCyZUtevHghtdO7d2/KlSuHl5cXNWrU4OrVqwAExaay8VECof8XDAAEEJqQwfqH8VSoWoMnT54AMG7cODw8PFCpVKhUKjZv3iy1n5KSQufOnXF0dKRcuXJs375d65oXL16Mi4sLHh4eeHl5kZaWppV/7949ChUqxIgRI6S0H3/8kenTp+cZv8ikTHY8fsvckNcsuv2GuSGv2fH4LVFJmb/qPsjIyMjCgYzM34a+ffty7do1Ll68yO3bt7lx4wYNGzbE2tqaLl26MGTIEAA2btxIaGgo48eP5/nz59SsWZPGjRsTHh7O9evXOXz4MFlZWVK7Xbt2JTg4mDt37mBoaMikSZOkvDZt2nD37l1CQkL45ptv8PPzIzIpkyNRyQDkvNPHHODW0d3oFrNHp2gJANavX09GRgYAycnJ9O7dm6CgIHR0dHBwcODw4cOYmZnh7+/PoEGDeP36NSdPnkShUDB//nwuXbrErVu3OHbsGNOnT5eEGWdnZ2rWrEnTpk21+mBgYMC4ceM4ePCglPZrhJlVq1bh4eGBrq4u8+fP12r7fXnffvstzs7OeHl54ePjw+HDh6W8hQsX4u7ujoeHB56enmzYsEHK27dvHwMGDCjwvsvI/B2RhQMZmb8BoaGhbNu2jdWrV2Nubg6AQqHAz88PBwcHJk+eTEhICIsWLWL06NGsXbsWPT09fvrpJ3x9fenfv7/Ulrm5OZ9//nmecyiVSurWrSt9JAFatmyJrq56d7Fq1ao8e/aMS9GJ7/1huBK4jgpN2nH1ZarU7pYtWwgODmbZsmWkpaWRkJCAqakpRYsW5cCBA4wbN47hw4dTp04ddu7cSUBAAGZmZhgaGmJmZgaAlZUVSqVSEmbat29P6dKlefr0qdb5165dS8mSJSUh59cKM97e3mzdupUuXbrkubb35fn6+nLjxg1CQkIICAigQ4cOJCerz+vm5sb58+e5desW+/fvZ8SIEYSFhQHQokULrl+/zqNHj94zqjIyfy9k4UBG5m9AUFAQTk5OWFpa5puvr6/P8uXLGTZsGF988QWenp4AXL9+nWrVqn3UOdLT09m3bx8dO3bMN3/BggU0adqMx8k5eT6yGrIzM3kScoWSHhV5mJAhKSn+/PPPlC9fns8++wwHBweuX78OwNOnT7Gzs6NJkya8evUKGxsbHj58yP79+1EoFISFheHt7Y2Pjw8LFy6UznP58mUuXbpE//79tbZTHjx4QHh4OGPGjOH69eu8ffuWqy9Tf5Uw4+XlhYuLC0pl3lrvy2vatClGRkYAeHh4IIQgNjYWgPr160tCTqlSpShWrBiRkZFS3Q4dOkhbPTIy/wRk4UDmX8F/QaN+586d2NraEhwc/Kvqbdy4EZVKhaWlJXFxcXTo0CFPmQ0bNrB161YWLF7K+0YwOf41CqUOBoVMEEBGtrp0ly5dePDgAWvXriUiIoJatWpp1du0aROlS5fGyMiI27dv07hxY7Kzs3FwcKBhw4bsPXCQJUuXcf/BAzIzMxk0aBA//vgj+/fvx93dXWonICCA7t274+LigqmpKRt/3sSjhIxfLcz8XlavXo2DgwN2dnZ58o4dO0ZcXByVKlWS0qpVq8bx48c/ybllZP4MZOFA5qOwt7fH2dlZay/bx8eHU6dO4e/vr6UwpuHUqVMYGRmhUqnw9PSkSpUqXLp0Scp/V1muY8eOxMXFAWpFOU9PT1QqFZUqVSrwhzW3EtoPV6Mo416BjTefEZWUyfTp0ylfvjxKpZJdu3Zp1StIEQ9+u4Jdr169KFmypFRvzJgxUt6XX37Jzz//XOD4VqxYkUePHvH69et888+fP8/WrVu5ceMGERERbNy4EVAvg1+8eLHAduEXnYMnT56Qnp4uKTJq2LJlC5MmTeLo0aOUKlGM9+n36xsWIjszHSEECkBfR126Y8eOqFQq5s6di4eHB9evXycxMZHMzExq1arFjh072LNnDxEREdy5c4c+ffpQunRpenwxhBVr1rHmaQ5WPnW5/CCCtRs2EhISgqurK8ePH+fkyZOsWrWK7t27s27dOnr37k1aWhq2trasWrXqNwkzv4fjx48zadIktmzZgkKhPVq3bt2id+/ebNmyBWNjYym9WLFiREVF/e5zy8j8aQgZmY/Azs5O2Nvbi6VLl0pp3t7e4uTJk2LixIli+PDheeqcPHlSeHl5SceLFi0SLi4u0nHuellZWaJNmzZi1KhRQggh4uLipHJBQUHC3NxcZGdna7V//WWKmBEUK2YFxYoZQbGiybDvRIMvvpaO1x0+LcLCwkTt2rXFzp07teru3r1bZGZmCiGE2Lt3r7Czs5Pycp87KipKmJqaitjYWCGEEJMmTRI9e/YUQgjx+PFjYWVlJV69eiWEEKJnz55i3rx5+Y7fixcvhJOTk8jKyso3XwghunXrJlq1aiWdPycnR2zfvl3cvn1bODo6ikOHDgkhhAgODhY2NjYiJiZGREdHC2tra7Fq1Sqt/mvu07v3JigoSBgbG4vo6GhhZ2cnZs2aJUxNTcWECROkMoFhCWJWUKzoNGO5KF7OTdiUdRY2ZZ1Fs5GTxIygWFGkmK3oOGWx0DcwFF5eXkJXV1e4u7uLixcvitDQUGFtbS2OHj0qTE1NBSBUKpU0Xubm5kJHR0eULl1amJqZCQNjU6Gjpy+6fL9alHRViaKly4py1euJGUGxou/Ir4SRkZEoVKiQsLS0FEZGRkJHR0fY2dmJIkWKCAMDAwEIM5sSolKbbmLq5WgxIyhW9F++S+gaGKr77ugiADHp/BMxMyhWpGVmidGjRws3NzdRuHBhUaVKFZGeni6EEOL58+eiUqVKIjMzs8B7eerUKVGqVCkRHBycJ+/OnTuidOnS4siRI3nyQkJChL29fYH3Xkbm74a8ciDz0fj7+zNlyhRSUlJ+U/369etrKcPlRkdHhwYNGvDgwQMAihQpIuUlJCTkKZ+fEtqVHetQNWkrHT+zckXfulS+58tPEU+zKpL73ElJSQghyMlRt7plyxZJ2a9MmTKSgt2HsLa2pmzZshw5cqTAMqtWrcLLy4sqVarg5uaGq6srR44cYfHixdStW5fGjRsD6n3xQYMGMXDgQIoXL865c+fYt28fZcqUwdPTk/r166Onl78fggoVKuDn5yeZAn777bdkZ2cTEBAgrXg46qSQA5jZlKD3j1sYse0sn6/az6Vtq3l87TzuDT4j8u4NHMuVIzg4GD09PWJiYqhTpw4dO3bkxx9/xNHRkYyMDOrUqcOjR49wcHCgcePGVK5cmS+//JJzd0IZc+g2rnWbYlS4CIH+Q7FXVSb1bTxFS5cFwLH7GHYcPUVmZiafffYZWVlZjBkzhoiICMqXL4+JiQmDBg2iZtNWJL2O5cqOddJ1WtmVZdjmU4zYeoYixWxJin1OOTN91q1eRVBQEEFBQbRu3RqFQsGCBQsAsLGxoXr16qxbty7PuAGcOXOG7t27s3v3bry8vLTy7t27R7NmzVi+fDkNGzbMU/fevXt56sjI/J2RnSDJfDReXl7UrVuXefPmMW7cuF9df/v27XTq1CnfvNTUVHbt2qWlXPf111+zbds24uLiCAwM1FIS0yihaQSB+OfPSEt6S9FSZaQyyv+X+xALFiygWbNmkrAAatO0n376iaioKFauXIm1tTXwi4KdBnt7ey1t+gULFrBq1SpKly7N1KlTUalUUp5m3/ld0zwNenp6TJo0ScvUsCC+++476f9OTk4EBgbmW87f31/Sx9A4BVq9ejUAe/fu5dq1a8yfPx+VSqW1NZRtnMphqkhjbGhaGCt7J+Kjn1Kj8wC2DO+ImbFaOc/a2pq5c+fSvXt3rl27Bqh9L2RkZPDTTz/RuXNn5s6dS40aNShRogSzZ8/m6stUDAwM6TD5J5Lj3zCrWQV09PSxLlNOWqpXAqnFnenatSsRERFkZWXx5ZdfcvfuXV68eEH79u0ZOHAgdevVp/m4uZxZ9yPVOvbNMwbuDT7jwcWTDKtfgZkhIVhYWODg4CBtYV27do0GDRpQoUIFTE1N+fzzz9HT02PXrl3MmTOHvXv3UqFCBfr27Ut6ejq9e/eW2l6/fj0eHh4MGzaMhIQExo4dy9ixYwGYNWuWJNAdOnSI9u3bf/C+ysj8XZCFA5lfxZQpU6hcuXK+pnL58eDBA1QqFc+fPycrK4vLly9r5W/cuJHTp08DULt2bb7++mspb+bMmcycOZNjx47x1Vdfcf78efT19cnMEZLXPg0JL6IxsbDSajsHePhOuXfRKOKdOXNGK33YsGEMGzaMkJAQunXrRqNGjShatOh7r3XatGkUL14cpVLJzp07adq0KY8ePcLExARQ7zvfvXv3vW18Sn6Ph8MKlkZYGepy9WUqDxMyeP74AZG3rjF65gKaejli1K0LW7duBSAiIoIpU6ZoCX4PHjygcuXKuLq60rdvXwICAqhfvz5v3rwhM0dwIOS1dF+Mi1gw+cITVg5sS62eQ3Cp1Qj45f4tD1hF8yaNWbBgAUWLFuXatWtUr14dOzs7PD09ef0qlsDzQez5/pmkRPU6KoJFXeqhVOrgUrspYUe2UXLGV3h7e7Ns2TLu3r2LkZER3bt358CBA1SoUAGAiRMnMmfOHGJiYihcuLDWmLzPFPHo0aMF5r169Yrr16+zbNmy9465jMzfCXlbQeZXYW9vT5cuXZg6depHlS9fvjzBwcFERkbSpk0bunbtihC/fK67du3KjRs3uHHjBvPnz5dMxXLToEEDEhMTuXXrFqBWKnv3g69vZERWRnqeugIoSEE9tyKejY1NvmW8vLwoWbIkp06dAqB06dJaWyMRERGULl0agJIlS0qrG23atKFw4cLSNgmoV0IOHDyIl0pF+fLlmTlzptSGjo6OtKyvUqmoUqWKlJd7myM/ateujaOjo9a4vs8p0Oz95/Ft2ARQf/D27NnD7NmzUalU2NvbY2FhQcuWLWlarSJd3GyYWM2WBX6+ZKUm80VtDwplJFK7dm0ePHiAgYEBenp6TJ48mRYtWkjnHzFihGRl0LVrVw4cOCDN1PO7fwAJL6MxKaot4Akg9HEE586do2vXrgA0btwYCwsLrXIu5oYY6ypxMtOnpLMn3xy8ybCfT/Dd8p+JPLOXxnVr8+zZM3r16kWTJk2oXbs2tWvXply5clorRrq6upibmxMdHf3eMf8Qua1nwsLCWLp0Kfr6+r+rTRmZPxN55UDmVzN+/HhcXFwK3NfODz09PRYsWEC5cuXYtWsXbdq0KbBsZmYmT548wdHREYArV67w8uVLHBwcALWGvAK0PjCWdo4kvYklMy0VPcNfBAwFkJ97/a1btzJ+/HiOHTsmfdw13L17F1dXV0C9PH7jxg3p2M/Pj6VLl1K1alXCw8M5deoUixcvBiAqKgpbW1sALl26xOvXr3F0dJRm8MnpGVRu15MWIydhkfqK0U2rUK9ePaytrTE1Nf3VJoqg/rg/evQIc3NzTp8+TZ06dT7oFOjQoqnU6T2ciMlDcXJyomXLltK2wpAhQ1AoFCxatAiA6Oho6tWrxzfffENsbCynT5+WPsylS5fm4cOHCCFo0aIFnTp1Ii0tjVevXvH06VPWrl3LsWPHAPU93bhxI0OGDMn3/gHoGRqRla7tPlkB/Lx+Da1atdISCEqXLi05GQK19Un8m9dMalsLAQgBFhbmnDp5kldduxAdHS3dG39/f/z9/QHYvHkzbm5uWudMS0vLV0j9GPJdrbFyobL1b2tPRuavQl45kPnVWFpaMmzYMGJiYqS0gIAAbG1tpb+5c+fmqVeoUCGmTZuGv7+/1iz3XTIzM+nZs6cUX2DkyJFs375d8hyop1TgZKav9fDqGRjiVLUOYVfPSmknV/7A9828uHTxIv369aNo0aJ4eXmhUqno2LEjkZGReHh4YGRkhJGREQqFAg8PD6pVq0ahQoVQqVS0b9+ehIQE5syZA6iVKnfv3o2BgQHlypUjKSmJBg0aoFKpqFu3LnZ2dhgZGVG/fn1MTEwY5T+NDQ/jeRSfTlZ6OmUr+SKAOCNLzEo7cuqWeqk6NTVVMpmcNm2atILQrFkzEhISGDVqFAAnTpyQluvd3Nzo3r07Xbt2pV+/fgQEBDB79mxqVPRiXrsarB/dk9REtTJnZnoai7rU50XoPV6GPaBsxWqkv2PWl5aWxsaNG+nbV71vHxMTQ/369Rk7diw9e/YkICBAygMoXLgwurq66OnpsWLFCjIyMggMDGTdunW0bt2aBg0asGTJEiIiIti+fTsBAQEF3j+AYk6uvHoSKh0rAUdTXdatWaN1XoB27dqxZ88eoqKi8Pf3586dO9I2gIe7O6dOnmDrli1069aNSZMmsXv3bipWrMikSZOIi4tjzZo1mJqa0rt3b54+fUrdunV5+PAhL168QKFQUKpUqQ/GfXiX6y9TqOXry9V7YQjg2q6NzOtQC79yFnzuP4sbr37Rf3mfK+bBgwdrrSIZGhpqOYjSPC+urq5aOi2gfg+dnJwoW7Ys/fv3JzNTHVfi5s2bBeq6yMjky19qKyEj8xt5mpghZvzfZFHzN2jdYVG+ZkOttMjEDCGEENHR0aJo0aIiIiJCauP69esiJydHOga0zBiFEGLFihWiVq1aokiRIiIxMVErb/Xq1aJVq1ZaaW/fvpVMLkNfJwlbtwqi25w1oteizULPqJAYuumEmBEUK0YGXhAWtvZi3PF7YvfxMwIQnp6ewsvLS3h5eYkuXboIIYS4f/++UCgU4tq1a0IItSliWFiYEEKIpKQkoaenJ6ZPny5iY2NFoUKFRLly5cWks+FiRlCsaDjoa1HVr7c0Fs1HTxEutZsK9/ot1CaJxUuJK9eDRM+ePYWZmZkwNzcXenp6omTJkmLr1q2iX79+olChQsLLy0s4OjoKXV1dsWLFCiFEXjPV8ePHC5VKJTw9PYWzs7PYs2ePmDRpkhg9erQQQojMzExhbW0trl+/XuD96zFvg3Bv8JlW2oZd+4W9vb3WfdKwfPlyYWJiIgoVKiS6du0qMjIyRE5OjujTp48oW7asMDAwEFZWVmLChAkiJydHJCcniylTpghnZ2dRokQJYWJiIpYsWSKEEGL06NGiadOmYs2aNaJv375i165donr16iI+Pl4IIcTLly/fa4b6NDFDdJ65Qvi06iL1fdjmk2Lk9vOiQvMOovnoKVrP44EDB0RKSooQQm2aWrhwYZGUlJSn3ZiYGGFoaChiYmK00ocOHSr69eundQ8eP34sihcvLmJiYkROTo747LPPxI8//ijlt2rVShw/frzAa5CRyY28ciDzj6SUiR6NS6mdzGge4lLuFXGv15zM5CQAGpcylhTvXrx4gY6OjtbSdMWKFfM4sXmXgIAAxo4dS61atdiyZcsH+2VqairpHVyMjCM7IwMUCtKT3lKocBE2fd2fuW2rM799Dap36kdhc0tWbtyCgYEBISEhBAcHExwcLDk5Onr0KAqFAm9vb0BtiqjZXjlx4gQWFhakp6djaWlJ2bJlsbAsir6xWgGyfI0G3DiwTeqbV+M2hF09g7G52kXz2P1BuHp4sWbNGuLj46lQoQLz588nKioKPz8/VqxYQXJyMsHBwdSqVYuRI0fSr18/AOrUqSNtg2iUOg8dOkRISAj37t3js88+03L8o6ury4sXL6hYsWKB96+8b0Pinj3l7Yto6f51bdWM8PDwfO9T3bp1yc7O5smTJ2zYsAE9PT0UCgUBAQF88803eHp68vLlSyZPnoxCoaBQoUKMHz+ee/fuMW3aNOrXry8p1mrMbFeuXMno0aOZPXs2EydO1Ir7oKOjU+B9v/oylSuB6/Bq0k5KK17OHWuHciiUv1hfaKxn3ueKOTdr166lcePGFCtWTEo7duwYz549k3QwNGzfvp2WLVtSrFgxFAoFn3/+OZs2bZLyO3fuLCtFynw0ss6BzD8KHx8fLS+NmTmComXK09x/MQKo1Lor5cz0qfSORr6npyc1a9bEzs6O2rVrU716dbp06ULJkiULPNfdu3eJjIykcePGZGVlMXPmzDzL2/lx4cIFBgwcyIOHj6jSvheudZqiUCg4uHAKnWeuoER5D0Ivn2btiG6UreRLyLUrBX54tmzZUqAi208//cTLly9ZtmwZa9asISEhgZSUFOq/eoFxUWuCDwaSnpxESkIchczMMbW0QVdPn6TXLwG0PByGh4dz6dKlfE0ik5KS2Lp1q5YXydz9mzRpEsePH8+j1Pmhvft3LSKUSiVtxv2AydsYutV0+aBFxfviUfyamBM5OTns3LmTFi1aSLEV7t69y7Vr15g0aRLp6en06NGDYcOG5Vs/M0dw/1UyT0KuUMqjYsHnAcmFs14uRZj3uWJetWqVtKUFEB8fz1dffcWhQ4fyWL58yMy2WrVqDB48+IPjISMDsnAg8w9DY0f/Lpk5goxsIdnyv4tSqSQwMJD79+9z+vRpDh48yLRp07h27Zqk+PguAQEB9OjRAx0dHZo1a8bAgQO5d+8eLi4u7+1j9erVuRwUwoyzD9n4ZW8igi5Sxru6VhnHKrWp0r4XRxbPIPH1y3xnxk+ePOHatWv5Kn6GhoZy9OhRpkyZIvmcyMnJwdzcnLWD2qEwNMa1bjP1tev88pqbFLUm9kkoStRmjZqxWrVqFW3atMnXMmLLli14eXnh7Oyslf4+pU7I3/HP5MmT2bFjR56ym7dtp5S9A/pe9fK9f38EJ0+eRKVS8fTpUywsLLh8+bJkrpqVlUV4eDhnzpwhLi6O2rVr4+DgoGWRoSEjW5CUy03z+9C4cNZco8YVs2aFKDdnz54lMTGRZs2aSWlDhgzh22+/xdra+lebxRYrVozXr1+TlpaGoaHhr6or899D3laQ+Vegp1RgrKf84IfF2dmZgQMHsmvXLqpWrcqePXvyLZeZmcn69etZu3Yt9vb2ODo6kpKSIinVfQh9HQWm5paUr9mAW8fyP0f9/qOJCL6Mjq4uKSkpWkpoKpWKpUuX0rBhQ5KSkrSUPStXrkz9+vVxdnbWckalVCrp27cvDRo0YNC6wzh418DMpgSGJqZSGR09PVLi40hKiKPS/zXoc3JyWJOP0p+GdxURNXTt2pW0tDRatWol9VkTG0IIwfHjx/NYpXz33XfS1knuP2cnx4+6f7l5XzwKb29vrTge+VG3bl2Cg4OJioqiXLlyDBo0SMorXbo0nTt3RkdHB0tLS5o1a1Zge/o6CgxyxZx4H7lXa06fPk3v3r3Zu3cv5cuXz1M2ICCAnj17aq0qnTt3ji+//BJ7e3s6derE3bt3pbrvM7MF9UqOjo6ObFIp81HIwoHMf4Jnz55x/vx56TguLo7w8HDKli2bb/k9e/ZQxsGBhxGRPHocTkREBJcuXWL9+vWSBnh+3L9/n5ycHPSUCmx10nlw9ijFnNSmcmP3B1GivIdU1qhwEfxPPsS9YmWWL1+u9bEMCgri559/ZtiwYeTk5BAVFUVUVBT3799HT0+Pvn37cufOnTznHzNmDKuX/EitogqOLp1F7Z5DpLyc7GzePHtCFb/evD21TVq2VyqVREZGUrdu3Xyv6cKFC1peATVkZmYSGRmp1W/NzPvw4cNUrlw536XyT4WjoyPt2rWjb9++UlhnIQSBgYFUq1aN+Ph4pkyZQnZ2NqDW8H9X6x/UVjQrV67kwIED3LhxA1BHmTx06JBU79SpUwW6P9ZTKvCwtaSwVXFeR4YX2F8lUO7/qzXvc8UM8PbtW7Zv306fPn200iMiIqS/zZs34+rqKvnS0FhwPH/+HCEES5cu1XJMde/ePdzd3fMNRy0j8y7yUyLznyArK4vJkydTrlw5VCoVvr6+9OzZk1atWuUpG5mUybRFy7Cp3YpFt98wN+Q1Ox6/xbSUIyVLlmTv3r0FnmfLli24u7vj5eXF5E6NKFu5FpXadCuwfA7Qo5OflikbqJXOlEol9evX10pfsGABV65cYceOHdJsfdq0aVJ+o0aNcHNzo2f9qrSqX4ueAwZJURafBF+ivGdFlk//jvI25h8etN9BQkIC33///R96Dig4HkWJEiU4ffo0YWFhODo64uHhQZUqVQqMC1KiRAm+/PJLyS31qFGjePHiBa6urvj4+NC0aVP8/PwK7EclayPcG3zGo4snpbTrezYxo4knt47u5fiy2Uxr4olRzH0ALVfMmvuocfIFav8L3t7eODk5ffRYODg4MGnSJGrUqIGjoyNWVlYMHDhQypddOMv8GhTiQ+tgMjJ/Mvb29hgYGGBoaEhycjJubm6MHTuW6tWrs2bNGoYPH06ZMr/EUKhRowY//fRTvnkrV67Ex8eHx48f4+joyKRJk5gwYYLW+U6fPs2XX35JSkoKqVk5NP5mLmW8Kmk5ENLEGGhcypgKlkZ8+eWX+Pj4SDOz3G0IIQgICKBatWpMWrScGd9+iUUJ9fKuUeEi9F++CyVwfOVcIk7vw1BHwaNHj1AqlQwYMIC5c+dy8+ZNxo4dy8GDB3/1+AUHB9OrVy/pWOMUSKlUMPv77/MNDCTz+zkQ/JCB3ToxZN1hRC79gXefnb+CjIwMfHx8OHHiRL4KnDIy7yILBzJ/O+zt7dm1a5fk4GXHjh306dOHw4cPc+/ePXbt2sWuXbvy1FuzZk2BeePHj+fSpUs8fvyYsLAwSfkrOjqa6tWrc/DgQUxKObL2zksy09MwMjUrsH/1jZPo2boZd+7cQaFQaLXh4uJCeno6qampFClShDVr1rBp+w4+X7hBivOggDwWFRcvXqRx48acPHlSMlts3bo1w4YNo169eh9UuPwQaWlprF69mi+++OJX15X5eJZv3ILC3pM3hawKvNd/BQ8ePCAsLExLuVFG5n3I1goyfzkf+vC1bduWK1euMGfOHJo3b/6r28/OzmbNmjUcOXKEzp07c+LECWm5fvHixXTp0gUXFxd2PH6Lvr4BuvoGBbalBOYuWUm7du0kASN3GwAGBgYYGPzShpGuklsb5hO4YwdCgEKBtNQfGBhI2bJlefr0KQ4ODpJgAGq79Hk/LSHe3uc3BU/KjaGhoSwYfAJatmypZR4IYG5uzsmT6u2EAV07Ah9+pv9sypcvn6/So4xMQcjCgcxfRkFRA7PzWcuqUqUKe/bsoXnz5pIJmoaePXsycuRIAK08GxsbDh8+zOHDh7G1tc0TIRDUvgzs7Oyo36AB9yKfY1+hKk2GTUDfyFhqPzsri5MB87h5eAdKHV3ioiOp7VuD+Ph4MjIyWL9+PfHx8SxatIjs7Gy8vLw4duwY27ZtY+HChTx9+pSIiAiMCxVi5MiRODs7M3jwYF6+fEmrVq2oXLkyT548yWMRYFKuAidODML3/+MT8/A2h3+cRp+Fm3iYkME3Fa1wd3eXtNkXLVqEr68voA4lPGfOHLKzs7GxsWH16tWS5vqwYcPYs2cPT5484caNG1pjqdnS0fgn+Oabb+jYUf3B8/X1Zd26dVrbNv9UfuvHuyDrlnfRU/49hAIZmd/MX+WaUebPxc7OTlhZWYmMjAwp7cSJEwIQw4cPz9cV8Lsucl+8eCF69eolypQpI1QqlahQoYKYNm2aEEKITZs2CS8vL+Hm5ibc3NzEnDlz3tuf6y9TxIygWNHqqxmi8dDxYkZQrPhq33Xh4F1doFAIu7JOWuX9/f2FoaGhKFGihDA1NRVjxoyR3BQLIcTMmTNFiRIlROHChUWVKlXE5cuXpbwSJUoIMzMzAYiwsDBhZmYm3rx5I4QQonHjxsLc3FyUcXAQ1mXKCWuH8sK3+yAx+WKkKOHsKSaeDhMVWnQQzr6NxHenHokZQbGiaGkH4T91mrh9+7ZwdnYW5cqVExUqVBBv3rwR8fHxwtvbW4wePVqsXr1aNG3aVCQnJwshhLh7966wtbUVW7duFSEhIUIIIbKyskTz5s2Frq6ueP36tdTnp4kZYsrlZwIQky9GihlBsaJcjfpiwMo9knteQNyOfJlnbO/duydsbGxEdHS0EEKI9evXi2bNmkn5p0+fFpGRkcLOzk7cuHFDq25+aRp27twpunfv/t77+nfnaWKGCAxLEDP/P4Yzg2JFYFiC5NZYRkZGjWyt8B+idOnSWjOfgIAAfHx8PqpuamoqtWvXxs7OjkePHnHjxg3OnTuHsbF6hl2qVCkOHTrE7du3OX/+PEuWLJHCHL+LJmpgZloqZzYupXontUteA2NTGg76BuMiRUnOyiEq6ReTwYiICOrWrcu0adOoXbs2Fy5cYN26dYBaAW/x4sVMmDCBunXrMmTIEIYMUZvwxcbGEhsbS6FChQC1219NhECAhw8f4u3tzYNHoYwKPE+d3sN4eusaegaGVGjux+GfpnH72F7a+y/EqHARAPSNClGrZk0uXbqEqakpDRs2pEWLFpibm2NmZsakSZMkm3h9fX3p3C4uLjRr1oynT5/i6ekJgI6ODhkZGdja2mq5dr76MpWc9HSUOjro6OkTHxPFy7AHlKmo7fUvdzAfDbdv38bT05PixYsD0KxZMw4ePCj5A6hVq5YUofDX0Lx5cw4ePEhCQsKvrqvB3t4eZ2dnLS+XPj4+0rNy7NgxfH19KVu2LD4+PtSvX5+zZ9XBtOrUqUOZMmW0glLlpqBgRBreDWN9YfNKTq5eQGhCBiPmLKG8u6fUtqWlJW3btpXqzpo1S2q7atWqXLlyRcpbv349Xl5euLu7U79+fa1th0OHDuHj44OnpydVq1YlJCREyvPz8+PChQu/dShlZP5QZOHgP0Tv3r1ZtWoVoDY1u3TpEk2aNPmouj///DOmpqb4+/tLy9iFChVi+PDhgNpiQOP/3czMDGdnZyIiIvJt6+rLVJTArWN7sfOqLC3hFzIzx75CVfWmPL/4od+9ezc7d+5k4sSJgPqDqlKppPYVCgWZmZmkp6cDahezmo/funXraNu2LdHRan/9N2/elCIEhoaGkpycTGpqKjmZGTiZ6RN56zrF/++XwKtxG4IPBmJhWwZjc7X9vhIo7+pB2KOHkoveLl26cPLkSen8Bw8elGzXc0fye/HiBSdOnKBChQpSWmJiIidPnqRnz55SWmaO4FFCBs/DH2JT1hmlUsnj6xewdVPlGcuvO3+Gp5cXo0aNIjlZHabZy8uLoKAgHj58CKhjHwghtBzkvI8ePXrg4eFB3759tfz96+np4eHhIX2sfyvp6en5OpM6duwY3bt3Z9asWYSFhXHt2jWWLl3KixcvpDLz5s2TfCocOHBAq/7YsWOpUaNGvud8N4x1Zloq5/4vmOYAPq260Hv9Cfadu0pwcDDFihWTYhdohM8rV64QHBysJXzev3+fMWPGSIJx7969Jd2OuLg4unbtytq1a7l58yazZ8/Wiocwbtw4vv766988jjIyfySycPAfokaNGkRERBAdHc2mTZvw8/N7bzCZ3PwaX/V3797l4sWLNGjQIE+e5sOXA4RfP08p9/x90cdFRzKoSXUcHR0JCAjgwIEDVKlSBVC7nF22bBk///wzKpWK6dOnM3LkSL766isOHz7MvHnzWLRoEaBeHXk3QE3Dhg2Jjo5m7969ODg4kJWVRZEiRejuWYJXTx/TaIja66CppQ06enpkZaRLdfPzS1C9enVatmxJhQoV8PDw4NWrV5LvgcePH+Pm5oZKpaJhw4aMHDmSevXqAWrzsgYNGmBkZCQJPqB2ryuAhxdO4N7gMwDevozGxMJK6zrG7r/BkJ+Pc+z0OWJjYxkzZgwATk5OLF26lB49euDj48Pr168pUqQIurofVjE6c+YMN2/eJCgoCEtLSy2hBdAKpvRb8ff3Z8qUKXl8DmjMTKtX/8XVtJOT00fZ5hcUjEiDRiDV8K5gCr8ERrp8+TIvX76kZcuWwC/Cp0b4yi18vm+VJiwsjKJFi+LmphY2fX19efr0KUFBQQCoVCpiY2O5d+/eB6/v705mjiA5M4fMHNn47d+CLBz8x+jevTtr1qxh1apVdO/Vm4xsQY4QBUYn/FDUwneJioqiVatWLF26NN+la82HDyDhRTSmRa3ylOkycwXWZZwYvuUUIfcesmfPHumD0bZtW5ydnZk1axYPHz4kODiYmTNnsmPHDsLDw0lNTWXkyJGSEt3du3f57LPPtNrXRAi0s7PjypUrzJgxg9TUVLZv20Z8xAP0DQtJL0Zhq+LEx0SSGv8GUNuq92zfivDwcBwcHKTtgzFjxnD37l1u3brF5s2bpRgFrq6u3Llzh+DgYG7evCm56M3MzKRjx454enqSkJCgNc76OgqyMzO4c3wfVdr1AkDP0EhLSAEoUtwWBWBe2IRBgwZpzejbt2/PpUuXuHbtGl988QWpqakFxpDIjUZpUU9PjxEjRuRZJfhQMKWPwcvLi7p16zJv3jyt9I8RQEeOHCkt/f/000/AL8GIlixZkm+d3AKphvwEU01gpBUrV9K9e3cppoWXlxcjR46kTJky2Nraagmf71ulcXJy4vXr19LWwZ49e0hMTNRaUatWrRrHjx9/7zX/nYlMymTH47fMDXmt5TAs95agzD8TWTj4j9GjRw/mL1hIEnrsTbHgystUgmLTeJhlTPTLV1plX716hbW1NfBxvuqjo6Np0KAB48ePL9CbnL6OQjLj0zMqRGZ6er7lQNsPPaiX4Js0aUKrVq0YNWqUlB4YGIiHhwclSpQA1Nsn58+fJyMj4739LV26NCVLlpTcBjdt2hSRlUktg3iczPRRoN7hKFOxOoemj+IzK0EFSyMUCgUdOnTAxsbmo1305iYrK4tOnTphYWHB8uXL8whgekoFhd/G0HTYeGk7o5iTG7FPQqUyqW/jyUpNoZyZPjoItmzZorVdERMTA6jNOMeOHcvgwYMl3YeCSE5OltwQA2zatEmrTcg/mNJvYcqUKSxYsCDfuAjvI/e2gibCYO5gRPmRWyDVUJBgmp6azNYtW7QsR8LDw9mxYwehoaFERUVpCZ/vW6UxMzNj+/btfPPNN3h7e3PkyBFcXV21VnB+70qMRlBydXWVtttUKhV+fn6UK1eOI0eOSGXj4+Oxs7Pj0qVLrFmzhtatW0t5x44dk7xK3rp1i1q1auHs7Iy7uzt9+vQhNTWvbsu7OhwxD2+zelhnQhMy2PAogdOh0XTt2pVy5crh5uaW7xbKxIkTUSgUUvjvtLQ0WrduTbly5fDy8qJhw4aEhv7y3F+5coWqVatSoUIFXFxctLxwfvnll/z888+/eSxl3uGv1oj8t6DR8u7Zs6eYN29envwrV66IatWqCSMjozxWASkpKaJ79+6Spv9nn30mXr5Ua6GfPHlSGBoaCi8vL+Hh4SEqV64sLl68qFU/LCxMKBQKMXnyZK301atXi8KFCwsvLy+hp6cnqlevLvYFPRDtJi4Qg1YfEDOCYkX9AWNE9c4DxHcnHghjc0vx8/ELombNmuLBgweiSZMmokOHDsLd3V0olUphZWUlJk+eLLKysoQQQixZskQUL15c6OjoCH9/f+Hs7CxWrVolhBCiZ8+eokSJEsLLy0t4eXmJL7/8UurXomNBwsGnhjCxsBKFzMxFzW5fiGnXXogZQbFi3PF7opSHj9DVNxAly5YTPXr0ECkpKSIxMVG4uLgIb2/vPGMbGBgoXF1dRWJiohBCiM2bN4ty5crlKQeIuLg46TgnJ0e4ublJlgOXL18WRYsWFWlpaWLSpEnCw9NTKJVK4eLqKmxsbISBgYFwdHQUzs7OYsCAASIuLk7ExMSInj17Cnt7e+Hu7i48PDzEjBkzpPE3NDQUJUuWlP5GjhwpNmzYIADh6ekpjc+gQYO0+vo0MUOySpgRFCumXo4WRYqXEhNOPhQzgmLF56sPiGKOrsLF3UO4urqKbt26aVk7NGnSRLi4uAgHBwcxdOhQkZaWJuUNGDBAlCxZUujo6Ahra2tRtmxZ6TlSqVTCw8NDuLu7i5YtW4rw8HCpXnh4uHBychI5OTl5xrYgMrJzRFJGtsjIVtfJbQ0xfPhwMWLECOHt7S1OnjwpatasKX766acC26pdu7bYuXNnnnQ7Ozvpz8bGRujp6Wnd/4zsHMk6QfPnWreZ8Jv8k1bajKBY0d5/oahStapW+7Nnzxb9+/eXjpOSkgQg0tPT8/QlJiZGGBgYSBYquUlLSxNFihQRjx49ktJGjhwp/P39C7zm3NeQexzfJTw8XJiZmWmlXbhwQdjb24v4+HghhBDdunUT3377rRBCaFknbd++Xdja2orr168LIYR4+PChljVNhw4dxMSJE7Xafvf5zM+axrVuMzFu6kytscnN5cuXRdOmTbWeidTUVLF//37pGVu0aJGoXbu2VMfLy0vs3r1bCCHE69evhZWVlbhz544QQm1N5eTkJP0+yfw+ZD8HfxLFixdn/vz53LhxI49L3GXLlpGSksKtW7dQKBT079+f2bNnS1Jx+fLlJcn6xx9/pE+fPlrhWletWkW9evVYvXo148eP15qJ1q1bl127dmFvb49lyVKM/XIU3easydM/oyIWdJm1kmG9u5OV+Ib27dvTpEkTOnTogLGxMTNmzMDR0VHyVW9iYkJ6ejqdOnXi1atXHDp0iKdPn7JgwQIWLFjA06dPady4MZs2bcpzrr3zJuJatxmfjZnONv+hPLp0irIXjuPgXYPZLXzIyclG5OSQnZrE2bNnWb16NXFxcTx69Ag9PT1cXFwwMDDAz8+PcePG0aZNG65evYqPjw8GBgYYGxtrzSCaN28uaYm7ubnh5OTEqVOnUCgUrF27lv79+5OamoqBgQGBgYEYGBjw3XffUbt2baZMmcKxY8fee2/XrMk7ngC9evXScmOcm4L2xjWUMtGjcSljDkcmq5f39PSo1qEP++aM52XYfXJysjEki2JWNhw7dox69epx5swZaTaY+xk7duwYDRo0IDo6WrKo2LRpE76+vtIqi5eXFyYmJixfvpxKlSpJdRcvXsyiRYukrZhJkyZpPV+1a9fm2bNnPHr0SEpPTk6mZp26xCWlkp4tMLW0ps24OVRxcdTyYTF+/HhcXFyk5fsuXbowcuRIKlasSOnSpenduzePHj0iOzsbHx8frZWgR48e0bNnT169eoWVlRVr1qzBzc2N3bt306lTJ4yMjFCpVKSkpPD48WMCroTyQmHCk9tB7P3+W+JiIokIukTiqxfU7jUUgAPzJhJ27giTvh2rdS8cHBxYvXo1SUlJmJiYsG/fPsqVKydFN4yJiaF48eL5rtJo8kC9WlKvXj2t7Z179+5pxT94l4J8gXyME6xq1arRqVMnRo4cSevWrbl161YeRdBVq1YxdepUjh07JjlJyh3PQUdHh0qVKnH79m2tehodDs1WzbvWNK+ePubZ3WAqLN8o1dEoLAOkpKQwZMgQAgMDJd8coHbWldsKpWrVqsyZM0c6VigU0upWcnIy+vr6kpWPtbU1ZcuW5ciRIzRt2vS9YyPzYWTh4E9CE243vxjsCoWClJQUMjMzUSqVJCUl4eHhkU8rUL9+fcaO/eXH633e/3ITERHBuIDtXJ6hHVegwedfSf938FGH+O0+dS4Tu7fUKqdUKilcuHC+H8JevXrRsWNHLl68qJVWkElZIT0diuukUczJFWMzc2KfhFHY0gZ9o0JUbtON9NRklixdiqupksaNG2Nra8ugQYMYN24cs2bN4s2bN8yaNUtr/GbMmMGMGTPyPd/+/fvzTQf1dsnly5fzzVuyZInWWP/ZVLA0wspQl6svU3mYkIFHo1YcXz6bhYcv07xCeWxN9AgKCnqvXojGAiAwMFDS23j06JEkLLVp04YVK1agq6vLvn378PPzk/bEd+/ezcaNG7l06RJmZmZMnz6dfv36SW0/evSIR48eYW5uzunTp6lTpw4A95Kg9bytGBmbkAOc27CUvbPHUXTeepIyc7gfl4YKsLS0ZNiwYVKwo7179zJt2jS+/PJLoqKiUCqVlClThkmTJrF7926tqJoDBw5kwIAB9OrVi+3bt9OrVy+uXr2KmZmZljA9Z84cTp8+Tb1yJdn4KIGdU0fR4IuvsShRmq3fDebs+sU412rEmqGdaTDwK85tWIJSqcTHx4fExERMTEwoUaIEVatWxcfHBz09Pd68eYNSqcTFxQVdXV0UCgVZWVmkp6fTvHlzjI2NJedUT548QalUYmFhQbVq1dixYwfx8fEUKVKE5ORkbt26RYMGDRBC8NNPP7Fs2TIyMzMpVKgQ+oUt8OgyBKdKNaVtEQGEJmTwMCFDitWwb98+LSF89uzZrF27lpycHJycnAgLC2Pfvn0cO3ZMEmh27tzJnj17OHv2LMHBwZQqVSpfB1gtWrRg5cqV0ru1evVq+vTpQ/cf1uJaV/0R3/hVH6zLlNOypnkZ/pDC1iX4fuxwpkXcxrJoUWbNmiVtU3311Vd88cUXlCpV6r3vwIIFC7SCo61evZpWrVoxfvx4YmNjWbZsmZbQodHhkIWD34+sc/A3YODAgZiammJtbY2NjQ0JCQmSqdS7bN++XSsMa37e//IjLTOLw7sDKeHiWWA/sjMzeRJyBYWD5yfROl6wYAGenp60aNFC+rEGmD9/Puf272JeM08igi5SpmI1Sjh7ogD6j/4a3VeRNHUvg7W1NS4uLpLWOPx5ClxpaWnUrl37Tw1SFBwcLO0Za/5a1KxExO4ARnkVpbWVoIipCV1UdtKssWLFiu8VDj5kAdCyZUtpD7xq1ao8e/ZM8kEwe/ZsJk6ciJmZOs7Et99+K83yQT3r7NatG/369ZOeu8ikTI5Fp2Lwf8FACEFaciIKhYIc1GGrI4o4SgprEyZMQAiBg4MDd+7cYfTo0Zw7d46IiAgeP37M8ePHqVmzJlWqVMHZ2ZnWrVvz8uVLrl27Rrdu6miX7dq1IzIyktDQUOrUqaP1rAUEBNC3b19pJQaFgvTEBIo5uUp+K0z+/2+7Wj64ubkxYcIE1q1bx4MHD7h+/Tr+/v506NCB+/fv4+HhQdWqVbl//z737t1j7969ZGZmMnr0aMLCwqhVqxZHjx7l6tWrhISE8OrVK06ePEloaCjr16/Xujfr16+nV69emJiYMGHCBH7++WcOHjzI/fv32X3mMt79xvLqSaiWIiX8Mls/HJlMVFIm33zzjWQ+efToUVavXs3Fixe5e/culSpVwsrKiipVqki+Na5cuUJ4eDj6+vqYmpqyYcMGqe0tW7ZIOh1t2rShY8eONGrUiDZt2hAREcGKFSuoXKWqlg5H3b4jCdq3VcuaJicri6g7QXg2bsPZS1cZOXIkLVq0IDMzk6NHj/LkyZN8w4DnZvr06YSGhmoJ/TNnzmTGjBk8ffqUO3fuMG7cOK0J16ewppFRIwsHfwOOHDlCTk4Oz58/JyYmhiJFikizKVAHTVGpVBQrVowFCxbw7bffSnkBAQFSzPeuXbty4MAB4uLipHyNO+HKPj6gUNB85OQC+5Ec/xqFUgf9QiZk5OfD+Fcwbdo0wsLCGDZsGHfu3KFSpUp4eqqdzFSuXJmqVavyIiaaqMhI0sLv4Pb8OqO8ipJ06QAVPNyIiYkhOjqahw8fsnLlSqndP+vl/ytiEahUKumHOfffyJEj0VMqqOKtombNmtjZ2dGmTRtmz57Ns2fP3tvmrzFBXbBgAc2aNZOEhbt373Lt2jVq1KiBj4+PlqJldnY2a9euVc8iu3dn7969JCQkaJkMrvy8HdMbunH72B5afv3LSo/GZDA3p0+f1trOyE12djY//vijNIOMjIykePHiUj8VCgWlS5fOE/PgwoULxMXF0aJFC0C9ErN61SpOLJ3FzGYqnoZcpULT9lQsWwoTPSXO5oY8ffqUKlWq4OrqKrXj7e1N48aNefToEbt27WL58uWS8y97e3t++OEHJk2aBKitdSwsLDA0NATUljEFKXAqlUq++eYbkpKSmDNnDqtWrZIsfK6+TMXOrQJV2vfKt65mHNfuP06RIkWkeiEhIdSsWRNTU1NAbVp56dIlyWRZs5zfq1cvdHR0WLFiBWvXrmXq1KlabWusaYoXL86CBQvIycmhX79+LFq0CENDA3KLoyXKe5CZnkri6198YhQpbkth6+I4VqqJvo6Cpk2bkpGRwZMnTzhx4gRBQUHY29tjb29PVFQUzZo10wqFPmfOHHbs2MHBgwelLZpXr16xc+dOunTpAqi3e6pWraq1ovQprGlk1MjCwd+A5cuX06ZNGwwNDdHX16dr165SIBf4RecgMjKSNm3a0LVrV4QQxMbGsn//fqZMmYK9vT3e3t5a3v9ArXMQHBzM9Rs38PNfKGm/54e+YSGyM9NBCC0rgd9CyZIlUSqV9OvXTzL7W716NcHBwSQnJ+Pv7w+o9wmbN2vGpXNn0FMqWLx4MV27dkVHRwdTU1Pat2+vNRb/5ZdfqVQSGBjIhQsXaNKkCefPn8fNzU1Lm/u3smHDBrZu3cry5cultKysLMLDwzlz5gyHDh1i2bJl7Nu3D4ADBw5I3g4tLS1p0KAB6zds1DIZ7Lc0kG+O3MajUWtOBvxitqgxGcy9OhUVFYWNjU2efgkhGDRoEObm5pLDrY/lq6++IicnBx8fH2klplPzRnzRtxexzyK5cfM2EWf2UT4tCh2F2u/E27dvC2zvxo0bODk5UbSo9jtUrVo1IiMjiY2NpVOnTtLz3qNHD1atWpWvpj/AgAEDMDY25u7duxgYGODs7Azkb3qZHzn8X6iqXFlK8/b25tixYzx//hwhBBs3biQtLU3S19As52v26a2srDh16hQbN24kPj6eHj164O7ujpOTE4UKFZKsaebOnUuNGjXw9vZGARQvpKv18Sjp7En0g1u/HLt4YWhsin7MQ/SUCq5cuYIQglKlSjFjxgyePXtGREQEERER2NracuDAAcnkeO7cuWzatImjR49KJsGgDnBlbGzMiRMnALWwcPnyZdzd3aUyn8qaRkYWDv4WODg4cOTIEYQQCCHYv3+/1gOvQU9PjwULFhAVFcWuXbtYt24drVu3JjIyUnrRNN7/8tRVKnAy03/vDTc0LUxhq+IUjo/63UFjcs/uL126xOvXryVFLAcHBw4dOgSolYpOnjwpXW/uvMzMTA4fPiy//O/g7OzMwIED2bVrF1WrVn1vMCBvb28tXZD82LJlC5MmTeLo0aNaH+jSpUvTuXNndHR0sLS0lGahoF6xevjwoTT7O3v2LKtWrcpjMqhUKqncphs39m/VShegtTpVqFAhLW+SGoYNG0ZkZCRbtmxBqVQ/vaVKlSImJkba/hBC8PTpU8lHA0BSUhIhISGcOXNGWoE5duwYKSkpTJ48GT2lAvfyjnlmnoA06/8tFCtWjFu3brFx40Y8PDxYvHgx1atX/6BZbe6toYSkFBZ0qsO8djVY+Xm799ZLeBFNUatf7lndunX58ssvadGiBVWrVsXKSr3Ur1QqC1zOL1asGKdOncLa2po2bdowZswYnjx5wt69e6lQoQLOzs7MmTOH8ePHS3WczPS1hJdiTq6kxL8hJSFOuh6/ST+ybuIIPD09GTx4sKTs+z6ioqIYPXo08fHx1K1bF5VKJTk/09HRYevWrYwZMwYvLy9q1arFiBEjpJUxIQTHjx+nTZs27z2HzEfyF1lJ/OvIbcpoZmamZb62detWcf/+fVGyZElhbm4umbdpzLZev34t2rVrJ1xdXYWrq6to27atiI2NFULkDX4khBBr1qwRnp6ewtnZWezZs0crLzMzU1hbW4vr16/nCaaUn/nRu381u30hpvywQKqzevVqUbJkSVGoUCHpuoKCgj6YV79+feHu7i68vLxE1apVxYkTJ6Q2g4KCRPXq1aVr+OqrryTTpcePH4tGjRoJd3d34eLiIvr06SNSU1Olur169RLr16//nXfrn0lUVJQ4d+6cdPzmzRtRrlw5sWvXrgLN/A4fPiyKFy+uZf4aGhoqtm3bJoQQYsuWLcLR0VFERETkqTtt2jQxZswYIYTa3NbHx0ds3bpVPH/+XJiYmGiZhWZnZ4vixYuLYZtPim+P3JaCVM0IihUtvpwq7LwqaT1nM4NitczyTpw4IWrUqKF1/qFDh4omTZpomWFqqF27tli9erUQQoht27blMXFduXJlnvaysrKEubm5OH78uBBCiNjYWFGqVClx4cIF6f01NjbWMlvMzcOHD4WRkZF49eqVVvr+/ftFqVKl8q2TlpYmzMzMJDNB3jGnFUKIxMREYWBgIO7fvy+E+MX0sv/yXaJ4Obf3vq81ugwUEydNyvfcQghx8eJFYWtrK4QQ4uuvvxYlSpSQzD51dHRE8eLF8/yGCCFEdHS0MDExEUIIsXjxYlGsWDGpnoGBgbCyshLffD9fzAiKFbOCYkWNrp8Lxyq1RdPhE8Ws//ctKDalwH79ERw8eFB07dr1Tz3nvxlZOPiPERSbIr3QuX9kNMf7bzwQlSpV+lW27H8WsbGxwsPDI1/78nf5kF34P5GIiAjRqFEj4eTkJEXA1ETFrF27tihatKiWUHrhwgUhhBCHDh0SNWrUEGXLlhXu7u6iXr164uzZs0IIIXR1dYWtra3kb8HLy0v6+KWmpooePXoIFxcX4erqKiZMmCCEEGLWrFmibdu2efo3cuRI0azHQDFk3WFRvLy7KOboKmwcXYRrnaZizN5rWs/ajrAErboZGRnCzs5O8tVw7tw5AQhnZ2epX61bt5bK379/X1StWlU4OTkJb29vcfPmTa32qlWrJvncyM3Ro0dFxYoVhaenp3BxcRE//PCDEEIt3AcFBQkbGxvh4OAg7t27J9UJCgoShw8fFkII0aFDB9G2bVvJj0F4eLhwdnYWy5cvF0IIcfXqVREaGirVDQ4OFoUKFZL8luQnHAghxDfffCNq1qwpoqKihBBCBIYliF4LNr5XOJgVFCsGz/opzwdRE40zOTlZNGzYUCxcuDDP+TTXrPEvkJSUJF6+fiO9Mz/88IPw9fXNt15uQTQyMUPsCEsQ5arXE51nBYjW33wvdvxFUS43b94snj179qef99+KQgghO8P+jxH1f9vph7lsp8uZ6VPp/7bTgYGBVKlS5TdF7vsjuXz5MtnZ2Vqa9+/ye+zCZX4/kUmZbHz04aiN3ZzM8tyP2bNnA0gxIv5M7O3tGTNmDBcvXqRZs2b88MMPJCUloaurS9myZZkxYwZubm6kp6czfvx4duzYgb6+Pjo6OowaNUpSCj58+DATJ04kPj4eIyMjdHR0mDBhgqRMqVAoKFGihNY2QlRUFEIIFi5cyMqVK8nMzMTUvCgJCgNqdBlA+Rp5Y5RoaFokg9b1ahAaGiopHXp4eJCTk0NGRgbdu3dnwoQJ+Vq02Nvbs2vXLoo6urH32l2mft4NkZ2DQFDavgwL5s+nmtsvPg+Cg4Pp1asXoaGhWFlZSVYsnTt3ZtGiRVy/dRcLM9PfvSUp8/dAFg7+g7Rs2ZKnT58iACHULoItzM21FP8+htx20RkZGQwePJjmzZtTtmxZPDw80Dxa06dPp3nz5oDaYdDw4cNxcHAgLS0NfX192rZty1dffSUpGtrb25OSksKzZ88k07mTJ09Sr149hg8fzvz584mIiKBXr17cuHGDMmXKEBwcTFBsKkeikrWcswDSceNSxpzfHEBSUhJff/01J06c4OuvvyYpKQmFQkHz5s2ZOXOmtLc9a9Ys1q5di76+PoaGhixcuJDKlStz69YtunfvLrUfHx/P27dvefPmjdb4aGzCd+7cKTkn8vPzY+TIke8VcP7p3HiVKjlvKug+VLDMq1SakZFBQEDAn24lomHLli34+vpKbrg/JZk5goxstaJvfh/Pd30M+Pj4oGNhw8YVyyhsXYysjAyKObnSZtwcjAsXYWn/VqTHPsPKvAhPnjyhevXq7N27F6VSSXR0NL179yYiIgIDAwPJxbNG/yA3ud+Z+NjnbBjdi8/XHEBXqWTFID94+wpjPbVy8MKFCyU/BY0aNeL58+eSX5Y6depIVkW5895X7908X19f1q1bR5kyZT75+Mv8Bv7KZQuZfza5lyUfPQ4XhQsXFtduBGu5cd27d68wNTWVXJq+qwfx4sUL8dlnn4nPPvtMq11vb2+xfft2Ka1r167Cx8dHDB8+XAih1tM4e/as2Ldvn/Dy8voofYrJF56K0vZlRFJSkhBCvVwcFhYmhFAvodeoUUPax75x44YoXbq05JJ5/fr1olKlSvmOw+DBg8WQIUO00sLDw0W1atVE1apVtXQBbty4UeBy7b8JzXKzxm3xzKBY8cPes8LVw1NrC8PLy0vMnTv3r+7uH8bTxAwR+M44BOaz7J77XdIwceJE0XfQULEjLEFMv/pcuNVtLmp2+0LsCEsQVWvWkp6r8PBwYWVlJbZs2SKEEOL58+fStpEQQnz55ZeiZ8+e+fYt9/tRxa+3lkvp706HihlBsep7uWOH8PT0lOrm3hr5/PPPhbu7e75576v3bt7OnTtF9+7dCxxLmT8X2VpB5nfxPEUdlS0w3oTCpcry3dpdZOYgObmpX78+iYmJeWbVGqytrVm7di3Hjh3jzp07Unrv3r1ZtWoVAAkJCVy6dIkmTZpI+RYWFtSsWVOyN383JG9+3Dm2lzKqylKdChUq4ODgAKg11FUqleQd8H1henOTlpbGxo0btQL15LYJf1c7+98Upvd92Jro0cahMKO8ijLU3YJRXkUZ1aImd26G5OvH4VPSrFkzfvzxxzzpXl5e7Nixg7CwMNq3b0+ZMmXw9vamcuXKWr40AHr27EnhwoWl+6/B3t4ea2trMjN/iTp48uRJFAoFI0aMANTeSOvUqYNJYTOqeFeQAhPBLx4ONzxK4MYrbRPHzZs3M3PmTK00Y10F/m18GV+lBHEPggnZvYGJrWty9eJ5OnfuTJEiRbC3t6du3bo8efKEw4cP07hxY4YMGYJKpaJEiRJs376diIgI0tLS8Pb2JiFBve2T+53JTE/j5pFduNdvIZ3byNRM8knxbuTQ3CaGVapU0Qr9njvvffXezWvevDkHDx6U+ifz1yILB/9AsrKymDRpkhQ1TaVSMWDAAC5dukTp0qW1Iuv5+fkxceJEgPf+KPr7+2NlZYVKpZK8Er548UJqZ/r06ZQvXx6lUsmuXbsAyMgRHHiaRGhCBjGP7hIb8QiXOk3IEYINjxK48PQ1rq6u1K5dGysrK3r37s3XX3/NyZMnqVGjBlevXgXU9stly5ZlwIABODo68uzZM1JSUoiIiCA6OpqhQ4eSkJDAtGnTuHHjhtZYrFixgvv37zO4SXUWdm3AwwsnpLwLm1dq2deHXT+PWTlVvt4fnz9/zvbt2yWHOe8L05ubHTt24ODgoOUqOrdNeH7808P0/hr0lAqM9ZR/6j503759Wb16tVbatWvXiImJoVKlStSsWZPGjRsTHh7O9evXOXz4sGQWCfD27Vv27t2Ll5cX27Zty9N+6dKltcxHAwIC8PHxkY4LFy7M0G/9aT9VHUL6Qx4OQW2GN3fuXH7++WdUKhU7d+4E1L4VKleujImJCW5urowcOZKrV6/i7u7O9OnTAXX8hpCQEFq0aEHjxo21BK8KFSqgVCpp1aoVhoaGdO/enR9++CGPL4WoOzewKFEafSPtyJ2bJwymd3UXJkyYkMfDY48ePShVqtQny9PT08PDwyNPmHCZvwZZOPgH0rdvX65du8bFixe5ffs2N27coGHDhlhbW9OlSxfJ9fLGjRsJDQ1l/PjxPH/+/IM/il27diU4OJg7d+5gaGgoeX0DaNCgAQcPHqRWrVqAWvEsNUuw6ev+zO9Uh53TvqTdxAXo6OqRnpLEwk51qO/mQFRUlDQbatOmDdOmTaNu3bp88803WmGdY2Nj0dPTIzQ0FBsbG2bMmEG7du1Ys2YNQUFBrFu3Lt94E56enjiWK8fwLadoN3E+P3/dj4xU9WyvcrseXNv9M2mJasc2CS+iMSlqlcf749u3b/nss8/46quvpB/594XpzY3GPa+G27dvExgYqGUT/i6yi9c/lpYtWxIZGcnNmzeltFWrVtGjRw+WL1+Or68v/fv3l/LMzc35/PPPpeNNmzbRoEEDRo0ala/PkI9Z1VI4VsTAyPi9/cztKTIlJYWGDRty8+ZNyXXxy5cvuXjxIufPnycpKQlXV1e+/vprDAwMKFKkCHPnziUxMZHSpUvTtGlTXFxctNp/9uwZhw8fpnz58pIDqU6dOrFixQrSs3K0fFIkvIzBJJ8Q1h2m/MTXB0OY4D85T5yRdevWERkZydSpUz9Znvxu/H2QhYN/GKGhoWzbto3Vq1djbm4O/N/hiJ8fDg4OTJ48mZCQEBYtWsTo0aNZu3Ytenp6/PTTTx/8UdSgVCqlZUoNlStXlpbgQf2jpgA6z1zBsM2n+GLNATwaqGMgGBQyYdjmUxiZmdOkWz86depEWloaLVu2lJYfc/vxj4uL4+XLl1J0Ol1dXXx8fChcuDALFy7EwsKCpk2b5qtxXaVKFXSUShSAjaMrCEFy3Gt1O3r6OFWtQ/ChQAD0jAqRlZ6u5f0xMTGRJk2a0KpVK0aNGiWlBwYG4uHhISmnaaIX5nZmEx4ezqVLlyR3rgBnz54lIiICJycn7O3tuXTpEgMGDGDJkiVSmf+yl8c/Az09Pbp37y59wNPS0ti0aRN9+/b9KHfSGpfkLVq04NGjRzx48EArv0aNGtKq1qZNm/Dz89NaVtfMyj+k6Z3bU2RaWpqW8JuZmcnevXvp3LkzBw4cwNTUlPnz52s9NxMmTMDU1JTr16+zatWqPNFe27dvj6WlJbt27ZKUbIsVK4aRkRGP7t/VcoGsb2hEVnp6vv1UAL179+LkyZO8fv06T37Pnj0/WZ78bvx9kIWDfxhBQUE4OTlhaWmZb76+vj7Lly9n2LBhfPHFF1KwlV/jYz89PZ19+/blO1MGyPqIH7/4589IT06kxtDJFLW01Po4wi9+/OPi4ujTpw9KpVKK6gfqENdv375lxowZWhEY80Njrhi052csStpRpPgvkd5Ke/oQduWMuk1HV3Keh0tL3ElJSTRp0oQmTZrkmek7ODhIMzYgT5heUM9G27Rpo7WP+sUXXxATEyN5rKxatSrLly/X0sCXvTz+8fTt25eNGzeSkZHBjh07cHFxyTOzzo9bt24RExNDo0aN0NPTo1u3bpKQkZvu3buzZs0aVq1aJZkxasjIFh8UDDRoPEVmZWVpuWWeNGkSLi4ukpvj9+Hp6cmUKVP49ttvJQuhoUOHEhISwrJly7SeWVALCC+in2l5TC3m5Ersk1/ccKcmJvA29jlK1GbO+/fspmjRolhYWBAfH090dLRUdteuXb87T4P8bvx9kEM2/wvZuXMntra2WtHpPoaNGzdy6tQpwsLC8PDwoEOHDvmWy8r58I9fwotodZQ2hYJps2bTq2tnaWXgyJEjHDp0iFKlStGgQQPatGnD0aNH822noMhtKSkplCtXjvT0dBISEuhfuSzJaWkMXn9Ua4XBpKg1CS9iAHBv8BknZ/2yOrBgwQKuXLlCcnIyO3bsANQ6GuPGjaNNmzZcvXoVHx8fDAwMMDY25ueff5bq5uTksGbNGtatW/eBkdAmd5hemT8OV1dXHB0d2bt3L6tWrZK2fjTupAtSggwICCAxMVFaJcvMzCQnJ4dp06ZJgZ5AvW9esWJFypUrh5OTk1Yb+joKPlbDQqEpr1CQnmvmfvr0aW7evMmlS5fYvn07b9++xd7enqtXr+ZrkvjFF1/w448/smPHDooVK8aPP/6Irq4uEydOZOLEiZQpU0bSY9DMzt2sjXiYoF4Jsyhph4mFFS/C7mNT1pm0xLf8PLYvmelpWBjqUsLGmn379qFQKEhISMDPz4/U1FSUSiVWVla/Ow/UipzZ2dmycPA3QRYO/mFUrFiRR48e8fR5LMWtLfMoep0/f56tW7dKeggbN26ka9euH/xRBLXOwfz583nz5g0NGzZk4sSJ+c7adZXqH7+x+4Py5JmXKM3EM2HEPLxNVkY6CqB+3To8f/4cACMjI0qWLMnx48e1fOFv27aNJ0+eULx4cSIiIujQoYNWPiAFzwG1L37N3uTp06fp3r07i7fvI9ysrJZ9fVZGOnr/95Xfs14lHq214erVq1SqVIlx48Yxbty4fMdCoVAwY8YMrXCxuVEqlURGRuY/kLk4deqU1nHuML0yfyx9+/Zl+vTpUjRFgEGDBqFSqVi9erUkeMbHx7NlyxZ69+7Nhg0buHTpkhQECdRbV/v375ccGQGUKFGCGTNmaJXToIlj8vgD/VOiXvHSUyoYM2aMVmyJ3Ep5ERERWpY0oH6uIiIi+Oqrr9Tn1NPj4cOHUn63bt2ws7PLE20xOztbEv4t/h/GWuOTok7vYVzauopW33xP0RKlGLz+SL4+Kezs7Lhy5Uq+1/Rb8wCWLl3KV1999d4Q5DJ/HvK2wj+IyKRMbiqtca7bgqadezLt3GN2PH5LZGIGgYGB3Llzh169erFs2TIsLS1Zs2YNo0eP5vnz5wwaNIjTp09raXHHx8ezbNmyPOexsLBg5cqV/PTTT8TExOTJ1/2IIE6Wdo4kvYnFziBbEmC2bt3K+PHjOXbsWJ4Pv5+fH0uXLgXUe/mnTp2SHAe9jzNnztC9e3d2795NxzpV6OZkhpOZvjRziw1/iIu7J92czKhgacTChQu1rDD+bDRhemX+eDp27MiDBw/w8/OThLHixYtz7tw59u3bR5kyZfD09KR+/fro6emxa9cu7Ozs8nzwu3btWqBiYn5bdSkpKQz2dWXjV315+fghM5p4cmjRlDzlcoBK1uoPb/v27Tl8+PBHX5unpyfVqlXj7du32NraajnlSkhIYMeOHXm2OwDOnTtHpUqVpKX8CpZG0jvj2bAVVmXKIXJycDLTl96ZP4sSJUrk22eZvwbZQ2I+7Nixg2nTppGdnU1aWholSpTg2LFj1KtXjydPnmBmZkZqaip+fn6SZK5QKIiLi9Paf9a4J1WpVPTq1QuVSiXZQs+YMYMNGzZw5MgRoqOjGT58OMHBwTRq1Eia5eQmtyezzMxMTqycy8UtK9AzLIRBIRPcXJ25d/0Kr169okWLFlIbkydP5tixY2RlZXHjxg3Mzc0xMDDA1NQUPT09mjVrxvHjx7l69SqlS5cmLCxMOmfv3r25d+8esbGxxMXFkZmZSUZGBqampmTnCPSLWKKjp0d2ZiaudZvRaPC3KBQK7p05wr3Th0hJeMOYL/rTs716xqWnp0exYsW09laPHz9O0aJFSU5Opk+fPly7dg0dHR2mTp0qbWusWbOG8ePHExcXh56eHiYmJlLEOCcnJ96+fUvx4sUBeP36NcbGxhgYGiIEPA4LpXjx4qxatQpfX99P9ITIyHyYX+spsnnz5vj7+1OpUqU/pD8vX76kfPnyWFhYYGpqKqU3bNiQ2bNnf9CLo8x/C3lb4R1iYmIYMGAA169fx87ODlArAWqWuubNm0fr1q2Ji4ujQoUKVKlSRYpD/rGMGTOGM2fOcObMGYoWLYoQgvnz53Pjxo08GsegXjE4EqU2z8sBdPT0qNyuB7eP7WHE9nPq/bwX0YwyTCL6wS2tNr777jv69OlDdHS01H5u4SMqKorPPvss33P37t2bL774gps3b6Krq0uNGjWYNGkSzZs3JzExkYepSo4+SyUnM4MlfVpg66rCrV5z3Go14tjSWYz4aizb1qyQhIPcjmPexdjYmC1btuSb16tXL3r16pVv3qNHjwps8+7duwwcOFC2m5b5S6hgaYSVoW6eOCZOueKY5GbhwoV/qHOswoULM3369ALdU+spZaFA5hdk4eAdXrx4gY6OjpYGbcWKFfOUMzc3p3Llyjx48OCjhYPs7Gz69etHREQEx48fl5Y6bW1tsbW15e7du/nW03gyyz37uLb7Z9zqt5CEFnObEmSZ6WMQ8TBP/fe1/768LVu20L17d8mjYJ8+fdi0aRPNmzfH1NQUb1OwKaTP6bAXZGVkgEIh/fj17NyRV/dDaNu2LYmJiVozlT+LyMjIfLdNZGT+LGxN9LA10SMzR7B8xQqWL1mcR1lx0aJF+Pr6UrZsWcqWLfuH9cXQ0PAvi1sh889DFg7ewdPTk5o1a2JnZ0ft2rWpXr06Xbp0oWTJklrloqKiOHfunNbL5uvrq2XvnNtsB9RbCe7u7hw+fDiPW92CKMhmOvzaeWp0/cVHgcZm2jIf73+/ladPn1KzZk3p2N7ens2bN0vHFy5coH79+qSnp1O0aFGC1/zAzXVzcXdzY+DAgYwaNeqDZoh/JI0bN/7Lzi0jkxs9pYLBAwcweOCAv7or/0jkLY8/H1k4eAelUklgYCD379/n9OnTHDx4kGnTpnHt2jUARo4cib+/P3p6ekyYMIG6detKdc+ePZtH5yA3derU4cyZM5w7d4769et/VH8KsplOeBmdx6OZALL+RBWS6tWrk5qaSmxsLO3atWPq1KmSB8WHDx/Kns5kZGR+F3II9r8O2VqhAJydnRk4cCC7du2iatWqki/1efPmERwczNWrV3/1El3NmjXZvn07nTt3LtCu/10KspnWMzQiKz1NK00B6H5CM6DSpUtreUmMiIjIY2UAYGVlRbNmzbT80MuezmRk/l3Y29sTHBxMr169mD9/fp78q1evUr16dQoVKpSvpdHUqVOlrZOCTIhzExSbStdBI9i+dQsCCDm8kwWd6jCoURV8VJ6MmvxLkKqcnBy+/PJL3N3dcXZ2pm/fvlreTGfNmoWrqysqlYqqVatKJpXJyclUqVIFLy8vvLy8aNKkiWQy+m6gqv8asnDwDs+ePeP8+fPScVxcHOHh4Z9sL7BWrVrs2LGDrl27fpTpkl4BZoPFnFx5lcujmcaTmc4nXHLz8/Nj/fr1JCcnk56ezqpVq+jUqRMA9+/fJydHrQWRmJjI/v37JW+MIHs6k5H5r1G8eHHmz5/PvHnz8uSdOXOGTZs2cfPmTe7evcvhw4fZv39/gW1FJmWyLSiUB+eO4dGoNQBmNiXo/eMWRmw7y+er9rN2xTK2HTwGqJ1XBQUFERQUxL1791AqlSxYsACA4OBgFi9ezJUrVwgODmbIkCFS/BkjIyOOHTtGSEgIISEhNG7cWIpDkTtQ1X8RWTh4h6ysLCZPnky5cuVQqVT4+vrSs2dPLQcov5eaNWuyc+dOunfvzsGDB3nw4AG2traMGjWKw4cPY2try+LFi6XylayN8kR286jfkocXT0rHLyJCGeTrmm8b72v/fXl16tShY8eOeHh44OLiQsOGDaWohVu2bMHd3R0vLy+qVatG/fr16devn9SfQ4cO0b59+082ZjIyMn9vbG1tqVy5cr76VLmVmw0MDCTl5oK4+jKV6+8oXdurqmBqaQOAoWlhrO2dOHNLba0UEhJCgwYN0NfXR6FQ0LRpUyni4/vCryuVSklZWgjB27dvtZwwaQJV/Rct/mWdg3ews7MrcEb/rre73OT38OT2aLZmzRqtvBo1avDy5Uvp+H3786Xe8WSWA5T3bcjx5bN5+yKawjYl6ObrxQ/P8m+jfPnyBbb/vjxQm0J+9913edI1blnz49WrV1y/fl22FJCRkQE+rNycG40S9uN3lK5z8+LxA57cuobpuDlk5gi8vb1ZtmwZQ4YMwcjIiK1bt0q/v7nDr1tYWGBgYMCZM2e02mvQoAG3bt3CyspK6/dfE6jqzp07uLu7/85R+Gchrxz8Q8jtyUyBWuJtM+4HTN7G/OmezD5EWFgYS5cuzRPwRUZGRuZDaJSw81O6BnXclvUju9Pm29kUtilBRragV69eNGnShNq1a1O7dm3KlSsnxcL4mPDrx44dIyYmho4dOzJt2jStvP9qGGl55eBvzOTJk6WAQLnZvG07pewd0Peq97c066lSpcpf3QUZGZm/ER+r3Ay/KGHnp3T9NvY5AV+0o26/UXg0bKUVuMrf3x9/f38ANm/ejJubG5B/+PWhQ4eSkZGhNYFRKpX0798fJycnrW3d/6pytbxy8Dfmu+++Izg4OM+fs5MjxnrKv6VgICMjI/Mu71NufheNEnbxd5Su38Y+Z+XAttTqORTvzzpJSth6SgVpaWnExcUB6m3NmTNnSkGp3hd+/fnz51I9UOtG5Faszh2o6r+GvHIgIyMjI/Or8Pf3Z86cOdLxvHnzpCBWKSkppKamYmtry7fffsugQYO0lJtBHRRLo9ycH5WsjXCv35Kg/Vuo1EYdVOrY0lnEP3/GhU3LubBpOQCjR4yAL/qRkJBAnTp1UCqV5OTkMHz4cMlz7fvCrz99+pSBAweSnZ2NEIKyZcuyYcMGqR/vBqr6LyEHXpKRkZGR+dtx/WUyrerUoMfcdRS2KSGlFxS46o+gU6dO9O3bl4YNG/6h5/k7Im8ryMjIyMj87fC2Nmb5smWYvI2RHMFpPCT+GUrYaWlp1K5d+z8pGIC8ciAjIyMj8xdRkNJ1YGCgluM5ObbCn48sHMjIyMjIyMhoIW8ryMjIyMjIyGghCwd/EJk5guTMHDI/YQhlGRkZGRmZPwPZlPET82eFGJX34GRkZP5q5N+hfy//2pUDTXhRUEcNNDExoW/fvlplTp06hUqlko6Dg4MpVaoUW7ZsITo6msaNG1O+fHn09fUxNTXFzc0NR0dHWrVqxYULFwB1zAQzMzNUKhXl3T3x8XKnZyVHsnNyuL5nE+OqlKBDeUtKmepjV9aJa9euAfD48WMUCgVVqlTByckJDw8PunXrJrVnZWUlBRHRXAeohY9xAduxd/PCyd2TUuVcGTp7KQOHjWLz5s34+fkxbtw4qU8qlYq6detK9VNTU+nRowfu7u64u7vTsmVLYmNjpfyAgACcnJwoW7Ys/fv3JzMzUxorIyMjqU2VSkVqaioAN2/epGnTpp/s3snIyPy9iUzKZMfjt8wNec2i22+YG/KaHY/fEpWU+Vd3TeYT8a8VDnKzZcsWvL292bFjh+Ql613OnTtH8+bNWblyJR07dkRHR4cJEybw4MEDSpQoQdu2balUqRKhoaH07NmTZs2acfnyZQDq1q3L3nNX6b3+BGW8a9B0hD9KpXpobd0qMmbvNYoUL0Wracsp5qwOY7xq1SpKlSrF/fv3efDgAbdu3ZKcitStW5fAwEAeP36MnZ2d1Meg2FQ2PIxn3qj+tPdfxLDNp+i5YCNLxg1nx569lKvfknHjxrF9+3bq1q0reVQ8efKX6I3Lli0jJSWFW7ducfv2bWxsbJg9ezag9kE+YcIEzp49S2hoKC9evGD58uVS3fLly2t5atS4FPX09MTAwIATJ058qlsmIyPzDllZWUyaNAlnZ2fc3d1RqVQMGDCA+Ph4AE6ePIlCoZCiEWqIjIykZcuWeHh44OHhgUqlkt7V3JMbNzc3mjZtytOnTwEYN26cVF6lUkmBkoJiU9n4KIHQ/6+OAgggNCGD9Q/jqVC1huQq+dtvv8XZ2RkvLy98fHy0ghoNHjxYa7JhaGjIwoULAbh69SrVq1enUKFCtG7dWut6Nm/ejEqlkiY4uUMqyxOVT8d/QjgICAhg7Nix1KpViy1btuTJP3jwIJ06dWLbtm00btwYABsbG60oYu7u7lKUr7Zt2/L5559reQi7+jKV7PQ0bh7ZhXv9Xzx/GRexwOz/DjyUmnLZ2axatYo3b95QqlQp6eNdrFgxqV6tWrWksKKgltSPRKlDjqJQkJaYAEBaUiK6+vq41WvOkagULB3dSExMJDExMd+xUCgUpKSkkJmZSVZWFklJSdJ5tm/fTsuWLSlWrBgKhYLPP//8vWFVc9O5c2c5CqOMzB9I3759uXbtGhcvXuT27dvcuHGDhg0b8ubNG0D9O1e/fn0CAgK06n3xxRfUrVuXW7ducevWLY4dO4ajo6OUr5lI3Llzh3LlyjFy5EgAxowZw61btwgODmb//v0MGDCAkIgY6Xfo3TDyOcCto7vRLWaPTlH1b56vry83btwgJCSEgIAAOnToIIVO/umnn6SJxqFDh1AoFHTo0AGA4sWLM3/+fObNm5dnHEqVKsWhQ4e4ffs258+fZ8mSJVLEXHmi8un41wsHd+/eJTIyksaNG9O3b988L87jx4/p0KEDBw4coHr16vm2IYRgy5YttGrVSkqrUqUKd+7cAdQS+5Cm1Znn50tWWipXAtdJ5cKunWNhpzokxj5n5/QxPEzIYP/BQ1haWmJpaUmxYsXo0KEDvr6+HD9+HFCvYqhUKqpXr05KSgqgFiqUqD/uXWauYMOY3sxqVoFlfVtgUdIeO6/KkvBRtmxZLl26JLWxbds2qT8DBw7E1NQUa2trbGxsSEhIYMiQIQBEPHlCcdvSkhKlvb29NIsAdbTFihUrUqlSJa3AJADVqlWT+i8jI/NpCQ0NZdu2baxevRpzc3NA/Vvg5+eHg4MD8fHx7N+/nw0bNnD37l1CQ3+JSRAVFUXJkiWlY0tLywKDHjVu3JgHDx4AUKRIESk9KSkJIQRBL1Pe+9G4EriOCk3acfWlesuxadOm0gqjh4cHQgitbUwNa9eupXHjxtIEydbWlsqVK2NgYJCnbI0aNaRyZmZmODs7SxM3kCcqn4p/vXAQEBBAjx490NHRoVmzZoSHh3Pv3j0p38bGBk9PT5YsWUJ+Lh+EELx584bChQszfPhwrXQNtWrXYdjmUzQY9A0OlWpSs9svMcjL+tRk2OZTmFoVo9W3sxH/71PLli158uQJbdu2JTs7m6lTp9KxY0cqV67M06dPCQ4OJiAggDdv3nAjOIRHCRnkANlZWZxYOZdus1cz9sAN+i7dwfOwe+jo65MDPEzIoEJFbz7//HOpjVGjRnHp0iUAjhw5Qk5ODs+fPycmJoYiRYow4utx7Hj8lhuv0rj4IkXaP3ye8sv+YcWKFYmKiiIoKIidO3eydOlStm7dKuUXK1aM169fk5amHUVNRkbm9xMUFISTkxOWlpb55v/888/Sx7Vbt26sWrVKyhs7dix9+/alRo0ajB49mjNnzuTbRnZ2Ntu2bcPb21tKW7hwIeXLl6dixYosXrqMl3pmeVYMpPqZmTwJuUJJj4o8TMjIY6m1evVqHBwctLZKNaxatSqPTtjHcPfuXS5evEiDBg2kNHmi8mn4VwsHmZmZrF+/nrVr12Jvb4+joyMpKSlaqwfGxsYcOnSIW7duMXDgwDwCwrBhw8jKymLWrFmSHgGo98Tc3d0BtQSvAPQNjchKT39vn5LjXnH44AHp5Z01axZv376lQ4cOpKSk0LRpU1avXk1ERATu7u4IIRgz5ksWdqlP2NVzxDy8zdvY5+Tk5PBNRStiwx+hq6fPi0d3ATi69HtWrFjOxo0bcXFxYezYsdSpU4fz588Dap0DY2NjKlWqhKenJ2cvXmLFksUcPnaCIsVsiYuJkvYP1128S9Hi6i2HwoULc/bsWT7//HNsbW3p3LkzCxYswN3dHVdXV9q1a4dSqZRCoK5du1bar6xQoQIHDhyQxuDQoUP4+Pjg6elJ1apVCQkJkfL8/PwkZU8ZGZmPIyAggD59+gDQp08f1q5dS3Z2NqCeST99+pTRo0cD0KpVK0nPCNQrnyqVCm9vbxQKhdYe/rBhw3jw4AEXLlxg5owZJMW/KbAPyfGvUSh1MChkggAysn/5LT1+/DiTJk1iy5YtKBTaVg1nz54lMTGRZs2a/aprjoqKolWrVixdulRrC1aeqHwa/tXCwZkzZ3BwcODZs2dEREQQERHBpUuXWL9+vaSFD2BqasqhQ4e4d+8e/fr1IydHLRsPGzaM0NBQrK2t0dP7xQxx9+7dLFmyRHrZlAq1uWIJJ1dic4UYfRclEHkskNatWxMdHU3Dhg1ZsmQJVlZWGBsbU6hQIX788Ue+/fZb3r59i4mJCUqlkilTplKv70g2je1HYeviJL56wbkNSyhbuRYXtwSQk51NTnaWdJ6iFhYsXbpU2vbYs2cPFSpUAODly5ccOHCAAwcOcOTqTUpWqoODT01ePgnFvX4L7p0+ROKrF2QLwZXtaylVpyVRSZnExMTwzTff8M0335CYmMiGDRsIDw/n4sWL3L17lxIlSmBubo5SqeTNmzcMHTqUo0ePEhwczKJFi+jVqxcAcXFxdO3albVr13Lz5k1mz55N165dpb6PGzeOr7/++vfdeBmZfxkVK1bk0aNHvH79Ok9ecHAwN2/epH///tjb29OiRQtevXrFwYMHpTLm5ua0bduWH374gSVLlmgpLeZWXl61alW+qxNeXl7YlixJ+PXzBfZR37AQ2ZnpCCHUkyUdtRBw+vRpevfuzd69eylfvnyeegEBAfTs2RMdHZ2PHo/o6GgaNGjA+PHj8fPz08pLS0tDR0dHmqjI/Db+tcJBVlYW+/fv1/rwALi4uFCyZEn27t2rlW5iYsLBgwcJDQ2lb9++nD9/nkWLFhEREUFMTAxVq1bFzMwMR0dHAgICOHDgAFWqVAHUkveE1r6sG92TlIQ4Vg3uILUb/eA2M5p48vZlNAGDO/LznElSn5YuXcrs2bOJi4vj6dOnjB07losXL5KRkUHVqlV5+/YtOTk5+E/8jqML/EmOf42Oji7NR0/lwfljvI19zrP7Iaia+RF1NxglYKaTzcuXL/nmm2+oWLEi169fp1SpUtSrV4+kpCRu3bqFSqWiSZMm1PD2Ivn1S9pOmEuV9r2wsLWnwedjWdqnBXNaVcbYvCjV2vXk6stUZs2aRVhYGC1btqRq1aqULFmS5s2bY2pqKl2rxhIkJycHIYSkFBkfHy9J9mFhYRQtWhQ3NzdArbD09OlTgoKCAFCpVMTGxmpt/cjI/NdxdHSkXbt29O3bV7JOEEIQGBjIhAkTGD16NE+ePJEmQfPnz5dWSPft2yfpLgkhuHHjhlbcgoK4e/eu9P+wsDCCg29Q2dO9wI+GoWlhClsVJy4ynHJm+ugpFZw5c4bu3buze/duvLy88tR5+/Yt27dvl1Y9PoaYmBjq16/P2LFj6dmzZ578e/fu4e7urrXSK/Pr+VfGVoiJiaF8+fI8f/6cQoUK/WnnvfEqlTmrfib82nlafvO9lP6hEKP29vbs2rULlUrFrVu3qFGjBtevX6dSpUrSD8Hsn5YzfeoUxh64wcWtq4gIukjnmSvY98MEdPX1Cb10mu5z13Fl/tckvnnFlStXSE9Pp23btnTs2JEePXpw5coVGjZsSEJCApk5grkhr/mYm68AUvcuJuntW8lC4+TJk/Tt25cLFy5gbm6Ora0tr1694vXr11hYWLBx40Y+//xzLCwsSE1N5dixY3h6epKQkICDgwN79+6levXq7Nmzh1atWhEYGEjbtm0B9bJoxYoVJUVJGRkZ9Tbp1KlT2bx5M7q6uuTk5FCrVi1WrFhBSEgIHh4eUtnXr19TunRpHj9+zJw5c9i3bx+6uroIIShfvjwLFy6kZMmSrFmzhl27drFr164852vRogXh4eHo6emhq6vL2LFjqdq0NRsfJRTYx/1zv8OipB0/jR+FrYkeTk5OvH37luLFi0tl1q9fL/V1+XL1Fujp06e12nnw4AH169cnJSWF1NRUihYtyrfffsugQYPo378/P//8M05OTlL54cOH07t3bwAmTZqEjo4O48eP/03jLKPmXycczJ07l2XLljF69GgGDBjwp58/KimTSXMW4PBZDxRKJQqgnJk+ld7jIdHe3h4DAwOMjIwoVKgQo0aNwsfHh7Jly0ovUcmSJekx5jvCzcryY5f6NBo6nnLV6vI89B6rB3eg2w9r8TbXYeey+Vy8eBFbW1vCwsLw8PDgxIkTGBoacuXKFRo1akR8fDzJmTnMvfaMJb2akp2ZialVMfotDSzwuh4u/haXck6MGTNGSlu8eDGrVq0iMzOTChUqsHbtWhISEhBC0LBhQ9auXYuLiwt79+5lxIgR3Lt3D319fU6ePIm/vz9JSUlUq1aNkydPMmPGDFq2bAmobaNzcnKYOXPmp7sxMjIyn4Qbr1I5HJksTXo0KIE3MVHsG9+PW9ev5tEt+DPIyMjAx8eHEydOFKi8KfNx/OuEgz+aly9f0qhRozzpDRs21FLy+TVuRXOvHGiIiIhApVJJKwea0KaJySk8Dn2Ejq5a0DC2sCQl/jUrNmyhl19r/P39iY+PZ/78+bx584aGDRvSoEEDZs2aRVJSEpaWloSEhODgVE5aOXh87Tz75oxj2OZT+fZPAUSvnYpl0aJMmDAh3zKXLl3Cz8+PyMhItm/fzvLlyzly5IiUb2VlxYULF7SkfYD09HSKFSvG1atXJdvrUaNGYWZmxsSJE987bjIyMn8NUf93E/8wl5t4zSTo8uE9VKlSRUtJ8M/iwYMHhIWF/WrlRpm8yLEVfiXW1tZa7owLQk/5aX2Nf/fdd3z33XcMHToUY+O2TJk+QxI+Vi5byu6f19LLr7VWHQsLC1auXImvry8jRoygePHijBo1in79+rF582aczEwJTcggIzW5wPMqUStbWnt55TEPiomJoXjx4qSkpPDdd9/x1VdfAeDg4EBwcDDPnz+nWLFiXLx4kaysLEqVKqVVD2DKlCnUq1dPyynLvXv3GDhw4CcYNRkZmU9Ny5YtJf8nAhACLCzMGft/Z2627dr9Ief9mAlX+fLl81V6lPn1yBob/yDS0tLYuHEjXbt2RU+pwFhPiZ5S7VXsyJEjvHjxIk+dChUq4Ofnx/Tp0wGYNm0a7du3p0mTJnzVpBKL+zTnwuaVNB6a//5cDlDJ2ogWLVpw/vx5yTwKoFGjRri5ueHl5UXNmjUlHYGKFSsybtw46tWrh5eXF0OGDGHr1q0YGhoCakHH2dkZR0dHnjx5omVampyczK1bt7TslmVkZP4e2NvbM3nyZElxWAFkpKdRytZWUnrUlCtfvrzkGrlfv34A+Pv7Y2VlJaW/qzCeH5FJmVRv1prh6w6x6PYb/L79Hrvybrh5euHu7i65XNYQGBiIh4eH5F45t4MkUK/+2tjY5HHLfPr0aSpVqoSbmxuurq5cvHgRUCt0/hVb1H818rbCf5z37R++q0Q5ePBg6tSpk8d06FOydOlSoqKimDp16h92DhkZmd+GZgt0/vz5qFQqRowYQXp6OvXq1aNVq1b/Y++8w6K4ujj8LkiTZkFEREUUlL6ASuzYe2/YNdZoYq8xGjWWGBN7V+wasWDvPfZGtURBRcGCgEqTsrDz/bFhwgooJjEx+e77PDzJzm0zA+6cOfec35G9h3ltlQJa254FITA2Fb8j5zi6eAb9VwYAkJaUSGFTM9RAzSJZdK9blb179+Lh4UFQUBBdu3bl1KlTWFtbk5SUhK6urlZgepu27ShStCivXr5k3949gCY1skaNGhw+fBhHR0fS09NJTU2VVSK9vLw03ta3tkX/ywjPwf85HhZG9LA3x95cn2xHXXaZ6R725lrZFdOnTyf9PSJPfxYdHR0mTpz4UdcQCAR/HQYGBtSqVUsutvRXkV1P5uquDbg3ay8fN/zNMAA4HB5LesbvmjU//fQTo0aNwtpaU9vB1NRUNgyiklUM+X4JL02seGPrwf3EDLmS5LJly+jWrRuOjo7yNeWUj+7cuTNr1qz5S6/vU0cYBwJsTPRoZ2eG45MrbO3TkK19GzKtfR1a1qqKUqmUi1UVL16cHj16fNRzGThwIMbGxh91DYFA8NeRkJDAmTNn6PBWrEGXLl3k7YPdu3fLx5csWYKDgwOlSpXCwsJCqzIjaMrDKxQKxk2ehg7w4MZFjMyKMqeFpzxHyNEAZjSozOwmrqRnqfn8889p27Yt169f5/Hjx9StWxcPDw8mT55MVlYWgbGpLD4Tyv5NfpiXtObXc8cBOPnLBap5ebBw8WJWrlxJ6dKlcXNz46uvvpILRGXX1smpHAkwd+5cWSG2Xbt2cvA4aFRzc1a0PHfuHKDZGvby8iIhIf900E8FYRwIZFq3bEFoSDAhOcoyBwcH06VLl3/61AQCwSfG3LlzcXNzo2TJktjY2FCvXj2tdn9/f/k7pF27dgCy/Pr27dvx8PAgLS2NvXv3yv2ysbKyYv+GlSS9iich5imFixTVmvvXX45Tzr0aw7adpnBxSzZt/Zkvv/ySN2/eEBQUxJEjRzh//jwXL15k1oIlHI1KZte04TQbOY2L/n5U9K4DQEkHZ4ZuOk4ZZXWsy5TFw8ODXr168erVKzlbav78+VSsWFFWzgU4fvw469atkxVivby8mDRpktY5njt3Tr6u2rVrA2BoaEjPnj1zGRqfIsI4EAgEgv8wKrVEikqdqxDSn2Xs2LGEhoZy7949rl+/zooVK947JmdZektLS2xsbLh+/XqufiUsS+LRohOn1vyEnqERWTm2DuIe3+fW6UN0+HYhpRxcKOPixf79B2jYsCFubm506NABIyMjjI2Nad++PSfOXSQjOYln4bfZMqYvyS9jObZsNuGXz7BxRA909fQoYlUah+r1yczMpFChQnTt2pXLly9z69Yt9uzZk0uJMSQkhFq1askKsc2bN9eSpH4Xvr6+rF69Os9Cf58SwjgQCASC/yBRySoCHiQyLySexTdfytVWo5NV7x/8AZQtW5bFixczffp0UlNT39k3Ojpa/v/ExETCw8P55ptvUCqVWm/eCgXU7zeSkCO7sShrx6unv5eOv/PLUYqXKU9h86Ikv4rjwbVzKN3dAOjWrZtceTYzM5MjR49hbOuIgakZU07fw8mnKU2/mkzzEVOx/8yH/isDePX0MfcunWb3qgUYm5gwZMgQDh8+jIuLCwMGDGDlypU8ePBAq/aDl5cXJ06c4Pnz50iSxJYtW0hKSuLly98LUzVo0AB3d3dGjRolb1GAxkAyMjKSa998qvzfGwcfy6oWCASCnGRmZjJt2jQqV66Mi4sLSqWSgQMHEhwcjK6uLkqlEnd3d9zd3Tl48KA8bv369Zibm6NUKnF2dqZZs2ayzkB+3Hjxhjq1a3Ptzn0k4OjiGfzUvjpfNq3BZ9WqsnT7Prnv0qVL5f3xt1MDY2NjadWqFW5ubjg6OhIXF5er2mFqaioTJkwgKSmJZcuWARqlwqFDh+Y6r0mTJvH06VO6dOnC2bNn6dWrF3fu3CE4OJiZM2fK/RSAe9mS1Oo2EEmt5lHwVbnt7vmTxD0KZ5GvD2sHd6RBu85MHD+OSpUqcezYMWxsbHB2dkapVFKyVClqdPs9DTEh5immxUtonVNR67KM2XuVhoPGc+zoUSpUqEBcXBwmJia0b98eR0dHzp49q1XIqV69eowZM4aWLVvy2WefUaKEZs5ChTTSQY8ePeLGjRtcvHiR2NhYLWVZ0BgIOQ2lT5H/21TGqN8UvsJzKHzZm+tT7R0yxwKBQPBH6d27Ny9fvmTjxo0ULVoUSZLYuXMnXl5eeHp6ygFtBw4coFu3brx69QpdXd1c9Q+GDx9OdHQ0u3blLXcelaxi/NINhF86TYdvFwJw98IJ7LxqomdoxLN7N1nZvzWhEY9xKFmEhIQEzM3NAc3bvIuLi5waOGLECHR0dJg3bx5ZWVm0aNGC1q1bM2TIEHm9YcOGkZqayrVr17TiBtq2bcuwYcOoX7++1vnllQ6ZkzNnzjBixAj2n7/GutBn/NjWGx2FDgodBeMPBRP3+D6LfOsz8UgIRmZF6GFvjo2JXp51It6uIbNpdG+c67XAs2Vn3kYBlL5zHP+ft7J//365KJwkSTx79oysrCzKli3LtWvXZGMgm5wKsW9z6dIlBg4cSFhYmHzM09OT+fPnU7du3Tx/h58Cn4TnIDui08nJSbaglUolXbp0ITIyEoVCQb9+/eT+ycnJWrrdPj4+lC9fXh73PunMwNhUug8Zwc7t/khAyNHdLPT1YUhjb6oo3Rg1/XdN/0uXLsnzOjs7M2jQIDmd79SpU1SrVg0nJyecnZ0ZN26cVtBKftGs/6aIVYFA8OeJiIhgx44drFu3jqJFNcF1CoWCTp065aoe2KBBg1wu6pw0adKEu3fv5rvWtRepXN21Efemv2cPVKrZED1DTVpyyYpOIEmcvqt5kGUbBqARIctZzl6hUJCUlIRarSYjI4M3b95oySKfOHGCJ0+e5Clm1LVrV1auXJnveb6PMiZ6tHIoQYMBY8jKypQF2CzKVsDZpym7po2ghplKfpnL6brPRk9Hgb25vvygs6roRNyjCLk97vEDslQqdIDyRrB/7x7c3DRbFOfOnePRo0fs2LGDbdu2YWZmRmRkpGwYPHv2DCCXQuyrV69kQSi1Wo2/vz8eHh7ymllZWXLdm0+ZT8I4yI7oPHToEKampvLn7BS6woULc/jwYa0Som8zf/58rXnyIypZxY7ACO6eP4Fr47YAmJe0pu8Sf0bsOMfgtQfZsHolOw6fADR1zLMt4rCwMF68eCG7zooWLcq2bdu4ffu27ELauHEj8O5o1n9TxKpAIPjzBAYGYm9vX6BiQDt37qR+/fq53k5B82DZsWMHXl5eeY5VqSV+jUvhUchVyrh65tnnxr6tFCtdjlcmVvJ26s6dO3F2dsbW1pYxY8bID7PJkycTERGBlZUVlpaWODo6ygXSXr9+zbhx41i+fHme61SvXj2X5Hp+DB48WEtN8e7duyiVSiobw/yxQzAzM5PrySiAifNX0shbyYDmPjg7O1OrVi1OnDjB+PHjc81d1dJI1kVwbdiKe5dOy20Prp1ncbf6zO/iw+R2dShZsmSu+jHe3t553u/8FGJ//fVXPvvsM9zd3XF1dSU+Pl5L9On8+fNUrVqVYsWKFeje/FP8K2or6OnpMXHiRCZOnMjevXv/1FzXXqRyY+9WnBu0lL0Ptkpvud3Q1AxLW3t+CQunU7OGWspaGRkZpKamyuNyWoOGhoa4ubtz7/5DVGopz2hWHx8fli5dCmgiVj08PJg2bdo/Ur1MIBB8OiQlJaFUKnn58iVxcXGcOnVKq/306dOyDoCnp2e+LxYZWRLJr+NR6OhiUNgkV3vElV84uepH+i3bCQoFGVkSejoKOnbsSMeOHYmMjKRdu3a0bNmSSpUqsW3bNpycnDhx4gRv3ryhdevWrFmzhv79+/Pll1/y9ddfY2lpmeeLm5WVFfHx8aSlpcnS6YAsZ7x+/Xr52LsyHWyN4MmD8Fy1FTrPnsH82e9XUi1jokeTMsYcjUrB2t4Jk2IWRN0KooyzB5916EW1Dr20lGDzPAdbWy0dA0BrmyAn1atXJzQ0NN+5li9fnqcR86nxSXgOCsLgwYO5efMmFy5cyLN95MiRsuWZ/QB+G5VaIjwhgwfXL1DGJW/LO+bBXR6FXcfUraZsVUdGRuLu7o6FhQXm5uZa+22g8Ub4XQlnk/8OEivXZl5IPCmlKnP0eP7RrP+WiFWBQPDn8fT0JDw8nPj4+Dzbsz2mjx49YsKECfj6+moF/tWrV0/2jK5duzZfD4S+rgIDw8JkqdJzpco9uHGBndOG0XvBZkrYVkTxW/+c2Nra4u3tzYEDBwBNWfbu3bujq6uLqakpHTt25PRvBZbOnz/PmDFjsLW1xdfXl9u3b2sVPUpLS0NXV1crkO/PkLOezIeSUwm29dhZJMfH5qsE+zFJS0ujbt26NGrU6G9Z78/wrzEO9PT0+O677xg/fjzVq1cHkGMUsvNkK1WqxJ49e3KJUWRT0a48P7b7jMjgK+z9fhxn1i3Uaj+6ZBaLu9ZDz8CQvT9M5EX8K0DzDyYkJITnz5+Tnp5OQECAPGbb6SvUb9SYqZ93pk7vrzi7biEzG7swtUcrnNv2pn7T5lrRrHXq1MHBwYH69etTrFgxOWK1Y8eOWFtbo1Aoclmo+bWlpKTg7e0tRzg3bdpUtspFXINA8OlQsWJFOnToQL9+/eR/w5IksWvXLq04JYVCweTJk7GwsMjXXf8u9HQUuNpYYFaiFPFRD+XjD29cZPvkofSat5FSDi7ooCmxrKej0Hrrj42N5dSpU/K+u52dHUeOHAFApVJx9OhRXFxcAM1LU/ZPtochZyzEnTt3cHFxyRVT8bFZs2aNlupi9s/DoMu0szNjZssqLBviyyj34rSzM/tbA9ANDQ354osv/rb1/hTSJ8TDhw8lc3PzfI+p1WpJqVRKmzdvlgC5rW7dutLu3bvznSObcuXKScN+PiWVquQidf9xnWRgYioN2XhUmh0YK/nOWinp6ulJbb/+UZodGCs1GjJBGvzFF7nm+Pnnn6WWLVtKkiRJj5MypIredaWSFSpLjYZMkGYHxkr9lu+UJp24LQHSlLMR0uzAWCkqKUO6cOGCpKurK506dUqSJEmaO3euVKRIEenMmTOSJEnS8ePHpZiYGAmQXr16pbVmfm1ZWVlSYmKi/HnevHlS69at5c/z58+XJk+e/L7bLhAI/gYyMjKkKVOmSA4ODpKTk5NUuXJlaeDAgVJQUFCu76wzZ85IJUuWlFJSUqR169ZJbdq0KfA6j5MypFo9vpBaj/9emh0YK80OjJWKlykvmRQrIZVycJZ/jl2+IUmSJA0cOFBydHSU3N3dJTc3N2np0qXyXA8ePJAaN24subi4SI6OjtLnn38upaam5lrz9OnTkru7u9axqVOnSt99912Bz1vwafFJpTJGRkaiVCq13o7fPnb06FEGDx5MZGQkDx8+lK3CESNG0LZt2zznyMbW1pavlmxm68rF2Hp8xtXdm6nTcwjllN4s8q1HifL2DFqzDx1AJ+o203u0JDAwkHLlyqGnp0dGRgY9e/akYsWKzJw5k4XHrjG6ZS3q9RtJg4FjtNaa6FmCkQEXsbK1p6x+Jgv6teXhw4dyWeXXr19TtGhRnjx5IhcJAc2bw6tXr7SKfhSkTZIkpk+fTlBQkJzK8/z5czw8PHj69KmIaxAI/o84FHyPQT18+XLjUaQc//bzqrb6McjIyKBKlSqcOnWqQEGYgk+Pf0VAYk6aNGmCnZ1drhrdBcW5mAEuDVpzabsfb16/pHyVmhxbMpP0lCSiwq4zv2MtdAsVwt5GU+5z//79+Pn5oaurS2ZmJg0aNGDy5Mmo1BJrfviOrEwVt04d4NYpzR6da8PW1Os/CoAto/uAQkGWKoP61atiZmYmn0dISAh6enq5BEX+CA0bNiQsLIwSJUpw9OhR+XjOuIZsV6BAIPjv01zpwOSJ41GkxvGycAktLZeqf4OWy8OHD/n++++FYfAv5pPyHHwoBfE05MTW1hYDAwPS1fAo4h4NB42lwaBxcvuV7Wu5tncrRY306N6pAxMnTiQhIUHroZ5NikpNh1FTSIh5SpuJP+Rqn+hZgilnIzAy1eQQl7l3mo1r18gPb19fX44cOUJgYCB2dnbyuD/qOVCr1cycOZNnz57JqZYANWrUYMqUKTRt2jTXGIFA8O+ldevWuZQSixYtKgcMZvN2lL9AUBD+dZ6DP4u/vz9KpZKZ8xczdfwYXOq3pKS9Ewqg14DBLJ40EhsTPS5fvoyNjU2ehgFoonz1DI3IzEh/75oKwM62nFzvPC0tDW9vb3bv3q21pfBn0NHRYcCAAdjb22sZB2lpaRgZ/T2RuAKB4O9j37597++EJkhRGAWCD+U/axxMnz5dK6sA4OnTp0RFRWmKfIz8ivioh4Rv/okZu3ajr6sgLuY5pUzMcile5YWejoIqSnfWn3j3P1AdNK48b9sqqFQqTp8+Tb169cjKyqJVq1Za+b8fyvPnzzEwMJAV1/z9/eUoY/j3KHEJBAKB4NPiP2kcJCYmsmrVKvlzmTJluHTpEra2tpQpU0Y+PnnyZCpWrMivoUF4eXnRuHFjWSa0Z8+esuJVfvRsXp8FY4fwJuEVhc01D+j1w7ry7J5Gu2BBx1oUL2vHL2fOoKOjw+bNmxk0aBBpaWlYW1trlfhs0aIFISEhADg7O2Nvb8+ZM2fe2fb48WMGDRpEVlYWkiRRoUIFNm/eLM/5b1HiEggEAsGnxb865uBTYMTUWdx7nYFP7y9R5zj+d0UFvwtfX1/69ev3rxDcEAgEAsGnw79GBOlT5Yevx1DL1gJ7c32yd/X+CeWtt/k3KXEJBALBp4pKLZGiUsuKuf8vCM/BewgODqZPnz65jvfu3ZuRI0dqHRNRwQKBQPDfICpZxbUXqYQnZGilglb7G1JBPwWE5+A9KJVKWdM858/bhgH8Oe1vgUAg+H8nKSkJExMT+vXrJx87c+YMRkZGeHh44OzsjLOzM6NGjeLVq1daY5cuXYqLiwuOjo54enrStWtXHj9+jLW1NTdv3pT7PXjwgFKlSvHw4UOGDh2qJbFsaGjIokWLCIxNZUt4AhG/GQYAEhCRkMHm8AR6DR3Btm3bAJg5c6bWHGZmZowapdG6uXTpknzc2dmZQYMGkZ6ernVdOcempqYCmtT0MWPG4OLiQuXKlenXrx8ZGRkAxMTEUK1aNTIzMz/Gr0BGeA4EAoFA8EmwZs0aNm3aRGhoKFFRUZiYmHDmzBlGjBhBcHAwoDEgRo0axY0bN7h27Rq6urp8++23HDt2jB07dmBjYwPAyZMnMTU1JTIykjlz5nDlyhV0dXXx8fGhR48eDBgwQGvt58+fU758ec7fvMfxxPy3gxNePGPtFx25HhJGGVPtolLp6elYW1tz7NgxvLy8ePPmDXp6eujp6aFWq+nQoQN16tRh5MiRua4rJ6tXr+bnn3/myJEj6OnpMXDgQBwcHBg7diwAI0aMwM3Njc8///xP3O13IzwHAoFAIPgk8PPzY/z48dSpUwd/f/88+5iamrJs2TLi4uI4cuQIKSkp/PDDD/j5+cmGAUCDBg2oVq0anTt3xsHBgVmzZrFo0SKMjY1zGQYAGzZsoEmTJjxSmL/zwXh971ZcGrTkemxudds9e/ZQpkwZvLw0VX8LFy6Mnp5mCyIjI4PU1NQCSdmHhITQsGFD9PX1USgUNGvWTCu7rWvXrqxcufK98/wZhHEgEAgEgn+c27dvExUVRZMmTejXrx9+fn759tXT08PDw4Nbt25x69Yt9PX1cXJyyrf/0qVLWbt2LT/++GO+865du5befT8nPCFDK/PsbR5ev4CNixf3EjJyBSn6+flpbYmARrXX3d0dCwsLzM3NGTJkiNx2//59PD09qVq1qpZ4nZeXF/v27SMxMRGVSsX27du1SgZ4eXkRGhpKYmLiO870zyGMA4FAIBD84/j5+dGrVy90dXVp3rw5Dx8+5M6dO/n2/5Ad8WLFitGzZ0/atm1LqVKlcrWfO3eOpKQkGjRpxvtmTXjxFJPimnoVGVm/93706BHnz5+ne/fuWv1tbW0JCQnh+fPnpKeny+J8np6eREdHExgYyO7du1mxYgXbt28HoE+fPjRt2pS6detSt25dHBwcKFTod1miQoUKUbRoUZ4+fVrge/ChCONAIBAIBP8oKpWKTZs2sWHDBmxtbalYsSJv3rzJ9y1fpVIRHByMi4sLTk5OZGRkcPv27Xeuoauri66ubp5tfn5+9O7dGyP9QrzP6a9naERmehoKNDL62axbt442bdrkKzpnYmKCr68vW7ZsAcDMzAxzc03tHRsbG7p27cq5c+cATR2dqVOnEhQUxMWLF3FycsLZ2Vlrvo8tjS+MA4FAIBD8o+zbtw87OzuePHlCZGQkkZGRXL58mU2bNqFSqbT6Jicn89VXX2FhYUGTJk0wMTFhzJgxDBgwgCdPnsj9Tp8+zdWrV9+7dmJiIjt37uTzzz9HT0eBvbn+Ox+MVvZOxD+KwMFcX85MU6vVrFu3LteWQkREhHz+GRkZ7N69W5a4f/bsGWq1ZgMjKSmJAwcO4OHhAWge/NnZGHFxcXz//fdacv4xMTEoFAotxd+/mv+kfLJAIBAI/j34+fnlcsc7OjpSunRpkpKSuHv3LkqlEpVKhSRJNGnShJMnT8qegOnTp8vGQlZWFgqFAqVSyZw5c9679rZt2/Dy8sLe3h6AqpZG3EvIyLe/a4PWBB70p+q43+X1T5w4gY6ODg0aNNDqe+rUKRYtWoSuri6ZmZk0aNCAyZMnA7Br1y6WL19OoUKFyMzMpFOnTvTt2xeAhIQEfHx80NHRQa1WM3z4cFq1aiXPe+TIEdq1a4eOzsd7v/+/SWUUAkUCgUAgKAhBcakcjUqRZfCz0QEy1Wo292vKsQP7tLIj/k5q167NqlWrcHR0/Ghr/OeNg/93lSuBQCAQfDjRvz077uV4djiY61PV0oiYu6GkpqZSq1atv/28YmJiOHnyJN26dfuo63yQT8LW1jaXYIOPjw979uxh6tSpjBgxIt+xDx48QEdHh+++++6da/Tp04fSpUvj4eGBvb09tWrV0srvjIyMRFdXF6VSibu7O+7u7hw8eFBuX79+Pebm5iiVShyc3ajmoWTv3r1yBOopv/kMqu9JWTMD5m3MO4/2bd68eUOVKlVISkoCwNvbW1a0cnFxQaFQEBoaKvft2rUrFStWxMHBgZ07d8rzhIeHU69ePZRKJZUrV2b06NHyntPSpUtxdXWV51y0aJE8bsmSJcyaNatA5yoQCASCP8f06dNpWasq09rXYWvfhmzt05CtfRviJsViY6KHl5fXP2IYAJQsWfKjGwYASB9AuXLlpKCgIK1jdevWlXbv3i19++230vDhw/MdO2nSJKlBgwZS+fLlJbVanW+/3r17S/Pnz5c/BwUFSQ4ODtJPP/0kSZIkPXz4UDI3N5fb9+/fL5mamkqZmZmSJEnSunXrpDZt2kiPkzKk2YGx0hfrD0vGRYpLswNjpdmBsdKQjUelsfuuSeW9akg9ftogRSVlvPe658yZI02fPj3Pth07dkguLi7y52nTpkm9e/eWJEmSHjx4IJUoUUKKi4uTJEmS2rRpIy1cuFCSJElKTU2VXFxcpIMHD0qSJEmvX7+W50hISJDKlCkjBQYGSpIkSenp6ZKdnZ1WH4FAIBAIPhZ/S7ZCVlYW69evZ9GiRZiamnLq1KkCj1UqlSxcuJA5c+bkmdfaoEEDkpKSePnypdbxay9S0QFSkxIwNDOXj5dx8aSYjS2gcZtce5H63nNYuXJlvpba26IX/v7+DB48GIDy5cvj4+PD7t27AU16SkJCAgCpqamoVCo55zY7pQUgJSVFK0JXX1+fxo0bs3Xr1veeq0AgEAgEf5YPNg66dOmiVSji+vXr7x1z9OhRbGxscHJyeq/yVV54e3vz4sULYmNjc7Xt3LmT+vXrU6JECfnY6dOn+bJZDX5o682WsZ/TYlTeWxlqyFPlKidRUVEkJCRQoUKFPNvOnj1Ljx495GOPHz+mXLly8mdbW1seP34MwIIFC9ixYwfW1tZYW1vTq1cvOXUl+1qcnZ2xtbVlzJgxWm3Vq1fn5MmT+Z6nQCAQCAR/FR+cyujv749SqZQ/+/j4vHeMn5+fXCCie/fuTJkyhVevXlG0aNECrfm2xyApKQmlUsnLly+Ji4vL5YmoU9eHmtM0BsjziDv4fdGBr7aewqyEVe650ahc5ZfBEB0dTcmSJfNsW79+PS1btsTCwqJA17Fs2TK6du3KxIkTefHiBfXq1aNq1ao0atQIgI4dO9KxY0ciIyNp164dLVu2pFKlSgBYWVkRHR1doHUEAoFAIPgzfPRthdjYWA4ePMh3332Hra0tXl5eqFQqtmzZwu3bt2UPxNChQ/Od49q1a1haWmJpaQloCm8EBwfz6NEjJkyYgK+vL2lpvxfBUCgUssqVVUVHiljZ8Cj4Sp5zv61y9TaFCxfWmjsbSZLyFL0oW7Ysjx49kj9HRkZStmxZQBN02Lt3bwAsLS1p3rw5Z86cyTW3ra0t3t7eHDhwQD72sdWwBAKBQCDI5qMbBxs3bqRt27ZERUXJylc7d+7Ez88PJycngoODCQ4OZunSpXmODw0NZcSIEYwfPz5Xm0KhYPLkyVhYWLB8+XL5uI4CWeUqIeYpcY8fYFEu97aADmipXOVFpUqVePHihVxnO5tTp06RmZkpv/Vn06lTJ1asWAHAw4cPOXPmDG3btgXAzs6OI0eOAJq4gtOnT+Pi4gKgJf0ZGxvLqVOnZCUtgDt37uDu7p7veQoEAoFA8JfxIdGL78tWMDExkUqXLi3//PTTT5Kjo6O0b98+rTEqlUqytLSUbty4kWuN3r17S9bW1pK7u7tkb28v1axZU9qwYYPc/na2giRJ0pkzZ6SSJUtKKSkp0rp16yQzMzPJydVNKuXgLFnaVZLaTPxBzlZoNGSCZGZZStLV05cKFykmWVmXll68ePHO627fvr104MABrWNdu3aVpkyZkqtvcnKy1LlzZ8nOzk6yt7eX/P395bbAwECpRo0akpubm1S5cmVp3LhxcubGwIEDJUdHR8nd3V1yc3OTli5dqjWvj4+PdO7cuXeep0AgEAgEfwX/aRGkd6lcqYEmZYzxsHi/q/7q1atMnz5dy83/d3L79m0GDRokF+UQCAQCgeBj8p+ureBhYUQJw0K5VK7sf1O5KqhCYrVq1Wjfvj1JSUmYmpp+1HPOi6ioKFauXPm3rysQCASC/0/+056DnLyvtkKVKlXIzMzUOubs7CyX1xQIBAKB4P+F/xvjQCAQCASCP8P/UwG///S2wsfk/+mPRCAQCP6f+X8s4Pe3yCcXFFtbWypVqoS7uzsVK1akTZs2XLx4EdAIDikUCq0iTAcOHNASYcqu4Z2TdevWoVAoWLBgAStWrJB1FYoVK0bp0qXlz6dPn2bSpEly8SOlUsm2bdtyneNntepQqpwdPwXHsfjmS+aFxBPwIJHoZFWuvgAhISG0aNEC0KQvent7ywWjmjZtSmRkpNz3ypUruLu74+DgQP369Xny5InctmHDBvncPDw8OHTokNx26NAhPD095aJNGzZskNs6deok30OBQCD4t2Fra4ulpaWWpPzp06dRKBSMGDEClUrFsGHDcHZ2xt3dHScnJ+b+9BPnLl/F/bfv8rJly8oF+ZRKJXPnzuXatWvUqFGDwoULy+nmeREYm8qW8AQifjMMDs3/luCju4lIyGBzeAJBcamkpqbi5OSk9fxRq9WMGTMGFxcXKleuTL9+/cjIyJDb586di4uLC05OTrRr147Xr18DEBYWpqVCbGtrS7FixeRxtWvX5uHDh3/V7c2ffzJV4m3eTpXctWuXZG5uLl2+fFlat26dVK5cOcnW1lZKT0+XJElTdKlu3bpyf0Dy8vKSrl+/Lh+rVauWVKVKFa1iTpKUu8CTJEnSq1ev5P+Pjo6WTE1NpdjYWPnY7suhkqlFScnSrpI0YNUeOT1yzm//DYx9k+uamjVrJv3yyy+SJElSVlaWlJiYKLfNmzdPat26tdxWoUIF6dSpU5IkSdLcuXOljh07SpIkSfHx8ZKpqan07NkzSZIk6dy5c1KJEiUkSZIktVotFS1aVAoJCZEkSZPqaWBgIK8TFBQk1a5dO4+7LRAIBJ8+5cqVk7y8vKSdO3fKx7p37y5VqVJFGj58uDR37lypQ4cOkkqlkh4nZUg/346RRu44J80OjJW+D4yVdt1PkH5avkZq06aN1rxRUVHSlStXpBUrVuRqyya7gF/2z4QjoZJleQdp1o0XWsf7Dh4q9e/fX3J3d5fHrlq1SqpXr56Unp4uqdVqqX///tIPP/wgSZIkHTt2THJ0dJS/p7/77jtpyJAheZ7D0KFDpS+//FL+vHv3bqlnz55/4E5+GJ+U5+Bt2rdvz+DBg/nxxx8BTREmT0/PfAWTAPr27cvatWsBuHfvHiqVCmdn5wKtV6RIEfn/k5OTkSRJLqkclaxiwco1eDTvRNW2Pbi25/dAxew0yaNRKVoehMePH3Pr1i1q164NgI6OjpztIEkSiYmJKBSaLYkbN25QqFAh6tWrB8CgQYPYv38/aWlpqNVqJEmSS0a/fv0aGxsbeR2FQiFbnYmJiRQvXhwDAwP5nsXGxnLnzp0C3QOBQCD4EJKSkjAxMdFSiz1z5gxGRkYolUrc3Nzw9vbm8uXLcvvUqVMpUaIESqUSR0dHunTpwqtXr+T2pUuX4uLigqOjI8+ePZOPPX36lPr167N9+3YePXrEgQMHCA8Px9LSktBXKraEJ/A4TQfLCpUBjTx+REIGpyKecerMWdRqNWlpabRt25b69eszYMAAFi1aREpKirz2rFmzqFSpEjo6OizZvEPLvb5xeDdSXr9kcdd6LOnRiIgrv3D/ylnuPHyMl5cX4eHhuLu7o1QqOXjwIA0bNkRfX5+xY8diYmIie75DQkKoVauW/Dxo3ry5llc8m7S0NLZs2aJ1b1u0aMHhw4flIn4fi0/aOABN0aVbt27Jn2fNmsWcOXNITEzMs3/79u05dOgQaWlprF27lr59+37QeosWLaJSpUp4enqyatUqWbL58rNkAvf749WmGx4tOvHrL0dJS9I+h7erPJ49e5aqVavmWqNhw4ZYWVmxY8cO2dB5u2CTqakpZmZmPH36FAsLC1asWIGnpyflypXj888/Z/369YDGMPD396d9+/aUK1eOWrVqsWHDBvT19eW5RNEmgUDwsfD398fLy4uAgACSk5Pl45UqVSI4OJjQ0FB69uwp19fJpnv37gQHB3Pz5k1UKhUzZswA4Ntvv2Xz5s0cOXKEO3fuUKpUKQYMGEBkZCSxsbF4enoyevRohgwZgrm5Oc+fP2fPvv00reZOwHcjCTq6G3VWlryOGrjzy1FMS5Xl6RvN8YEDB3L37l1CQkLw8PAgKChI7t+wYUMOHz5M7Tp1ePYmU0sjR9/YlA7fLmTYtjO0/+Yntozry8EF02gw5nsmT56MlZUVISEhbN++nV9++YU9e/aQmJjIyJEjWbNmjbyN7OXlxYkTJ3j+/DmSJLFly5Y8qwsHBARgZ2entV2hp6eHq6vrR9e9+eSNA+mtZIpKlSrRunVr5syZk2d/IyMjmjRpwo4dO9ixYwddu3b9oPWGDRvG3bt3uXjxIrNmzSI+Ph6VWuLAwUMUtS6LZXl7jIsWp6J3HYKP7NIa+3aVx/yKNp04cYJnz57RpUsXZs6c+d5zSkhIYOHChVy9epVHjx7h5+dHu3btyMjIIDMzkxkzZhAQEMCjR484efIkPXv2JC4uTh4vijYJBIKPhZ+fH+PHj6dOnTr4+/vn2adBgwZaNWdyoqurS8OGDbl79y4pKSn88MMP+Pn5aXlHvb29GThwIAcPHuSXX36RDQ0rKysSEhKYfyKIthPmUKSUDSdWzGHjyN8r5arS04i6GYhZCSuuvUjF0NCQ5s2by17bChUq8ObNG7l/tWrVsLOzQy1pPA85SY5/gUlxTQXgtOQkVGmp+PQdjkJHl9evX8ueAAcHB0qXLk358uWpW7cunTp1omTJkvLzrF69eowZM4aWLVvy2WefyVWFCxXSzhHw8/PLVb8n+7o/9nf6J28cXLt2Ta4/kM3UqVNZtWqV7G56m759+zJq1Chq1KiBmZnZH1rX3d2d0qVLc+bMGTKyJK7v3ULc4/vMaeHJnBaeRAZd4fqe3BoI2VUeIf+iTaDZYhgwYIDsSnq7YFNSUhIJCQlYW1tz/PhxihQpgqOjIwCtWrUiMTGRR48eERwczNOnT6lTpw4AVatWxcbGRssSFkWbBALBx+D27dtERUXRpEkT+vXrh5+fX579du7cia+vb55tqamp7NmzBy8vL27duoW+vj5OTk65+vXq1YtFixZhaGiIvb09arWakJAQWrZuTWQq2FWrTf3+oxm4ei93z5/gTYJmmyL6VhDGRYqjo6ur9fKWzfHjxylVqlSu9XQU8HYemp6hERe2rmBu66psHtMHI7MiHF44jSU9GqFWq7l58yaVKlXi2rVr3Lt3D29vb4KCgrh48SIeHh6Ym5vLcw0ZMoTr169z5coVfHx8sLGx0XpePXz4kMuXL9OtW7dc5/Z3fKd/0sbB3r17Wb58OaNHj9Y6bm1tTf/+/Zk1axYSkKJSa/3Cvb29+eabb5g4ceIHrZez+NH9+/cJCgrCycmJV3EviLj6C2P2XmX8wUDGHwxk4rGbJMY+59m9m1pz5Kzy6Obmxt27d+W258+fa+2r+fv7y8WVsqtVnj59GoCVK1fSqlUrDA0NsbOzIzg4mOfPnwNw6dIlMjMzKVOmDGXKlOHZs2dyTEFERAT379+XSz2DKNokEAg+Dn5+fvTq1QtdXV2aN2/Ow4cP5e+iu3fvolQqsbKyYuHChXz99ddaY7ds2YKHhwc1atTAycmJCRMmvHMta2trZs+ezZw5c5AkiYMHD2JgYICLmwcJsc/lfk/uhGBkXhRDU82DOOHFMwxNfov14veXN9BsU8fExORpjCiAUoULaT0kreydqFClFmP3XaPbnDWYlyzN2D2XWXv+JitXrqRw4cIULlyYhQsXUr16dTk7IS4ujsuXL1O+fHl5ruyX2zdv3jBlyhTGjRuntf7atWtp166dVixcNn/Hd/onp3PQpUsXDA0NSUlJwcnJiUOHDuHt7Z0roK7Hl6NZsmIliuIqFt98KVt4T5JVFCkCw4cP/+C1x40bx8OHD9HT06NQoUIsWbIER0dHfvjhBzxq18fY1Fzef9LR0cGtSTuu7dlC63GzNcfQ5L5m6x7UqlWL6OhoXr58SbFixXj8+DGDBg0iKysLSZKoUKECmzdvlufbvHkzgwYNIi0tDWtra9mr4OnpyaRJk6hfv758btu3b8fQ0BBDQ0NWrVpF586d0dHRQa1Ws2TJErlMdEpKCmFhYTRs2PCD74dAIBDkh0qlYtOmTejp6bF161ZA86Dz8/OjZcuWcsyBSqViyJAhdO/enUuXLsnu/O7du7NgwQKtOZ2cnMjIyOD27dt5PrCzY8i++uorEhMTad68Oc+fRrNh9nAy09PR1dNDv7AxveZtREdH81jXNzQi6zf125wvb+PGjWPBggUYGxtz4sQJbGxs+PrrrxkyZIi8nr25PnE51ndt0JrAg/5UbdeTit51yZgzgWfhd+jlVIeIihWxs7OTvbb29vYsX76cTZs2oVarqV69OsbGxvJcjRs3Rq1Wk5GRQc+ePfnyyy/lNrVazfr169m4cWOuexAZGUlWVtbHf+H7o2kO76vQCMgpfJIkSYsXL5Z69+4tSZIm3U5HR0dyd3eXf5YvX64118mTJyUdHZ1c6YaSJEme1WtJxWxspe/fSifJL6UwODhYat68uSRJkvTkyROpcePGkoODg+Tq6iq1b99ersoYFxendU729vaSrq6uFB8fLz1OypCGbDomlXOvKlnZO0ulHJyl/isC5LVr9xwidZm5QopKytBa+4cffpDTV/4Jli9fLk2aNOkfW18gEPw32blzp+Tt7a117Pbt25KlpaV07NgxrbS+lJQUqXTp0lJAQIAkSZL07bffSsOHD89z3m+++UaqUaOGFB0dLR87deqUdOXKFUmSJOmrr76SmjZtKqWlpcntu+4nyN//b/+M3X9dMrMsJc0JjJUC7idIkiRJP/30k+Tp6Sm9fPky3+vLfp4Fxr6RZgfGSrOuPJVGBVySSju6SxMOh0hfbjwqGZkVkc6EP5EkSZKePn0qj121apXk5eUlV92VJEkaPHhwns+zD2X8+PHS6tWr//Q87+OjbSvY2toyfvz4fNtNTU0JDg6WfwYPHiy3JSQkMGHCBJo3b55r3C/BtwkPD6eQvgH3b2iL++SXUjhx4kTZZaWrq8vkyZO5e/cuoaGh2NnZMXbsWACKFy+udU4DBw6kWbNmFCtWDBvjQuwc14eGg8cz0v8MXef4sWPqV6jSUtEB6vT+kkt+P1LKSPuWDh8+HBMTkw+5dX8pOjo6H7y9IhAIBO/Dz8+P7t27ax1zdHSkdOnSctp1NoULF2bmzJlMnTo1V5D520yfPp3OnTvTpEkTHB0dcXJyYvXq1ZQqVYoLFy6wePFiIiMj8fb2RqlU0q5dO6paGmllFeSkWOlymBQrwbP7v1LV0ojo6GhGjx7N69evqVevHkqlEm9vb7n/jBkzsLGx4dKlS/Tv359WSnuaFcmgvLGCXdOGkZqUwOqBbTi+YArrtvpTt6I1AKtWrcLBwQF7e3v279/P7t27ZS+JJEmcPHmSdu3afeBdzo21tXWuzI+PwR+urWBra8uePXu0Uix8fHwYMWIEwcHBvHr1iosXL/L111/Trl07lixZwvXr11m/fj2RkZEolUo5N/9tevbsSadOnQgICECpVDJixAi5rf0Xo3j5RoWJRUme/BpKlxnLco3Pdu+3szPj8ePH1K5dO99I2Z07d7JkyRLOnDmTq83R0ZHZs2fTtm1b4uLiKF26NPfjk+Uqjws618WzVWduH9lF4UIKoiIfYmFhgZmZGb1792bkyJEfcEcFAoFA8EcJikvlaFQKOqBlKOgAIcf3ovr1KtvXvr+67fTp0wkICMh1fNeuXZQtb/eHZPOPHDnC5s2b5W3kfwN/KuagS5cuWhGTERER8v8rFAq+//57vvzyS1q3bp1rbFJSkpZhsX//fsqUKcPOnTvR0dGhdevWuX5BaapMTuzcSv+VuzEuUoyTq+aSlpSIoal2RkLOlML8tAYAsrKyWLJkCW3atMnVdvHiRV69ekXLli0BsLCwoFSpUlw8tJvOnTtz6cpVpjyOwKe0CQdvhwKaP6rExERZtEkgEAgEfw8eFkaUMCwkv7zlrIHQbUgv9qxPRa1Wy7EI+TFlyhSmTJmSb/sfqaWTkJDADz/88MHj/kn+lHHg7++fy3OQkwYNGlCmTBlZsTAn2dsKOXn+/DkzZszI8y0eYP+Bg7LWACBrDXzWKbfQUXZUan5aA5IkMWTIEIoWLZpn8GJ2FG7OvNO9e/cyfvx4Zs+ejbOzM7Vq1cJA7/eiG1ZWVloZDwKBQCD4+Lx48YLGjRvLnyVAkqBRo4aM/+1lLWfA399Nly5d/rG1/ygfPVvh+++/p02bNnz11Vfv7Xvjxg2ePXsmGxxxcXHs27eP2NhYZs6cyab162StAYDM9DRePY3K0zjIjkrNT2tg2LBhREVFsWfPnlyWZHJyMtu3b+fatWtax93d3Tly5Ij82dHRUUuaWegJCAQCwd+PpaVlrpdNwZ/joxsHnp6e1KpVi+XLl1O3bt139m3RogUxMTHy5z59+sgxBzExMZw+dZIV527xTCqMGk26x/dN3Xh27yalHH4XSsqZUujm5saOHTu01hk2bBgRERHs2bNHS2Y4G39/f9zd3alcubLW8WfPnsliGatXr8bY2Jj69evL7UJPQCAQCATvQqWW/lDcwt/N3yKCNHPmTK3yw3+EDRs20LhxY3wqlspTayAnaqCqpeYNPqfWAJBvtGtO8pOs/LuiUQUCgUDw3yIqWUXAg0TmhcSz+OZL5oXEE/AgUSuz7lPiD2cr/JO8KypVDTQpY4yHxe/u/blz5wLIKYsfg39jNKpAIBD8v2Fra8ubN2948uQJer/FjJ0+fZr69eszfPhw2rZtS7NmzahUqRJqtRozMzOWLVsmq9keOHCAadOmkZiYiEqlonHjxvzwww/vlOoPjE3lQHgsq/q3ZsCqPRgYa9LbdYDwq+dYO6QjP/30k5yZFx4ezsCBA3n16hVpaWm0aNGCuXPnoqOjw8GDB5kyZQo3b97kiy++0BKSio2N5fPPP+fRo0eoVCqqVavGihUrMDIy4sCBA+zbt49Vq1YV6D590vLJ+eFhYUQPe3PszfVlZcTsqNQe9uZahgH8PVoD/8ZoVIFAIPh/pGzZsuzbt0/+7OfnR5UqVeTPOStKtm/fXlZmPHLkCIMGDWLVqlXcvXuXe/fuoaenR8uWLfPVb4hKVnEsOoVL/n44+jSTDQOAN0mJHFn8HQ41G/I6/fdKkmPHjqVdu3ay5s6xY8fkeDd7e3vWrl2b58vuzJkzsbe3JzQ0lJs3bxITE8O6desAaNmyJTdu3CA8PLxA9+hfaRwA2Jjo0c7OjFHuxamb+ZitfRsyrX0dWtaqilKpRKlUMn/+fAD09fX54osvPur5dOnSBWtr64+6hkAgEAj+PH379pWz6BISErh8+TJNmzbNs2/Tpk3lGjkzZsxg0qRJeHh4AJoqij/99BMPHjyQ6+K8zbUXGqG8qwEbUTZtr9W2d84E6vUfhXGRojzOsb2gUChISEgANIWpVCqVHO/m4OCAu7t7rgqO2eOSkpJkWeY3b95oVbfs3Lkza9asKcgt+vcaB9no6SioXtWTkBzKhtk/QoRIIBAIBG9Ts2ZNIiMjefr0KT///DOdOnVCV1c3z77btm3Dy8sLgMDAQKpXr67Vrq+vj5eXFzdu3Mg1VqWWCE/I4OXzJ6QlJ1K8zO+Fl8JO7EOho8CpblMkIDY1Uy4guGDBAnbs2IG1tTXW1tb06tVLNkjexeTJk4mIiMDKygpLS0scHR21dIaqV6/OyZMn3zsP/AeMA4FAIBAIPpSePXuyfv161q5dm0uOOLuipFKp5Ndff2XDhg1/aI2MLAkJSIh5ikmxEvLxpLgYTq+ZR6uxs+RjOStGLlu2jK5du/L06VMePXrEli1bOH78+HvX27ZtG05OTjx79oynT59y7949LU+BlZUV0dHRBTr3T64qo0AgEAgEH5tevXrh6ekpZ6DlJDvm4G08PT25dOmS1lt8RkYGN27cYNiwYbn66+sqNJo7RkZkZqTLx5/cCSEp7gWLfOsB8OZ1PHfOHuU7/Td8P2sWS5cu5d69e4BGw6F58+acOXOGRo0avfOali1bxqpVq9DV1cXU1JSOHTty+vRp+vfvD3yYFo/wHAgEAoHg/w5ra2tmz57NnDlzCjzm66+/ZsaMGbLhkJmZyejRo7G1tdXSvMlGT0eBvbk+luUqkvwyFlVaKgCVazdm0onbjD8YyPiDgbg2bIXvsPF8P0vjSbCzs5MDEFNSUjh9+jQuLi655n+bnONUKhVHjx7VGvchWjzCOBAIBALB/yV9+/bNFUPwLpo3b87y5cvp168flSpVwsHBgfT0dA4ePChr3rxNVUsjdA0Msf/Mh/vXzuXZRwLKmvwuxb9hwwb8/Pxwd3enSpUqNGjQAF9fXwBOnjyJjY0N8+bNw8/PDxsbGznzYuHChVy5cgVXV1fc3d0pUaKEVuzdkSNH6NixY4Gu9V+pc/A+/i0KVAKBQCD47xMUl8qaw+c4tepHei/aKh/PT5vnYxAXF0f9+vW5fv16nsrAb/OfijmISlZx7UUq4W9V5KpmaYRNDqtMIBAIBIK/Cw8LIya2q4fiaTgZKcnoG5vIz6eqf9Pz6f79+6xYsaJAhgH8yW2FzMxMpk2bRuXKlXFxcUGpVDJw4EBev34NaFSnFAoFmzZt0ho3depUSpQogVKplFMtctZU8PHxoXz58iiVSipWrEijRo04ePCg3K5WqxkzZgwuLi5UrlyZfv36ceVJAlvCE4j4zTAAjasmIiGDzeEJBMWlcuDAAQYPHgzAw4cP8fLyQqlU4uLiQqdOnXj16lWua+zTpw8KhUK+JoBXr17RvXt3HBwccHZ2ZsKECXLblStXcHd3x8HBgfr168uy0WlpaXh5ecm5qwKBQCD4b1GlShU5yyH7p3v37oBGm2fJ+KFMrFGOr1yKMcq9OO3szP62F1dvb29q1KhR4P5/aluhd+/evHz5ko0bN1K0aFEkSWLnzp14eXlhZ2dHjx49eP78OZmZmVplmKdOncrr169ZsGABarUaX19fLCwsWLZsGaAxDkaMGEHbtm0BOHPmDL6+vixbtoz27duzevVqfv75Z44cOYKenh7d+vYnoUgZ6vR+d0nO9T18OHroIOXKlSM9PR21Wi1HbmaXbV64cKHcPyAggMOHD7NmzRpevXpFkSJFAGjXrh01a9ZkzJgxgKbUtJWVFWq1GgcHB1avXk29evX48ccfuXLlilz4acGCBbx8+ZLp06f/0VsuEAgEAsFH5w97DiIiItixYwfr1q2jaNGigEadqVOnTtjZ2fH69WsOHjzI5s2buX37NhEREXmfgI4O9erV49GjR/mu5ePjw9SpU5k9ezYAISEhNGzYEH19fRQKBWW86xF0cEe+4wEeBV5Cp7AZ5cqVA8DAwEA2DLKyskhJSdEKKImJiWHWrFnMmzcv13Vfv36dUaNGycesrKwATcnpQoUKUa+eJj1l0KBB7N+/Xy4Z7evry+rVq/OV2RQIBAKB4FPgDxsHgYGB2NvbY2FhkWf71q1badKkCVZWVvTo0UOWqnyb9PR0Dhw4QJcuXd65nre3N7du3QLAy8uLffv2kZiYyJv0DI7u2cWrZ4/fOT7ixkUsHD1kBSrQ5KcqlUosLCwIDw9n2rRpctuAAQP44YcfMDU11Zrn9u3b2NjY8MUXX+Dl5UXjxo0JCgoC4PHjx7LxAWBqaoqZmRlPnz4FNEaEkZGRfB0CgUAgEHyKfLRURj8/P1l16vPPP2fDhg1kZf1eWGLLli3yg/nVq1d07tz5nfPlfNvu06cPTZs2pW7dutT38cGiXAV0dN8dW5n4m0JVtgIVaGQvg4ODiYmJoXLlyqxcuRKANWvWULZs2TzzVjMzM7l69Sq+vr7cuHGDkSNH0rJlS1SqgpXd/BCFKoFAIBAI/gn+sHHg6elJeHg48fHxudqyq1kNGDAAW1tbWrZsSVxcHIcPH5b7dO/eneDgYB49ekR6ejrffvvtO9e7du2aLOagUCiYOnUqQUFBnLtwgZJ2lShpV+md4/UMNQpV+rq5Uxv19fXp27evHDh5+vRp9u7di62tLba2tgC4ubkRFBRE2bJlKV26tLx10KxZMzIyMnj06BFly5bV2h5JSkoiISFBqyDThyhUCQQCgUDwT/CHjYOKFSvSoUMH+vXrJ0fyS5LErl27mDx5MqNHj+bRo0dERkYSGRnJggUL8PPzyzVPsWLFWLNmDUuXLuXZs2d5rnXu3DmmTp3K+PHjAc0DNjuzIOFlPJc2LqZu76/eeb6l7J1If/pA1j149OgRb968ATTZDzt27JDrdW/ZsoWoqCj53AFCQ0Px8PDAy8sLMzMzQkNDAbh69SqSJFGmTBm8vLxQqVRyda6VK1fSqlUrDA0NAU1sw/3793F1dS3QPRYIBAKB4J/gT+kcrF27lhkzZuDt7U2hQoVQq9XUqVOHgwcPMmvWLK2+nTt3ZsyYMVopi9l4eHjQqVMnZs2axeLFiwEYOXIkU6dOJSUlhXLlyrF69WpatmwJaEps+vj4oKOjg1qtZsDgL9Gp0+Sd51qpTmOurJ9PVlYWurq6hIaGMmnSJEBjHHh6erJo0aL3XrNCoWDDhg0MGDCA1NRUDAwM2LVrFwYGBgBs3ryZQYMGkZaWhrW1tVYa5/nz56latSrFihV77zoCgUAg+HfwXxTe+88oJAbFpXI0KkVWnMompwLVmm/H4OPjQ6dOnf6Rc/T19aVfv37vLZ4hEAgEgk+f/7Lw3n+mtoKHhRE97M2xN9cn227L/kX1sDfHw8KI6dOnk56e/q5pPhppaWnUrVtXGAYCgUDwJ7C1taVSpUoolUqcnJyYNm2aLDhUtmxZzM3N5c9z585l/fr18jFnZ2eaNWvG48ea7LY+ffqgr6/PgwcP5PnHjBnD1KlTATh16hTVqlXDyckJZ2dnxo0bh1qtef0MjE3NV3hvkt8OOvbpn+vc8xLV69ixI9bW1rmOQ/6Ce0+fPqVJkyZUqlQJNzc3OnToQGxsrDyudu3aPHz48E/d5/+McQAQ+stxprWvw9a+DdnapyFb+zZkWvs6XDgYAEDx4sXp0aPHP3JuhoaGfPHFF//I2gKBQPBfwt/fn+DgYA4fPsy8efPYuHEjwcHBTJ8+nXr16hEcHExwcDBjx44FkI/dunULBwcHrWJEpUuXlreY36Zo0aJs27aN27dvc+PGDS5evMjGjRuJSlZxLDoF0PZUZ38+umQGFToNJTr59yy2gIAA9PRyexMGDx6cZ3lo0GT6eXh4cO/ePW7dusWIESMA0NXVZfLkydy9e5fQ0FDs7OzkawUYPXr0e4P838e/wjhQqSVSVGotjYK8aN68OcHBwYQEBxMaovlvcHDwezUUBAKBQPDvo1y5clSqVIl79+4VeEyTJk24e/eu/HngwIFcuHCBwMDAXH09PDyws7MDNC94SqWSyMhIrr1Izffh+TDwEkYmZhS3LsO1F5oSzfmJ6gE0bNgQS0vLXMffJbhXsmRJatWqJR/39vaWg+cBWrRoweHDh/+UXP8nbRxEJasIeJDIvJB4Ft98ybyQeAIeJGpZYwKBQCD4/yQsLIxff/0Vd3f3AvXPyspix44deHl5yceMjIz49ttv5Wy4/Hj+/Dk7d+6kafMWhCdk5PIYZPPgxkXKuHqhBu4lZKBSS/mK6r2LdwnuvX1NS5YsoU2bNvIxPT09XF1dOXcu7xLRBeGDjIN169ahUChyLfiuAkyRkZFyTYKc5Nxf6du3Lw4ODri7u1OzZk2uXbv2zv2czeEJBMa+oXbt2rKuQLt27bSKXejo6Mg1rmNiYmjfvj1ubm44OjqyYMEC+Txy7kcplUpZvwAgNTWVXr164eLigouLC61bt5b3dUJDQ2nWrNmH3D6BQCAQ/AV06dIFpVLJoEGDWLt2Lfb29u/sf/r0aZRKJV5eXigUCn766Set9j59+vDkyROOHz+e5/jExERatWrFuHHjcPXw4l0+7GzBPdA8s1atXp2vqN67KIjgniRJDBkyhKJFi8r1gbL5s4J7H5TK6OfnR4MGDfDz86N27dry8X79+vHy5UsuXbqkVYDp5cuX6Oi83/5o164dq1evplChQhw4cID2HTsxdM91IO/9HIAf126ldPmKslzx7t275T7Xr1+nadOmNG3aFIBRo0bh5OREQEAAKSkp1KxZk5o1a1K1alVAsx+1Z8+eXOe1cuVK3rx5Q1hYGAqFggEDBjB37lx++OEH3NzcMDAw4NSpUx/8SxcIBALBH8ff3x+lUlng/vl9x2ejq6vLrFmzmDBhAj4+PlptSUlJNG3alDZt2jBq1ChUagkF5Gsg6BkaocrQBL4rgPNnz3L+3C8cOHBA7uPm5sbevXvx8PDI95zeJbhXsWJFAIYNG0ZUVBR79uzJ9az9s4J7BfYc3L17l4cPH7Jx40b27NlDYmIi8P4CTAWhdevWFCqksVM+++wznj19gpSZ+c4xV3dtxLFRuzzb/Pz86NGjh1y3OiQkhObNmwNgbGxMnTp1cpWRzguFQsGbN29QqVRkZmaSnJyMjY2N3N61a1dZclkgEAgE/17atm2LgYEBAQEB8rHk5GT5RfObb74BQE9Hgb25fr4PTyt7J+IiI9ABHMz1+Xlr/qJ67+JdgnugMQwiIiLYvXu3/KzLyZ07dwq83ZIXBTYO/Pz86NmzJ9bW1tSvX59t27YB7y/ABBrL6+0a1/kxb8ECHGo2RFEof6dGlkrFo5CrKOzccgUppqam8vPPP9OvXz/5mJeXF1u3bkWtVhMbG8vRo0e1gjfOnz+PUqmkRo0acnll0FRVNDU1xdLSkpIlS5KQkMCXX/5eFrp69eqcPHky3/MUCAQCwb+HOXPmaD0bFi5cyNWrVwkICJCfXTNnzqSqpVG+MQeV6zTmUchVMrOyqGr5/jf3Fi1ayC+dzs7Osucip+Cem5sbQ4cOlQX3Lly4wOLFi4mMjMTb2xulUkm7dr+/LEdGRpKVlfWnjIMCiyBZWVlx9uxZKlWqxIEDB/juu++4cuUK27dvZ+bMmYSEhOQ5LjIyEqVSmSt/U6FQ8OrVK614hM2bNzN9+nd0WrYb0+K5ozezSYx9zo9tvJl+8RFfuRTDWO93G2fTpk0sXryYq1evysfi4uIYM2YMQUFBWFpaYmdnR2xsLAEBAcTFxVG4cGEKFy7MnTt3aNy4MTt27OCzzz5j3759bNq0iU2bNqGjo0OfPn2ws7NjxowZgKaqo4GBAampqbJEskAgEAj++7xLeG/37HG0a9KAcf26/yPnNmHCBCpWrEj//rm1FgpKgT0Hr1+/pkmTJtja2jJ06FACAwO5efPmOwswfQj+/v5MmzaNw8eOYfYOwwBA37AwWap0kKRchZT8/Py0vAYAFhYWrF+/npCQEI4fP45CocDZ2VluK1y4MACOjo40b96cCxcuALBq1SratWuHoaEh+vr6dO/eXa6bAJo9HV1d3TxdOgKBQCD47/Iu4b1Vc2dhbfDPiQ9bW1vLVZH/KAU2DhYsWCDvmTx69IhRo0bh5+f3zgJMOVWn3sX27dv55ptvOHHiBBVsy71zPwfA0NQMsxKlMHsdraVjnZ0X2rVrV63+8fHxcoRnUFAQe/bsYciQIQA8efJE7hcTE8OpU6fkvSA7OzuOHTuGJElIksTBgwflypCg2dNxcXEpUNClQCAQCP4bHDp0CKVSSctaVbWE92x+PUE7OzNcy1n9Y4J7oIlH+LPPpQJvK8THx1O8eHH5c2hoKA0aNODJkycoFApmzJjBtm3btAowzZkzh9evX793W0FPTw8rKyt5fpVaov3CHRgXyb9A0cF5U2jiUZlvRg2Tj3399dc8efKEDRs2aPU9fPgww4YNo1ChQpiamvLjjz9Sp04deczevXvR09NDrVYzePBg2XB4+fIlAwcO5M6dOwBUrlyZlStXyvEV06ZNQ1dXVw5UEQgEAoHgv8AnW3jpfYWU3BQvmTqwB1euXEGh+PurYGVkZFClShVOnTr1zmBMgUAgEAj+bXyyxgFA9G8Vr+7lqHjlYK5P1d8qXu3atQtvb2+t9MK/i7t373L//n05RVIgEAgEgv8Kn7Rx0Lp1ax4/fowESBIoFFCsaFGtoECBQCAQCAR/LZ+0cSAQCAQCwf8LKrVERpYmCy9nsP0/wQfJJwsEAoFAIPhrifptCz08xxa6vbk+1X7bQv8nEDl4AoFAIPi/wtbWluDg4Dzbvv32W3R1deWiftn4+Pigr6/Pixcv5GMPHjxAR0eHtm3bAhrRP11dXVlNsXLlyrJoHsDBgwfx8vLCwMCAESNGALy3yGBQXCqdOnXi0qVLACxatAgXFxdcXV1xc3Nj8+bN8vwzZ87UUiI2MzPTKvkMGqmBgiCMA4FAIBAIALVazfr16/Hx8WHdunW52t3c3LTq8qxdu1ar/DOAqakpwcHBBAcHc+XKFZYsWcKtW7cAsLe3Z+3atYwdOxbQeAyORado1n77XH7775rD53gWG0/16tUBjcTyhQsXCAsL4+DBg4wYMYL79+8DMGnSJK219fT06N5dW6Vx/vz5BboXwjgQCAQCgQA4fvw4JUuW5Mcff2TdunWo1dqP7N69e8s6Omq1Gn9/f7p165bvfCkpKUiShJmZGQAODg64u7vLhQavvUh970P46q4NuDdtL39u0KAB5ubmAJQpUwYrKyuioqJyjduzZw9lypTRMl5u3br1zuqUORHGgUAgEAgEaOT3P//8czw8PChevDgnTpzQas9+GF+5coVjx45RpUoVuRpxNtmFBl1dXSlfvjwDBw6UKynmRC1JhCdk5FvAKZsHNy6iX8E9V5FBgBMnTvDq1SuqVq2a57XkLCWgUqkYMGBAgSsJC+NAIBAIBP/3xMfHc+zYMVl+//PPP8fPzy9Xv+zj2YbE22RvK4SFhfHs2TMOHDjAvn37cvXLkqAgu/8JMU8xLl6CjCzt3mFhYfTt2xd/f3+MjY212h49esT58+e1thSmTZtG+/btcXR0LMCqwjgQCAQCgYBNmzaRmZmJu7s7tra2zJkzh/379+cqKti2bVuOHj1KSEgIDRo0eOecxYoVo1GjRhw9ejRXm64CCpKsqGdoRFZ6ulaRwdu3b9OyZUvWrl1LrVq1co1Zt24dbdq0oVix30sQnD17lsWLF2Nra1uAVYVxIBAIBAIBfn5+7Ny5Uy4wGBUVRatWrbSyAQAMDQ2ZP38+ixYtem9xo/T0dC5cuEClSpVytekoFO8tMghQyt4Jg7hIWffgzp07NG/enFWrVtGoUaNc/dVqNevWrctVnfjcuXM8evSIyMjI96z42/kVqJdAIBAIBP8hmjRpgo2NDTY2NhQuXJjbt2/TsGFDrT7du3fPc2uhffv2NG3aNM95s2MOsn/c3d354osvADh58iQ2NjbMmzcPPz8/htZ24ubZI+88T5eGrXh+/Rf587Bhw0hISGD8+PHyGjk9EydOnEBHR+e9Xo33IRQSBQKBQCD4h3hfkcHaRSW+aN2AS5cu5Yot+Jj848bBH5WL/JRkJgUCgUAg+KO8r8jgyZMnKVmyJC4uLn/bOX3QtoKtrS2VKlXScpmEhYWRmZnJtGnTqFy5Mi4uLiiVSgYOHMjr16+JjIxEoVDQpk0brblGTPwGhUJBvwWbWHzzJQOX/EwFF6WWclReRCWrCHiQyLyQeBbffIlXkzbM3nmC6GQVS5cuxdXVFaVSiYuLC4sWLZLHTZ06lRIlSsjnnTOKc+jQoVrXZGhoKI9NTU2lV69euLi44OLiQuvWrYmNjQUgNDSUZs2afcgtFAgEAoFAixljvmJa+zps7duQrX0asrVvQ6a1r0Nx3UxAo23wdxoG8AdiDqZMmUKpUqVISEhAV1eXXr16UbVqVa5fv86lS5fo1q0bb968YfXq1Wzbtg0Ac3Nz7t27R0xMDADXY1LYvPVnrCo6IQEZqW84tPA7mo6ZRc2eQzl98TKVKlVCR0dHS7AhMDaVlVcimNijLXPbVGNuqyrERz9Ct4KSzeEJ6JW2w8zMDEmSUCgUzJw5k6CgIACCgoKQJImbN2/Sp08ftmzZIs87YsQISpQogSRJpKamolar6dy5MwA9evQgMDCQsLAwbt68ScmSJZk7dy6gUcsyMDDg1KlTf+jmCwQCgUCwYsUKgoODCQkOJjRE89/g4GCMjIz+sXP6IONApVIxdOhQhg4dysOHD7lx4warV6/m5s2brFu3jqJFi9KwYUOOHDlC3bp1sbKyksf26NGDjRs3EpWsYtmuQ1hXcsXIvAgAl/z9cGvSljLu1dDRLQRFS7F25z7q1Kkjj8+WmTyy6DvKuFZhzN6rWFaozMsnj1CpVEiSxNhB/fhywmRCQkJYvnw5cXFxpKWlAVCqVCmaN2+ep5pVnz596NKlCyEhIXTu3JlChQqRlZUFQI0aNXjw4AFxcXFkZmaSnJyMjY2NPLZr164FFpUQCAQCwX8blVoiRaXOU7To38QHGQfZ3oJvvvlGdsHfunULJycnLCwsAKhWrRp2dna5xmbLTl57kcqNvVup0ub3h/TVgI0oc8hDmha35IVxKa3x2TKTYcf34t2xNwAvHtzF3LIUDwMv8ub1S1JexRP4+AXOzs40aNAAS0tLnj17BoCVlRUnT57kwIEDLF26lNOnT8tzh4SE0Lx5cwC2b9+Oi4sL/v7+gGbLwdramnLlylGyZEkSEhL48ssv5bHVq1fn5MmTH3IbBQKBQPAf4+0t73kh8QQ8SCQ6WfVPn9of4oOMg4yMDK3CDh/i9rCxsaF0aRv27T/AkzshVPzMB4CUV/GkJSdSvEx5ua8EcmAGaCyx8IQMkl6/JCszE1OLkoBGOaqYTTleP4vGuGhxTC1K8jQ5g+Cwm2zfvp2YmBiuXr0KwODBg4mMjKR169Y0a9aMLl26yFW3vLy82Lx5M+fOneP169fcv39fzgU9duwYxYoVo0mTJjx79owiRYowZcoU+VytrKyIj4+XPRQCgUAg+Di8HffWv39/QJO+V7t2bSpUqECVKlVo0KAB586dAzRVCJcsWYKrqyuVK1fG09OTxo0byy+IOSspuru74+7uzsGDB+U1t23bJsexubi48NNPP+U6r6mLVlLWVJ/jp8/mW1kxJ5IkUbt2bfkZtHbtWlxdXSlUqBALFizQ6hseHk6jRo1wd3fH2dlZfnEFiImJoX379ri5ueHo6Jhr7IwZM6hQoQIVKlRg0qRJH3SvC31Q77cYO3YsBw4c4O7du1y4cIGaNWu+s3+3Xr0Z+uVXVOvYWxaPeJPwEpNiJXL1lYBsr0xGlpSnzKSeoZFWYYxe8zdyeOF0qvy8FFcXZ0qVKsWvv/4KoLXFYWdnh4eHB9evX6dcuXJs2LCB0aNH8/3331O8eHE8PT3lwhirVq2ifv36nDlzBn19fbp3786sWbPkudLS0tDV1UVfX78gt0wgEAgEfwJ/f3+USqX8+cSJE/Ts2ZNdu3ZRo0YNQPNADQkJAWDy5MmcOnWKw4cPy1vC165d48aNG9SrVw/4XfIY4MCBA3Tt2pVXr16hq6tLmTJlOHLkCFZWViQkJODl5YWXlxc+Pj6AxmOwft1aKlSrw9W9WyjnWV0+t+yn09GoFEoYFsLGRA+AHTt24ODgQLly5QDNC+r27duZPXt2ruvt06cPffv2pX///sTGxlKlShVq1apF6dKlGTVqFE5OTgQEBJCSkkLNmjWpWbMmVatW5ZdffuHnn38mNDSUQoUKUbNmTWrUqEGLFi0KdJ8/yHOgr6/PzZs35c9z587lzp07FC5cmG+++YbXr18DGqsoNjaW58+fa43v0L4dtXsNwbtjH/lYIX0DMjPSc62lALIzFPV1FSgA4yLF0NEtRFKcJrCxlL0T8Y8fUKSU5heuU0iPfku3cz0wkPnz5xMbGyv/sURHR8tzx8bGEhwcjKurK6CxRtetW0dGRgaHDh0iISEBZ2dnQGNIXLt2DUNDQyRJ4uDBg1pRo3fu3MHFxeW9SlkCgUAg+OuZNm0akydPlr/rQVMauWPHjiQnJ/Pjjz+ydu1arVixqlWrMnjw4Dzna9CgAUlJSbx8+RKAmjVryi+X5ubmVK5cWUtlcM/lUF49eUzn75Zy+/Rh0pKTcs2pg2ZrPJuVK1dqxb+5u7vj6OiY53Mk57Z3iRIlcHd3l70HOduMjY2pU6eOXFLa39+fnj17YmxsjIGBAZ9//jk///xz/jcyj3MuMGZmZmzYsAE7OzvZrXPs2DHMzc1xcHDA29sbZ2dnnJycePXqFaamplrjTYwMGTB8DEUtf48nMCthRfLLWH49f5zZTd04v2U51/du4Yfm7sTHxQGgp/O7zKRro1Zc2akpmVna2YPEF88o76n5ozi7dgFLOteiqqcHnp6eWFlZyXWzJ02ahIuLC/v27WPjxo0sXboUBwcHQOOa2bp1K15eXjx48IDbt2/Lv7ipU6fy4sULwsLCcHFxISYmhpkzZ8rnf+TIETp27Pght1EgEAgEf5AuXbrIz5/du3dz48YNqlevnmff27dvY2BgQOXKlQs8/86dO6lfvz4lSuT2aN++fZtLly7JSooqtcTOTevxaNEJsxJWVKham9Cju3ONU6PZKlepJVQqFRcuXMDb27tA55O97Q3w4MEDLl68KBsnXl5ebN26FbVaTWxsLEePHpXbHj9+LHsmQPMS/Pjx4wLfhw8yDp4+fcqlS5ewt7cnISEBfX19pk2bxpAhQ5g/fz53796la9euJCUlER8fz/Dhw6lVqxbh4eHyHFUtjWRXy8DVe3Fr3Bb7z3xAkph4JJSp5x5St89X6OsoCA8Pp3///tjY2GCnSEYNNB02hUeh1/ixTTV+PXcc42IlyMrMAKBYGTv0pCxSUlLw8PDgwoULKBQa90O9evV4/fo16enpJCUlMWLECDnNcf/+/fz44488f/6c77//nkOHDsmxFMWKFcPCwoK9e/dy69Ytdu3aJQdfZmRksGvXrnwtUIFAIBD8tfj7+8sxb+3atXtv/+xnAGh0a5RKJU5OTlpSydmSx2XLlmXQoEFaL4DZREdH06ZNG1asWCF7Id6kqwg86I9Xa83LpFebblzbuyXXWNBslWdkScTFxaGrq4uJiUmBrnfDhg1cuXIFpVLJyJEjadCggbzt/dNPP5GcnIyHhwfdunXDx8dHbvuz/CMKiW/LRUbdDOTkqh/5fNFW1ECTMsZ4WOQOdMxLZjLiyi+YFS+BZUXHfMf9GW7fvs2gQYPk4Jac3L17l/v378tuHYFAIBB8PGxtbdmzZ49WzEHt2rXp2rUrQ4YMydU/OTkZCwsLQkJCtIofnTlzhhEjRhAcHExkZCRKpZLXr18jSRLfffcda9eu5ddff8XQ0BDQvBjXr1+fiRMn0rt3b3menQG76dq1KybFLTUHJInEuOd8tfUUVhW1SyMrgFHuxXmTlEjx4sVRqVRahgto4guUSuU7hQCbNm1Kp06dchVWAk3gfYkSJfjuu+8YOnQoZcqUYcKECQAsW7aMixcv5ioklR//yEa5h4URPezNsTfXRwGUcfHEpX4LbHTT6WFvrvWAHzx4sOxC6tuwOpt6N2B59/pkpmn2b+y961Dbyz3XuL+KqKiofHUMKlWqJAwDgUAg+AeZPHkyM2bM4PLly/Kx+/fvs3PnTkxMTBg1ahT9+/fnyZMncntKSkqecykUCiZPnoyFhQXLly8H4NmzZzRo0IDx48drGQYAG9at5fPJs5l4MJDxBwMZfyiIWt2/4Poebe+BDho5ZD0dBebm5pQuXZr79+8X6PpiYmLkwPujR49qbXvHx8ejUmlSJYOCgtizZ49sJHXq1IlNmzaRkpJCeno6a9euxdfXt0Brwt/oOahSpQqZmZlax5ydnVm/abOorSAQCASC95KX5wA0D83vvvuO58+fY2RkhKWlJdOmTaNWrVpIksSiRYtYs2YNKpUKCwsLTExMGD58OM2aNdPyHGRz9uxZunTpwoMHDxg+fDhbt27F3t5ebh8+fDhNmjShYsWKXL7zgEMvf3flP7t3C7/BHZhwNJRCer9nsfWwN5ezFUaPHo2dnR1Dhw4FYP369XzzzTe8evUKPT09TExM2L9/Px4eHqxZs4bvv/8eXV1drK2tWbx4sRwUf/jwYYYNG0ahQoUwNTXlxx9/1BIPnD59OuvXrwc0sRp5ZUPkxz9eeEkgEAgEgn8z76us+PaW9+PHj+nYsSNXrlzJtbXwqSCMA4FAIBAI/iTvq6z4Nrt27cLb21srxfJTQhgHAoFAIBD8RWRveXdp35boKO3UwaJFi2pJ93/KCONAIBAIBAKBFkLWTyAQCAQCgRbCOBAIBAKBQKCFMA4EAoFAIBBoIYwDgUAgEAgEWgjjQCAQCAQCgRbCOBAIBAKBQKCFMA4EAoFAIBBoIYwDgUAgEAgEWgjjQCAQCAQCgRafjHGgUkukqNSo1EKwUSAQCASCf5JC7+/ycYn6rVhFeI5iFfbm+lTLp1iFQCAQCASCj0uBPQeOjo54enrStWtXHj/WFJNQKBS4urqiVCpRKpVMmTIFgHbt2snHlEolOjo67Nu3L9ecgbGpbAlPIOI3w2DLuM+JDLlGREIGfUZPoqhFCXmO7t27y+MOHjyIl5cXBgYGjBgxQmvOmJgY2rdvj5ubG46OjixYsEBuW79+Pebm5vKc9erVk9sOHDjAwIEDC3o7BAKBQCD4z1Jgz8GdO3cAOHnyJM+fP6ds2bIAnDt3jiJFimj13b17t/z/169fp2nTpjRt2lSrT1SyimPRKYCm3nXUzUBSE15Tzr2qXA/bqXF7/FctyeVBsLe3Z+3atezYsYPk5GSttlGjRuHk5ERAQAApKSnUrFmTmjVrUrVqVQDq1avHnj17cl1fy5Yt+fbbbwkPD8fe3r6gt0UgEAgE/4dkV1/U11Wgp6P418xdUD445qBBgwZUq1atwP39/Pzo0aMH+vr6WsevvUjVWvzqrg24N2uv1UfxW7+3cXBwwN3dnUKFcts2ISEhNG/eHABjY2Pq1KnDpk2bCnSunTt3Zs2aNQXqKxAIBIJ/DwEBAXh5eaFUKqlcuTL169dHrVbj4+OT5wsjwIkTJ6hduzYVKlSgSpUqNGjQgJ1HTxPwIJHqbbtRrqI9ZSu7UtnrMw6cvSSP+/rrr6lcuTLu7u5UqVKFo0eP5pq7d+/emJmZkZKSIh+LSlYR8CCReSHx9J65BH1dHcav2Ep0suqd1/bmzRuqVKlCUlISAD4+PpQvX172ks+fP1/u27dv3wLdrz8dkFi7dm35BK5cuaLVlpqays8//0y/fv20jqvUEuEJGbKHAODBjYuUcfHS6hd2Yh9DmtagXv36Ba6B7eXlxdatW1Gr1cTGxnL06FEiIyPl9vPnz6NUKqlRowY7duzQGlu9enVOnjxZoHUEAoFA8HGxtbUlODgYgLS0NNq0aUOnTp3o1q2bvGX89naxUqnk+vXrPH36lCZNmlCpUiWcnJzo2rUrq1evJjg4mF9//RVLS0vs7Ow4e/YsDx8+zLVumTJlaNasGVFRUXh7e3P27Fm+mrWA3aEPiUjIwKl+C0buvMBw/zNU7zWMnl27MP77eXz//ffUrl2bGzdu0KBBA169ekXz5s2pU6cOERERAISFhbFx40bUajWOjo4olUr2Xr0lb7NHBl/h4LwpFNI3YOXUsQz57keC4rRflPv06YNCoeD169csWbKE5s2b4+PjQ0JCAgDz588nODiY4OBgRo4cKY/LaSi8iz9tHJw7d04+AW9vb622nTt34uDggKurq9bxjCyJt3MSEmKeYlK8hPzZu2Nvxh0IZLj/GSZ9O40uXbrw6NGj957PTz/9RHJyMh4eHnTr1g0fHx/Zw9CyZUseP35McHAwfn5+jBo1isuXL8tjraysiI6O/sA7IBAIBIKPSVJSEs2aNaNkyZL4+/vn8kTXq1dPfg4FBwdTpUoVdHV1mTx5Mnfv3mXr1q0UKlSIn376SR4zZMgQzp8/j4GBQZ5rWlhYsHDhQh48eEBCQgLzV/rxq34pXBu2Rg041W2K7m/PFhtXLxJePGX14oW07zuYZs2acfz4cS5cuMDt27cxNjamatWqfP311wDs27cPPT09Nm3aRLly5dh//hp39EoCoMrKYu2Xvvj0GUYZVy9ajZuNa6M2HI1KkT0IAQEB6On9vt2+cuVKevfuTc+ePbWuMS/eDgPIj4+ayujn55fLawCgr6vg7V0UPUMjMtPT5c+mFiXR1dNDAdStXQsPDw+uX7/+3jUtLCxYv349ISEhHD9+HIVCgbOzs9xWuHBhQBNg2bx5cy5cuCCPTUtLw8jI6MMvVCAQCAQfhfj4eOrXr4+3tzerVq1CR6dgj62SJUtSq1YtANzc3HB1dWX79u20a9eOuXPnUqFCBWxsbPIdf+fOHapXr05GRgZv3rwhXsc43wfmhZ9XUcreCVulN7dSNL0UCgXp6emsWbOG8uXLo6OjI6+3fft29PX1admyJeHh4ey5HCrPvXf2WAxNzKjbd5g8v2lxS3TQbLPHxMQwa9Ys5s2bB0B0dDQJCQlUqFABX19fVq9ejSRJTJgwAVdXV7p06cKDBw8KdM9y8sHGwenTp7l69ep7+0VERHD9+nW6du2aq01PR4G9ub7W4qXsnYh7FCF/Toh5ig7gYK5P5P0IgoODc3kg8iI+Pp436RmkqNRcvRHInj17GDJkCABPnjyR+8XExHDq1Ck8PDzkY3fu3MHd3f29awgEAoHg76FLly40bNiQ77//Pt8+p0+flrcUmjRpkqtdkiQMDQ0ZPXo0TZs25cKFCzg7O8tu/rzIyMjA19cXKysrFDo6lKjZQmsrPJuggzsIO76XErb22Lh4ci8hA5VaolWrVlSoUIGvvvqKp0+fcurUKaZPn05YWBgvXrwgPT2dGjVqIEkSP40dSmZWFs8j7hB+6QzWlVz4ecIAntwO4ey6hbyMjkQN3EvIoF//Afzwww+YmpoC8PTpU0qW1HgdrKysMDIyYvLkyfz666+EhoZSu3ZtWrZs+UH3HD4wldHJyYnVq1dTqlSp9/Zfu3YtHTp0wMzMLM/2qpZGWjfapWEr7l38Pa7g6NKZzOtUm2/a1sbX15elS5fi4OAAaDImbGxsmDdvHn5+ftjY2LBv3z6iklXM33uGsvaVKe9QmQ69+zN0wTqyTC0AWLp0Kc7OziiVSho1asTIkSOpX7++vOaRI0fo2LFjQW+JQCAQCD4yLVq0YOfOnURFReXbJ+e2wtvBf5IkMWTIEIoWLcqsWbMYNGgQe/bs4bPPPsszxT4bd3d3hg8fTlxcHGXKluPwoum5+oQe3c3JVXPpt2wnb16/xLR4CSQ0W+erVq3i4MGDnD17lpiYGBo0aMDgwYPx8/PjzZs3WFlZERsbi0JHh+hbgfyyYQmRQZdJTXzFr+eP8zDwMuqsTGIe3GXVwLYAXN29idJlymg9t4yMjEhLS5M/W1lZkZmZCWi8F19++SUPHjwgPj6+ILdbpsDGwZ07d7h9+zZbt26lTJkygOam59y/yMzMZNq0aVSuXJl9+/YREhLCwIEDCQ4ORldXF6VSiaurK5UrV2b6yCEodV/JJ/E47DrBh3eSkZqCDtB5+lLatG9Po/r1uHHjBlWqVMHHxwdzc3NGjx5NdHQ0iYmJJCUlER0djU31RmwJT8DMoy5j9l5lVMBFhm46xo2gEPp/PZ2guFQaNmyIsbExGRkZZGVlERkZiVqtMVECAwNZv349P/zwg2yB3r9/P9d9yBkEApCSkoK3tzfu7u64u7vTtGlTOQAyLS0NLy8vOUBEIBAIBB/GyJEj+eKLL/Dx8ZE1dj6EYcOGER4ezvDhw+UtiVevXvHw4UMqVKiQ77iBAwcyY8YMrl+/TocOHbh38RTxUQ8JO6ExKEKP7eHYstn0W76LIqVs0DMqjCo9HQVw5cI5xo4dS//+/alduzY6Ojr07t2b06dPs3nzZq5cuUJUVBSRkZFEPXmKecnS3Dx1gM869aXDtwuxVXrz9bEwyrh60f6b+STGPCVLpeLB9Qsc2r8PW1tbbG1tAejWrRvPnj0jNVUTsJiamir/P8CuXbsoWbIkxYsXR6VSvdNbkpO/NOagX79+XL9+nUuXLnHz5k2CgoJo1KgRZmZmmJqaEhwcTFhYGKGhoZQqVYqBLRvQ2lKjiKhbSA8nn2a8evIYe3N9etibU6rw7wEXZmZmzJgxg61bt+Za923NhGxUaan8smUFNXz7czQqhQwDE7Zt28bt27e5ceMGFy9eZOPGjQA8evQIY2NjQkNDZQv07T+ct4NAQGO1nThxgpCQEEJCQmjSpAnDhw8HwNDQsEABIgKBQCDIn1GjRvHVV1/h4+NToMD0bIYNG0ZERAQrVqxg9uzZODg4oFQqqV27Nr1796ZNmzYATJs2DRsbG/knPT2d6tWrs27dOsaMGUOvHt1JevGU3TNGY1rcEgD/b74gMyOdTaN6ssjXh8ch13h2NwwHc30GDegPwIYNG3Bzc0OpVLJmzRosLCwoV64cxYoVQ6XSBBeqVRmYmZqSnpwIQKWaDUh48YyEF88AePJrCCXKO6Cnp8eUJWtloyL7JTQsLIxmzZpx6tQpsrKyePDgAdOmTcPV1RV3d3eWLVsme0hUKhW9e/cu0L37y+STIyIi2LFjB48fP6Zo0aKAxqXRqVMn+SIGDx6slR0QHx9PY28l4eHh7C5qiIubGyM71MpT9KFYsWLUqlWLM2fO5GrL1kx4ez8o7MR+yrlXQ99IE0iSWqoydnaabQ5DQ0OUSqV8bh4eHnnqJmSTHQRy+vRpLS0EHR0dee9HkiQSExNRKH4/f19fXzw8PJg2bZrWcYFAIBAUnBEjRqCjo0PdunWpW7fue/tfuHCBxYsXU7lyZTp37gyAs7OzLNI3aNAgbGxsyMzMxMDAAENDQ/mt2tbWli5dumBkZERmZiY1a9Zkyk+LOZ36+zb5zKvPtNZ7Hn6bndOGU9XSiPDwcNLT0/nyyy85f/48enp63Lp1i927d2NnZ0dAQABTpkxBV1eXzMxMfOr4UKGvJpNB38iYtl/PZcOwrkgSRIXdoOvsVajRbMfnxfjx45k+fTomJiZUrVqVEydO5NmvcOHCWkH47+IvMw4CAwOxt7fHwsIi3z4rVqzQ+jx8+HBUKhVGRkboKGDhvB/ZummD3P78+XN8fX3fuW62ZkJe5Zoe3rhAGRdPADmYQ6WW0NNR8Pz5c3bu3MmBAwfk/ikpKVStWpWsrCzatm3LpEmT0NXVBWDAAO0gkLdp2LAhYWFhlChRQmvPKztA5NatW7i4uLzzWgQCgUDwOzk1akDjCRg2bJjWsT59+tCnT59cY2vWrIkk5V/Ib+XKlQVeNxv9uFSORqXkehnVAazsnShvXZJnd4KxqVoVAwMDVq9enec87du3p317bdG/oBxzO1Svh0P1evLcaqBJGeNcasHZ11etWjXat2/PokWLGD9+fL7X9SH8o1UZ3/7FjR07VitXdfDgwe+dIy/NhGwSYp5imkM7ITtQJDExkVatWjFu3DiqVKkCQKlSpXjy5AnXrl3jxIkTnDt3Tt4OWLNmDWXLltUKAnmbEydO8OzZM7p06cLMmTO12oR+gkAgEPz78bAwooe9Ofbm+nI6fnaxwB725qxfsZSYmJiPMveAprW1hJ7erjnUrVs3GjZsSKNGjf7MJcr8ZZ4DT09PwsPDiY+Pp3jx4gUac+3aNXr27Pmn1s3WTMjLQMgOEMlGAaS/SaZls6a0adOGUaNGyW0GBgZYWmr2kooVK8bnn3/O1q1bGTduHKdPn+aXX37R8jK4ubmxd+9erVRIHR0dBgwYgL29PcuWLZOPC/0EgUAg+PezZs0alixZAmieOZIECgUsWbwYG7vaYFLhnUGO78PGRA8bE708ayu8T+fH0NCQL7744g+v/TZ/mXFQsWJFOnToQL9+/Vi/fj1FihRBkiQCAgK0HqCgyR+dPXs20dHRWpbPHyFbMyHiLTlmAKuKv2sn6AA2hTJo1bwNTZs25ZtvvtHq++LFC4oWLYqenh7p6ela571lyxatvgqFgtDQUIoUKcLz588xMDCQ4yz8/f1xc3OT+2ZlZXH//v0CaTQIBAKB4NOlf//+9O/f/6Ovo6fzzxVcyuYv3VZYu3Yt7u7ueHt74+zsjJOTE8eOHZNTDpVKJS4uLri6uhIVFcXFixcxNzcv0Nxv3rzBxsaGTp06cfv2bWxsbJg4cSKQWzMhG9eGrbh3SaOdoAaCd67h6tWrBAQEyG6Z7C2A8+fP4+Hhgbu7O56enlhZWTFp0qT3ntfjx4+pX7++rMCVnaqSzfnz56latSrFihUr0HUKBAKBQPBPo5DeFbHxLyIon0CRDcO6Un/QOPo3rYWHxd/v2vf19aVfv35/2T6QQCAQCAQfm79sW+GfxsPCiBKGhbj2IpV7v2UvKIBh0+diFBf5jxgGaWlp1K1bVxgGAoFAIPhX8a/3HOQMEMlGAubOX0i9unX+8X0bgeC/Rl7BUgKB4L/Fv944EAgEfw9RySquvUiVdUWy06yqWRrlyr8WBoRA8O/mH9U5EAj+q9ja2lKpUiWUSiWOjo5069aNlJSUD5rj5s2bsn7638mUKVNyZegExqayJTyBjSuXsf3bLwGNhy4iIYPN4QkExWm03KOSVQQ8SGReSDyLb75kXkg8AQ8S5Tr0AGPGjGHbtm2AJp25Ro0aFC5cmLZt2+Z5PqmpqTg5OaFUKrWO+/n5YW9vT4UKFRgwYIAsR3vp0iU54NjZ2ZlBgwaRniOlGTQaK/Xr19eqDRMTE0O1atXkojUCwf8zwjgQCD4S/v7+BAcHc+vWLRISEli/fr2W0eDk5MTSpUv/1BofYkAolUqSkpLe22/69OlaKcZRySpmL1vDplG9cmUFZX8+GpXCqehktoQnEJFDsfRtA+LJkyccOnSILl26ABrxsQULFjB//vx8z6dmzZpYWVkBvxsTRkZGDB06lHPnzhEREUFMTAyrVq0CwMHBQTYGssvjLlu2TMuYqF69OuXLlwd+NyaaNGnC/fv3adiwoZYxkZ8REhoaSrNmzd57PwWCfyPCOBAIPjIZGRm8efOGokWLkpycjLW1NcHBwRw+fFhLpRPg22+/pWLFinh5eclv19kcPXqUWrVq4eXlRbVq1Th9WpOmm6397u7ujqurq6zhkZyczOeff46LiwsuLi60a9dOlv/28fFhzJgx1K5dmwoVKmipkfbp04cFCxYAkJSUhG+XLhxZ/B0PAy8RE3FH65x+2biUpT0bs7hbfQZ3bs2rp1HvNCDmr1hNhw4d5DojNjY2VKtWDQMDgzzv3bZt24iIiGDy5MnA78ZE8+bNKVWqFFZWVigUCgYPHszPP/8MaIro1KpVS773qampvHz5ksmTJ3Pu3Dn27t1LeHi4XF3W3d2da9euERwczIEDBwgNDZVFzB4+fCiPe9sIcXNzw8DAgFOnTuXzmxcI/r18ktkKYr9S8F8gu3BLZGQkXl5edO7cWUsXvly5cpQuXZo7d+7QoUMHHj58yK1btwgJCSEyMpJevXqRkJBAtWrVGD58OEuWLOHo0aPMmzeP9evX07hxY0aPHk1iYiItW7aka9euKJVKMjIy8PLy4sGDB7i7uxMaGkpqaiomJiaUKVOGPn36EB4ezo0bNyhfvjxmZmYcPnyYS5cuERERwb59+zh27BhHjh3DxqYMqQo9mnw5mZsn9/Ew8BJlXD35ZcMSLvy8ClVaKg7V69P267ncPnsEvy86YF3ZDVVaKi+jIzEpbkn3uWspbF4UHWDLpo2Y6hfi4MGDWFpasnLlSsqVK5fn/Xv9+jWjRo2if//+WsaEjY0NCQkJWqqjtra2PH78mBMnTvDkyRM6derE5s2bsbCwoEWLFhQuXJjWrVtTvHhx2rdvz8yZM/Hz8wM0xWiycXV1JSEhQfYc7Ny5k9atW8uei8GDBzNr1iyGDh0KQNeuXVm5cuU7pdUFgn8jBfYceHh44OnpyaxZswBYv349CoWCTZs2yX0OHDiAj48ParWaOnXqyBY2aEpFKpVKdu7cme8aUckq+k/9kdYjprD45ku+ORyEy2e1MTM3z7Xf+K59xfftOYaFheHj44OjoyOOjo4EBAQAcObMGYyMjLS0q7PrYgsX4l/DX7EXn5P169fnu1f9MVi/fj2//vprgdbP3laIi4vD1tY2V0GUsLAwoqOjMTEx4dKlS1StWpWvv/4afX19pk2bxsaNGylVqhRbt25lyJAhhIeHo1Qq+f777zE1NaVEiRLcuXMHQ0NDVq9ezdy5c0lISKBq1arcuHGD4sWL8+DBA3R0dDA2Ngbg9OnThISE8Pr1a1auXMmsWbMwNjbGw8ODzZs3M2DAACp/VhevbkOQyivZvHUrVdp2Q6EA3UJ6uDfrQELMM67v3YqNkxJDEzPuXT7N3NZV+GXjEtKSk4i6GUjHaYsZuesCJsUsuLpLU0wt8PAuXsXHsXb9BgIDA+nevTuurq75bnV8+eWXFC9evMAPXrVazbhx41i+fDlWVlZUrFiRsWPHkp6ezpkzZyhXrhzTpk2jffv21KlTh6dPn8pjIyMjcXd3x8rKCn19fZo3bw5oRM5KlSpFlSpVSEpKwtbWlps3b1KpUiV0dHRITEzk5MmTuc7l1KlT6Orqyh4Y0Ai5de3alYoVK+Lg4KD1Xbh27VpcXV0pVKiQ1hiA8PBw6tWrh1KppHLlyowePRq1WuOPWbJkifydLBD8lRTYOAgKCuL8+fPylwxo3nymTJlCRkaG9qQ6Oqxfv56pU6fKtbenT5+Os7MzHTt2zHP+wNhU1oc9Z/eaJVT31chTGhibUnvgeNp/t5zUTG1nZU5XYM59xfe1vXnzhjZt2jBjxgzu3LnDzZs3qV27tjxvpUqVtIo/Zb+dCBfiX0dee/H/Ft42DgpCoUKF6NChA0eOHEGhUHDt2jWUSiWDBg3iiy++wMjIiObNm8v/to4cOUJERARfffUVT58+pWPHjigUCqpXr07btm2ZOHEiYWFhPH36lDFjxshlWO3s7NDR0WHt2rUAmJiY8OTJk1znY2dnhyRJrFmzhpMnTyJJEoUKFeJBTDzOjduSUcgACfis8+ekv0lBrc6SxyoUkBT3HLfGbdEpVAifvsPpu8QfQ1NzRmz/hc869cWhRn2Mi2gUQcu6VSE+OhKA22cOkZmeRu9ePVEqlfzwww+UK1cu30qn58+f59dff2XAgAH4+vpy+/ZtKlWqBEDx4sVlwx00D/eMjAy+/vpruUZKVlYW8+fPx9fXl3v37gFw9uxZFi9eTMOGDYmJiSExMRFbW1uMjY0JCQnh+fPnZGVlcfbsWXnuy5cv06ZNG/k8DQ0NOXz4MHXq1KFIkSLEx8eTlpYm909ISGDChAmygZHNjz/+iIGBARERERw9epQhQ4YQHx8PgJeXF9u3b6dbt2657sPYsWNp166d/J107Ngxjhw5AsDAgQPx8/MjISEhz3soEPxRPijmoHDhwgwfPlz+rFQq8fT0zDOoys7Ojm+//ZZ+/fpx/fp1Nm3alEuPIJuoZBXHolMIO7Gfsu7V0DfSfEkWNi9KOY/P0DcyJkml1op4Lly4MHp6mvSp7H3FbNfju9q2bt3KZ599Ju9J6urqUqLE75Ub30W2C1Hw15BzLz6bH3/8kWrVquHp6UnTpk1l4zIjI4OxY8fi4uKCu7s7TZs2zXPOuXPn4uzsjKurK927d5e/NKdOnUrnzp1p1aoVDg4OtGzZkps3b9KkSRMcHBzo2rWr/DaWlJTEgAEDqFatGm5ubgwcOJCMjAzWrFnD9evXGTlyJEqlkkOHDgGavf2uXbvi6upKlSpVePDgAQBxcXHUq1cPLy8vevbsSVpaGoUKFcLU1JQFCxaQlpaGn58fT5484cGDBzRs2JCff/6Z5cuXo1KpiI2NxdTUlODgYK5fv86hQ4c4ceIEa9asoXz58gwePBiFQkFmZiaSJMmG6/Hjx/nmm2+oV68earUaSZJk70ydOnWYOHEiarWau3fvcuHCBa5fv07s60Qiop9x5+xRJCA18TVzWmjKnW8e3ZejS2aSGBdDyJHdZGVmcmbdQlTp6Rz4cRKB+7ehzsxk9cB2XNy2mpsn93PrtObeKHR0ub5nC8eWziL80hkUCh1q1q7LtcAgwsLCuHnzJq9fvwY02wg1atTAzc2NatWqsWXLFlxcXFi4cCHJyckUK1YMExMTKlasiLGxMc+ePeP58+d069aNbt268fLlS3r16kWpUqXw9fXl119/JSEhgcGDBxMfH8+jR4/YsWMH3t7emJiYoKenh76+PpGRkfJ3QEpKCvr6+nLZ9bJly3LhwgX5oR0ZGUnFihWxs7MDNB5RXV1d9PX15b/BL7/8km+++SZXATp/f385tqN8+fL4+Piwe/duQPNC4+joiI5O7q9khUIh/x2npqaiUqkoVaoUAPr6+jRu3JitW7fm+e9BIPij/OmAxFmzZjFnzhwSExNztQ0aNAg9PT0aNWrEihUrtB4CObn2IhUd4OGNC5Rx8cx3rWsvUrU+Z7sCLSwsMDc3Z8iQIe9tu337NgYGBrRs2RKlUkmvXr2IjY2Vx92/FC6PrgAA6KBJREFUfx9PT0+qVq2qVVkRoHr16nm6EAUfRpcuXVAqlVhZWaGjo0Pnzp0BjeF29+5dLl26JLuds39vs2fP5t69e9y4cYOQkBCt7axsDh8+zNq1a7lw4QJhYWEYGxszYcIEuf369ets3LiRu3fvkpSURP/+/dm5cye3b9/mzp07HD58GIDRo0dTu3Ztrl69SkhICGq1moULF9K/f3+qVKnC/PnzCQ4Olt8Mr127xqxZswgLC6Nhw4bMmTMHQH4zTE9Px9vbG1tbWzIzM6lVqxYtWrQgJSWFQYMGUbp0aRwcHGjevDm6uro8fvyYlJQUWrZsSUJCApcvX+bly5dYWFgQHR1NbGwsurq6rFmzhgULFpCSkoKDgwO3bt0CYNOmTVy/fh0nJydAs4/u7e0NaB7AYWFheHp6smDBAgoXLoyhoSHPXyVQxMqG9JRkMtI0/87SU5KwLG+PQ/V6ZGakE30ziDIunpgUtSBLlYFj7UY0GTaZkKO7SYx9RmxkOKWdlFSu1Yhd00fw6mnU778chYLWE+ZgXMyCzZs28s3hILbf1bw1Ozs7M2rUKH755RfCw8MZPHgw8+bNo0OHDjg6OvLgwQNSUlIwMjLixo0bLFmyhEOHDlG5cmVq1qzJxYsX6dChA6mpqUyZMgV7e3uMjIzQ19dHR0eHXr16ceXKFfbt24evry9DhgyhcuXKjBs3jqysLBYvXixnIBw4cABLS0vc3d0Bzb/55ORkjI2NkSSJFStW4OvrK19WdHQ0Li4u8kN9586d6Ojo0Lp161x/n48fP9aKr8iOk3gfCxYsYMeOHVhbW2NtbU2vXr20itmJ7yXBx+BPGweVKlWidevW8hfi24wZMwYbG5t83/RUaonw3yoqJsQ8xbR4/m/x9xIyUKl/12yytbWVXYHZlRTf15aZmcmJEydYuXIlQUFBlC5dWi5z6enpSXR0NIGBgezevZsVK1awfft2eU4rK6tcLkTBh5PfXvyePXs4ceIEXl5ests5+8vzwIEDDB8+XI5qz8vbc+LECbp06SLnrn/xxRccP35cbm/cuDFFixZFoVDg6emJj48PpqamFCpUCA8PD8LDw+XzmDt3LkqlEg8PDzlSPT9ypsVVr16d+/fvExkZSXBwMLVr10ZXV5fo6Ghu3bpFRkYGkyZNYubMmejq6mJsbEz9+vUxNDQE4Pnz54SEhFC8eHF27doFQK1atRgyZAhGRkYcOnSICRMmoFAo0NfXx9jYGDMzM9LS0uTAujlz5hARESHfu5s3b8qZD2fPnpVT9b777jsiIiIobGxM7+V78GjRGdMSJfn17FFCju4GhYI+i/3pNmcNLUZNx8DYBK9WvnSZuRyFjg4Xt63h2u7NVKxWB4Dxh4Ip51YVQ1NzbJXeRAZdlu9R1bY98GjekVo9vgBJzfK+zfmqeU0Afv7lOmfPnqVs2bLExsYyZMgQatWqRcmSJXF3d2fTpk2abY8HDzh58iRt2rQhJiaG0NBQ0tPTqVq1KiEhIXh4eLBmzRrS09MpWrQoKpUKU1NTFi1ahKOjI61bt+bs2bPUq1ePI0eOsGvXLsqVK0dAQABFihTB0NCQAQMGoFAoGDNmDKDxLFpZWVGzZk2KFSvG/v37ZUMLNJ6qBg0ayL+7GTNmsHDhwnz/Vv4Iy5Yto2vXrjx9+pRHjx6xZcsWrb9rKysroqOj/9I1BYK/JJVx6tSprFq1imfPnuVq09XVRVdXN9+xGVmSnBOtZ1QY1VtiJTmRfuv/NiYmJvj6+uYSbsmrrWzZstSrV4/SpUujUCjo0aMHly9rvsTMzMzkKpE2NjZ07dqVc+fOyXOlpaXlciEK/jg59+JBI0wzceJEeW81LCyMsLCwPzx/9lZSNtkPYND8Xb79OVv8RpIkdu3aJZ/H3bt337mdlN888+bN48WLF1y5coXQ0FC6detG3759USqVjBgxgoMHD1KqVCkiIiJyxe0YGhpy6dIlvvzyS0aMGEF4eDgZGRkYGhoydepU7t69i6OjI3379pU9BoGBgWRlZREcHExERATfffcdOQVQy5Urh76+Pra2tty4cYPQ0FC+//57Kto7oPPbNlxhsyJ8dzmafst2oKOri7mlxn3t1borxUqX1QQdAAaFTRjuf5bZ24+wfcNadBQK6lkZ0GDQWFqMmi7f+xq+2uVta3UbhK3HZ1Rp3Y2RO88DcPLJG56/UfE22UZceHg4hoaGKBQKPDw82L9/P6CJA9q2bRuBgYEcOnSImzdvMm/ePKKjo/Hy8tKKj0pOTiYgIAAdHR1SU1MZOHAgzZo1IyIiglWrVnHp0iUePXrExo0bqVKlivyAL1y4MEZGRvz8889Ur16dcuXKyVuWarUahUIhP5hv3LjBs2fPUCqV2NrasnPnTqZPny5Xdy1btqy8TQYa72bZsmXz/bvKZunSpfTu3RsAS0tLmjdvzpkzZ+T2tLQ0rcwNgeCv4IOMg9TUVBYtWpTruLW1Nf379/9DUbP6ugqyv8KtKjoR9yj/NzTFb/0BIiIiZFdgRkYGu3fvxs3N7b1tnTt35tq1a/I2yKFDh2QX4rNnz7T2nQ8cOKDlvrtz546WC1Hw5zl16pQcZNa2bVtWrFjBy5cvAc1+blBQEACtW7dm4cKFctZJzq2gbBo2bMj27dvl3+3KlStp3LjxB59T27ZtmTNnjvyQf/Xqlew5MDMzK3Dw16tXr7CystK47Z8/Z8eOHXLb3bt3KV++PAMGDODrr7+WDdSGDRuyevVqAF6+fElAQACdOnWiUqVKxMXFMXr0aJo0aYKLiwsqlYqrV6/StGlTChcuTIUKFWTtg6dPnzJq1Cjs7e21NBOy5y9SpAjffPMNQ4YM4frVK9w9//ub6ETPEvyPvfMOq+Lo4vB7gUsXBEREQRGkSEcQu6JgQ429xYq9JPYWjd2oiUaNJTEq9oYVjRo1drErAipEUcFeEJXeme+PGzZcwZYviSbZ93l4dHdmZ+fuLXv2zDnnl5maQn5uLisHtWdem5rMbenLk1u/UtrGgZ6OJSE3hy99LZnYoiYj+3TD1dWVb4f1YV7r6nzb3IvoY/vZPm0Yk2qoagl836MxiffiCFv/A/ER57h2bB8/9m4BqH6EXhiXJz8/X3oiPn36NI8fPyY+Pp5atWpJRo6pqSk1a9ZUu8YlSpTAzMyM7Oxs5s6dKwUEKhQKMjIyyM7O5ueff6ZKlSo0aNCA2bNnM2jQIDZt2sTDhw/R09PD3d0dCwsLunbtStWqVYmPjwdUntEnT54waNCgIgZiZmYmffr04ciRIyQlJdGsWTOePHlCfHw88fHxtGvXjkmTJkmy8O3bt2fp0qWAqn7CsWPH3inTxtbWVjKg09LSOHr0KK6urlJ7TEyM9Bsm888lJ1+QlpOv5h3/kLzzXa5g3TI9Pb3Y9nHjxhUbd/A2lBoK7I210QDcAlpw48xRqS07I51ZTdzZOKY3T2/f4JtADyZNGA+obipeXl54eHjg5eWFhYWFVCjlTW3ly5dn/PjxUuDTkSNHpC/s9u3bcXNzw8PDg+rVq9OwYUOCgoKk+ezfv/+12RYy705BzIGrqysxMTHSU1qXLl3o2bMn9evXx8PDA09PTynIbuzYsTg4OFClShU8PT2lJ6nCNG3alKCgIGrUqIGbmxvJycnMmjXrvec3f/58KaXV3d0df39/6WbRr18/Zs6cqRaQ+DqGDh3KuXPncHFxoVu3bgQEBEhtixcvxsXFBS8vL7788ku+/fZbABYuXEhMTAwPHz6kb9++TJgwAX19fX799VeUSiVRUVGsXbuW6OhohBCsWbOGffv2cfPmTXx8fGjUqBEuLi7Ur1+fXbt2cenSJS5evCjNv2/fvtjY2JCUlMTmzZvp27cv9vb2HJw/qcj8tfUMeHj9ChpaSjSV2nz6dTDu1ubcvRVLVlYmlSpVolWbtvhUq4GOri67du0iI/EJLxOesPj770lMSadm574AVG3djVWfdeTg97NoM3E+w7eG0Wiw6rt8dPUihrX0Q1dXl1atWqGnp0dAQADfffcdZ8+exc/PDy2t4kuyNGnSBEdHRxwdHalVqxa3b9/GysoKTU1NFAoF3bt3x93dnREjRlChQgU2bNjAzZs3adeuHQ8ePKB169ZSxgCobr4rVqygZcuWgMqDY2FhQe3ataWiScuXL8fKyorIyEiWLVtGcnIye/bsedvHitGjR5ORkYGdnR2NGzdm8eLFlCpVClBlwVhZWbF161amTJmClZWVZBivWbOG4OBgPDw88PHxwd/fXy3uQf5d+mfzLiXHPwjiI+BuSraYFZ4gZoUnCMfaAWLQuoPSduG/eynZH2yOWVlZws3NTSQkJHywOcj8d6hQoYJwcHAQHh4eokaNGmLr1q1i3LhxQktLS/Tq1UsIIcSSJUuEsbGxUCgUQldXV+jq6gotLS0xffp0MXz4cDFlyhSRk5MjpkyZIqytrYVSqRQeHh6iU6dOQldXV9y+fVtoaGgIR2cXAQhzm0qi4aBxAhBDNh8TWjq6QlOpLRQKDVGpmp+YcChaNOvaS0yfPl20+7SbGBdySMy8+ERMOhYrNJXaovu8tWLGvIXCwsJCnD59WqRm54lu89YKQIwMPSeUunpCS1tHWDq4CEsHF2FW3lZoaCmFlo6ucPZrKlKz86TXv2rVKmFkZCQMDQ1FhQoVhJ+fn9S2adMmYWdnJ3R1dYWLi4uYO3euEEKICRMmiBEjRogmTZqIuLg4YWxsLB0zd+5c0a9fP2k7LS1NaGhoiJycHGlfVlaWaNasmfj888+lfQcPHhS1a9cWzZo1k96Xy5cvq71XnTt3Fj/88MP//6b/Aa5duyZq1679Qc79b6Xwd8/Dw0P07t1bTJ48WQDixIkTUr9FixaJHj16CCGESElJEY0aNRJmZmZqn7u3MX/9NuHbtof4OjxBDA05Lmy8qgtzm0rCws5JeH/SWZy+myj1PXv2rHB3dxf29vaifv364v79+1IbIFxdXaU5F8wzKipK2ufh4SEqVKggTExM3mluH4V/3NpQSWNr1fpgy9EzSU383WVcMMHG1gZFlN/+TuLi4pg9e7Zk6cv8u7CxsSEiIkJtn5+fH6Ghoe81TqlSpaSn9P+XgsDN06dP065dO65du4aFhQU7duwgNTUVIQTe3t64u7uTkZFBTEwM06ZNY/r06VIMg42NDceOHePHH3+kbNmyXL58mdq1a6NUKlEoFOgblqDzMtVT76A1BzgTEiydX0NTk/4rf8K9USsykl/yfad6XDi4h/V7D3E7ORtjOzcUGhpSHIJjrQCOxNwhKzeXnJwchg4eKI21Z+6XmFrZoGdkgrWbD0M2H6P7gvWUc1KN8evJX6QlwwLq169PQEAA1tbWHDt2TEp5tLa2pk8fVSxDRkYGEydOZOvWrRw/fpyQkBAOHjxIpUqVSEpKwsDAgJiYGGm9f9++fVSpUoUqVaqgoaEhxSLl5ORQsWJFNDQ01AIKjxw5wu3btzl79iwVKlTg/v37BAYGSnEP8GHX/O/duyenV/8FFHz3IiIiWLFiBUCxhcwKUCqVjB07lkOHDr3zOe6l5jB7ykT8goaSD2jp6PDJ2NmM2HGGIZuPkZ2RzsQZs7mfmkN+fj5dunRhwYIF3Lhxg8DAQIYNG6Y23smTJ6U5F9TucXNzU6vb07x5czXdlDfxtxsHK1asUKtAWPCXGnORrvbGVHd1xLmuap24QBK2q70xXqU+bMCNo6NjkaImMjLvyp+h9BceHo6Pjw9169YlJCSExo0bEx4eTkZGBrm5ucTHx7N06VIMDAwICAhgw4YNJCYmsmXLFkl3QKFQ0KxZMzQ0NHiYlkNuofXN7Mx0CqKDS1paMfqni5hZVcTW3p7GfrVxsq/E+Jnf0Hj4NG6cOUJy4lMAzm1bjZ1vHTSUSm5fPIWemSXdh4zm8C8HES+fUqqCHaUq2OFUpxEpiU+o0kyVulqyjBVVWnTCr8dnKBQUWypdqVSSmpqqtq9GjRosWrSIcuXKcevWLWxsbPjmm284efIkly5dYtKkSTRp0kRKYf76669p0qQJ4eHhdO7cmdWrVxMQEEDPnj3p378/L168oHTp0qSmpnL48GG8vLzw9PSkS5cuzJo1iwcPHvDs2TPu3LmDlZUV+/bto0WLFtJ8PuSaf+PGjaWUVZm/lk8++YScnBypNkVhdHR0iqh8vo01ew+jZ2iESVnVclWp8nZYOrgAKsPcysWLl4/ucuFpBpcuXUJLS4v69esDqjIBP/3003tlzmVmZrJhwwZ69+79Tv3/dm2FPn36SFZ/cVgZKmVtBZmPhvT0dCwsLIiLi5NSBT/99FPq1KnDwIED2b17N2PHjkWpVBZJ17WxsaFjx44cPXoUe3t7fvzxR4YMGcL58+cBVYDa5MmTAXjw4AFDhw7l+vXrKBQK6Sn56dOnDBgwQKqImJyczLBhw5g9ezbTp0/H09OTY8eOoaOjIwXTWllZsXLlSjw8PIiNjaVevXq0adOGpKQkKleujEKhICUlhaPXbpOVnsp37VWpiLMau1OyTFlp/tFH9vHTnPFoaCjI+y0tMN24HGXtnGk6dApLg5qR+jwBDU0tTMuV59aFMBLiY7Gwc2LskjX08anI3B+WsyXhMY0Hj+fw8m9R6uqz+5svyM/LIy8nG6c6DTE0M6e4b/nJkydJS0tTizdIT0+nYsWKJCYmoqGhQZkyZUhKSiI/P5/MzEwsLCwICgqSShBXq1aNxYsXU6JECZYvX06bNm0IDAzEx8eH0aNHs2/fPnbv3s3Lly9xd3fn+vXrZGZm4u/v/06KmfHx8eTl5ckBgf8yCnRRAOk7qlAomD17Np999lmxdSzeh5x8wYnjx7F28y62PTsjjYuh62n82ZfcSMomO/6OWo2MEiVKYGRkxMOHD6WCXP7+/uTm5uLv78/06dPVsnUAduzYga2tbREpgtfxUSwrvIpSQ4GBUkM2DGT+VgoCJQv+Ll68iL6+PgEBAaxfvx6AJ0+ecOjQIbp168bTp08JCgpi+/btREVFUalSJbXgNoDExETOnTvHhg0bmD59OllZWURFRXHu3DlCQ0MJCQkBoGvXrnh7e3PlyhWioqIkHYXPP/9cqiXy+eefExsbi6mpKXFxceTk5KCvr4+Hhwd5eXkcPXpUqrI3ZcoU2rdvj1KpZOPGjYwcORIhBOHh4URHR/M8KZnnSiO09QzITE9laMhxJh69DgoFxqXLomtoRKkKduTn5eLWuA16+gbk5uWz8tuvEICNpy+GZqUZf/AaU07e5tNvVhIyoT+ZqSl0/noFL5TG5Ar4edtmlu/Yi1JXj4T4WIzMSvP5xsMMDTnGiB2nCRw+FUfjooqMzZs3p1q1auzbtw9vb9UP6IULF9DX1+f777/H39+f27dvU6JECdauXYuxsbGklVCmTBlevnzJgwcPWLx4sRRc2LJlSw4cOEBmZiaXL1+madOmrFmzhh49eiCEIDIykk8//ZTPPvvstYZBfHy82o/r0qVLGTNmTJG0WZl/NoWXFVq3bi3t9/f3x9raWipR/kfJzhMkPXmIoWnRei25OdlsHNuXStX9cGnQDAFqHr7iuHPnDpcuXeL06dMkJCQwevToIn2Cg4Pf2WsAH6lxICPzISj8gxARESFJKQ8dOlS6WSxfvpzOnTtjaGjI2bNncXd3l9y6vXv3LlIDo2fPnlSsWBFHR0cWLVpEWFgYXbt2BaB79+788ssvpKamEhYWxsiRI6Xjrl27xv79+zl06BC9evVi3bp1bNu2jaSkJFq0aEF6ejqpqalFvBXa2tpUq1aNw4cPU6VKFXJzc3n58iVGRkbY29vTtWtXfvzxR54kJKKlrUN+Xh5lKlWmjL0zj2OjsXL2IvVFAslPH5Hy7AkiX1DSohwubm706tef57/pJFw/fYTn9+JY1qcFCzv5sXFMLxQKDbS0dcjNykIACc9fEhUVxbi+3fm6WRVunDrMi8f3WNG/zVvfi9DQUGxtbWnQoIH0Q3zu3DmpPTMzk4CAAL788kvat2+vdmxBPRI3NzeEEAwdOpS9e/dSpUoVGjVqRP369blz5w6HDx+mW7duPHv2DFB5aUJCQoqka8+YMQM7Ozvs7OykmgWgMlZCQkIYMmRIkZTEtLQ0goKCcHNzw8nJiXHjxknpmLKI24fjz0gXnD17NtOmTXtt5t67oK2pQKmrR062el2fvJwcNo3ri5G5BS1Gq0oDKABbmwpqNTJSUlJISkqibFmVp6+gXoaBgQGDBg1Sq88Dqpi5s2fPFqvd8Tpk40BG5i34+vqir6/P0aNHWbZsmSTX+yrFPT0aGhoCKsOjcuXKrFq1ShKbetPT5rFjx6Tc9kOHDmFra8uDBw/o1asXI0eO5OzZs6SmpkoFeQrIy8vj0qVLODo6UqlSJfT19Zk6dSopKSmcPXuWoUOHcvToUerW8OX+1XC1Y2+eO86dyPMoFIV+Fn6boq+PNz27dyM/7zcRJiGoVL0eQzYfk/6+OHCFso6uPLtzk/y8PPzr1eXzSTMYsusiY/eGY1OlBmZWFenz4w618x46dYbc3Fw1r83IkSPZsmULNjY2+Pn5Aao0z8uXL6Ovr8/Zs2cZO3YsPXr0KPJDGRMTg6GhIcnJyfzyyy9oaGhgb2/PqFGjKFmyJOXKlQOgatWqaimD/fv3l4ISCzhx4gSbNm0iKiqK6OhoDhw4wN69ewGwtLQkJCSE+fPnF3n/Zs6cSV5eHlFRUVy5coXIyEhJhVEWcfv7+TPTBatUqULt2rX54Ycf/vB8lBoKPD3cSYz/va5PXm4um77oi75RSVp/OQ+FQoEG4GCsTbWqPuTk5Eh1TH788UdatGiBrq4uL168kAyV/Px8QkJC1OrzgEr1s3Xr1u8VE/FRpDLKyHxoiktRq1evnti5c6cQQpU+Z2VlJRo1aiS1P336VJiamoqYmBghhBDLly8XgIiLi1Mbs+DfMWPGiM6dOws/Pz+xcuVKUaVKFdG1a1dRtWpVYWhoKOzt7UV8fLy4fPmyMDc3F6VKlRIlS5YUJiYmYv78+cLPz08olUpRsWJF0blzZ6FUKsXcuXOFUqkUurq6wtjYWACidOnSIjIyUvTo0UMolUphbm4ubGxshIODg3BychLVqlUTJiYmoqS5hQAECg1R0tJaKDQ0hYaWUmhq6wj//mOEX69hAhBaSm2hoaEhNDU1hY6+oZhx/qEYGXpOaGrriNK2DqJMJWfhWDtA9Fy4SbQYM1NUb99LVPatpZq7pbXwat5BzApPEFU+6SS09Q2EhZ2TsLBzEp5N24kS5mWErqGRAIS+vr5wcHAQ9vb2wsHBQVSuXFl4eHgIV1dXAYgqVaoIDw8PUbFiRQEIOzs74eHhISwtLYW3t7f0vvj6+gojI6Mi6YWPHz8WSqVSdOvWTQghRGxsrDAxMRF37twRK1asEMOHDxeurq7C19dXOmbQoEFi1qxZ0vaSJUtEly5d1MZdtWqVaNmypdq+Zs2aiQ0bNkjb3377rWjRooW0vXnzZtGhQ4c3fST/VRSkB7q7uws7OzvxySefiFOnTqn1qVu3rrCzsxP5+flq+/ktTc/d3V24urqKLVu2vPV8ixYtkt63ny7GiIreNYWOYQlh6eAipcZ/HZ4gxuy5JLxr1hFGRkbCw8NDmuvly5dFXFycqFevnjAyMhIWFhZi6NCh0vixsbFCQ0NDlCxZUjg6OopevXoJV1dXUaZMGaFQKISxsbEwNjYWlStXFq1atRIvXrwQQgiRkZEhqlSpIl6+fCku334gTMqWF19deCxmhSeIDjN+EIAoY+8ipftWbx8kpfCfPn1auLm5CXt7e1GvXj1x9+5dtf3u7u7C2dlZdO3aVSQm/p4CmZeXJ6ysrMSRI0fe6z2TjQMZGfF24yAnJ0eULFlS7N69W61PaGiocHJyEu7u7mLMmDHCzMysWOPAwcFBuLm5CW1tbWFgYCCcnZ1FmzZtRJ8+fURubq548OCB8PHxEYaGhsLDw0PUrVtXDB06VDx+/Fi0bt1auLi4CEdHR7F06VKRn58vBgwYIEqWLCkuX74sjh49KjQ1NcXZs2dFs2bNRKlSpYRSqRQxMTGiQoUKokOHDqJ///6iWrVqwsrKSpiYmIjWrVuLq/cTRPtpS4SVs5co6+QmDExKCSPzMmLYtjAxKzxBdJr5owBElzkrxbZbL0WjVu0EIGZeeipmhSeIT78JFtZuPqKMvYswKGkmzKwriilhcaJEKQvRsVsPkZ2XL2aHJ4iJR2+IWeEJosnQSUJLW0dMPXVHzDj/SDjU8heGZqVFiVKlBSCUSqXo1KmTyM3NFTVr1hQbN24UQgjx1VdfCUD6gZ02bZpo06ZNsT+UR48eVRk0WlpSrnqrVq2k96tNmzbCzMxMutFs2LBB3L59W/j4+IiEhARRsmRJqaaBEEI0b95cmocQQuzdu1fUqVNH7TNQnHEwadIk0apVK5GZmSlSUlJEnTp1hJubm9R+584dYWZm9m4fzn8Br36/tm/fLoyNjcXZs2eFEELcuHFDWFpaCmdnZ3H06FG1Ywu/9xcuXBB6enpvrDeTnp4uKlasKFJTU8XdlGwx8egN0T/4J9Hjuw1qxsGs3z6b/YN/Equ3hkrGQQGJiYni5MmTYs+ePUXali1bJurXry+ysrJEfn6+6NOnj/jmm2+EEKraGJUrVxbJyclCCCGmT58uBg0aJB07f/58MXHiRCGEEO2D+olPv14hvn6lpk/BdnhC+rte4j8deVlB5h+NjY0Njo6Okju6IBOmZ8+eUsT6m4iIiGDz5s1qgWaenp6kpKSolbeNiIjA3NycZs2aqR3fsmVLYmJiiIyM5Ouvv5bEpEA9eC0kJISoqCjS0tLo2LEjTZo0QVNTUxKaCgwMJDMzU6q3UJCyVFDXICoqinbt2rF06VLc3d3Zu3cvjRs3lsavVKkS1apVY8+ePaxYsYIqVarg5OREfHw8gYGBPH78mLNnz1KjRg2MjY25ffs2XZoFcHnT9+RkZzJ04xGqtw/CNeATLGxV5azLu/ugpaOLS4Pm3HieSfVhs0ChwOzuJUAllJafm4PIz0PHsAT6xiZo6xnQf9gojv9ygJEjR3Lt2M9o66myPO5duUR5j6pcD/sFTS0tfFt3w8LOifEHr1GlRUe+nDyVatWqkZCQgK+vL7du3QJU8QcODg74+fnh6enJpk2byMjIICoqihs3bnDs2DGpeqGlpSV79+4lPz9fUs/s06cP3t7e6Ojo8ODBA7p27UpkZCRXrlyhc+fO9OrVi2nTpmFra4uOjo5adkRsbCzDhg0rEm+wefNmqcrnhAkTighzlSlThqNHj0qxHj4+PmhpaUnxBv91Ebc2bdowYMAA5s6dC6jc3l27dqVPnz4EBwe/9jgfHx8MDQ3fWEtk27Zt1KpVCwMDAy48zcDQ2AQbr+po6xkU6atvbIKtV3XuZhdN3DM1NaV27dpFov4BIiMjCQgIQFtbG4VCQdOmTSWl2MjISGrXrk2JEiUACAwMVFOR7dSpE8uXL0cIwQ9zZlLNVBN7Y20pY+djSeH/RxsHH1stapkPQ3EFS96VAuPg1X0FX2xQpd+2adOGxYsX/9+6GoXFpsR7CE1t3LiRI0eOcPz4ca5cucKoUaPUbizvIyo1ZswY6Zyx0Ve5eDkSe+PixcS0lKofP4WmJhpaWiAEJ3/awY/tqvPzd1PJycpEQ1MTkZ9HfkYaP/ZqTmVLU65du0ZVX1+uHdnDkq6NpFgFl/rNyC0QmXol5sJAX5cFCxbw+PHjInNetGiRNOfo6OjXlq52dHSkVKlSaGho4ObmBoC9vT0rV64sNoI7OTmZqKgo2rZtS3Z2Ns+fP+fgwYP4+/tz4sQJnj59yuDBg6V4gz179lC+fHmsra3Zv38/V69eZcKECZJWAqiCv6ZPn86vv/5KZmYmVatW5datW7i4uEjxBgcOHPjPi7hVq1aNa9eukZeXx5o1a+jVqxfdunXjp59+eq1+yaFDh8jKysLe3v614x47doxq1aqpKf6+iXzgXlou73MX8fb2Zvfu3SQnJ5OTk8OWLVskg8Xb25tDhw7x+PFj9u7dS5MmTUhJScHNzQ1PT0+aNGlCXl4e165dw8zMjCF9etLa1ogRHmZ87mrKCA8zWtsafdCif/AB6hz8GdxLzeHC0wxik7IR/G5p+ZbW++AXVObjY8qUKbx8+VLyJCxevJiLFy/yzTffMGnSJJKSkvD09KR69eosXboUhULBixcvKFmyJDExMdy7d4+SJUsyatQoBg0axIABA5g3bx6bNm0iJycHpVLJwoULqVGjBvn5+QwZMoTDhw+jra2NlpaWFKW+bt065syZw6NHj9DU1KRu3bosXbqU7OxsQkNDMTMz49KlS5QsWZLGjRuTlJSEjY0Nz58/x8TEhJcvX9K8eXM6dOjA0KFDsbW1Zffu3axduxZQ1TeoXLkycXFxPHjwgDlz5kg3xCNHjjB27FjCw8M5fPgwtWvXJigoiIyMDDIzM+nevTvlzIy59ugey/q2pEylyty+dJqstBT2zptE4PCp0vUsV9WPeZ8059POnTEgF11NTe4lv0ChIbAtX5aBn31O33790Tc2ITMthdysTDaM7oV9DT+u/LIbh1oNWNi5AY9jr2FoVpp7kRd4cTuGSYd/Ij09nWbNmpGTk0ObNm3IyclBT0+PDh06SCmckydPpn379ri4uJCenk7v3r25cOECGhoazJw5k59//hlbW1vGjBnD5cuX0dHRQalU4uTkpPaZWLJkCeXKlUNfXx9zc3PGjRvHwoULpVzxkJAQ2rVrR0hICCNHjqRbt25MmzaNNWvWUKtWLWksfX19SpQoId0ctm3bRpMmTTAyMkKhUNCqVSsGDRokiWt17tyZ77777j8v4lbwvdi3bx82NjbS+xMQEMDGjRsZOPD3CpsF0ucmJibs2rVLUs8tjvv379OkSRM1xd93m8+79+3Zsyd37tyhXr16khbIwYMHAVVlz1GjRtG8eXM0NTUZMWIEX3zxBadOncLIyAiAmjVrcv/+fTUBLaXGx1XX552Ng9zcXL766is2bdqElpYWWlpa+Pr60qtXLzp06EBUVJQUCdm+fXucnZ2ZOnUqt27dYuzYsVy6dAlTU1M0NTXp168fffr0KfKjXUB+fj6jRo1i//79aGlpYWZmxvLly6lUqRLhCRkcvJ+GBlIxNwRwMymbXT/tIe3yEbatXsGVK1cYPHgwT58+lea6ZMkSqbDFunXrmDt3Lnl5eVhYWLBq1SrKly9PYmKipM8OqqIrt2/f5unTp5iamnL+/HmGDBlCVlYWmZmZBAUFMWbMGABGjRpFlSpV3itdROb/59WCJYXzkt9E6dKlmTZtGqGhocWWSc7NzaVly5ZMnTqVzp07A0hpb926dWPEiBEAnD17lp49e/Lrr78SGRnJ4cOHuXbtGhoaGiQlJeHh4UHr1q25f/8+dnZ2+Pr64uzszL59++jZsyfffPMNDx48wM7OjoEDB5KQkMDt27f59ddfefDgAZqamkyePJmNGzdy48YNhg0bRunSpQFV1TYjIyOGDRtGbm4uly5dYs2aNcyePZtFixap3cQSExO5efMmixYtws/Pj+fPn+Ps7EyfPn0I2bKF8g078PDGVRLv3ublo/v0WrKVJd0aEnfpNJH7d1C5XmMAHqTnEmNZFR2jkjxKeIa1bSU6dg9i7fKlfLHgR0zrxrLzq1Hk5+dhZmWDZ9O2HFu9kOajv+L5/Xgu7dpIRnIS5Zw9CRw2ha1Th+DmaE+X1p8wZ84cRo0axYMHDzA0NGTOnDk0aNCA6tWrs3jxYrS1tZkzZw729va4uLgwd+5cdHR0uHnzJnFxcVSrVg0DAwM6depEbGwsly9fRk9Pj2XLltG/f3+USiXXrl1DoVDg5+fHd999R4cOHThx4oRUc8LGxobg4GDs7e3p0aMHVlZWuLm5kZ6ejr6+Ps2bNwdUypr+/v6kpKSQnJzMF198QXp6Onfv3sXAwABPT0+0tLTIy8vD0NBQWgKqUaMGQUFBjB8//n0+5v86Lly4gKurK8HBwdy4cUNajsvIyCA+Pl7NODh58uQ7R9rr6+uTmZkpKf6+6z3/fUpVKBQKpkyZwpQpUwDVMpOLi4vUPmjQIAYNGgSofh+srKwkwwD+ITLb7xqc0L17d9G8eXPx/PlzIYQQ+fn5YsuWLeLWrVti7NixUgTv+vXrhaenp8jOzhaPHj0SZcqUEcuWLZPGef78uRRFPHnyZLUI0AJ27twpfH19RXa2Kkpz+vTpon379moCTcX9WVSqLMbsCRf3UrLFjRs3RGRkpBBCiNzcXNGhQwcxefJkIYQQMTExwsLCQjx8+FAIIcS6detEYGBgsa97zpw5onnz5tK2h4eH2LVrlxBCFbBibm4url27JoQQ4smTJ8Le3l7k5ua+62WV+T8pLpBQCCF69Ogh5s+fL4Qo+jkrLJhSXDAZvwVAXb16VVhbWxd73gMHDoi6desKFxcX4eHhIQCRnp4uXr58KSpVqiR69OghVq9eLRISEkSFChWEoaGhFCUvhBC7du1SCRwNGSJWrVolGjduLLWFhoYKf39/IYQQRkZGwtjYWJQoUUKKzFcoFGLs2LFi6NChavPX0tIS2trawsPDQ7Ro0UIMHTpU9OvXT9SoUUMolUrh5OQkwsLCpHEVCoXw8PAQ3t7eYvacb4WVaxVRztlTaOvpi5Jly4sBq/aJWeEJotnI6UJbz0A06DtS6BgYCgOTUqLhoHFCz9hEjNlzSXx58Kpwa/iJKFmqtDAwNRf1ew8XJS2txcDVP0vfTUtHV9E/+CfhGtBCNBs5Q2hp6wgj8zJCS0dXAGLw4MFCCCF0dHTEvHnzpGvh6ekpNDU1pSyNggjw6dOnC1tbW6FUKqX3Uggh/P39BSB0dXWFkZGRSE1NFUKoIra1tbVF06ZNhY+PjzA3NxcmJibCy8tLnD17Vvz000+iXr160rUcMGCAcHV1fWsw4r1790SlSpXUIug/++wzMXPmTGn72rVrap+jlJQUAYh79+4V+9n6N/Lq9zQ0NFQKSDQ0NJQCDoVQvVeWlpYiIiJCCKEekPguTJo0SUyYMEEIIcT2W0lScF/fZaFFAhILgv+mbSgadFjA0aNHi7RlZGRI98KEhATh4eGhFqx85/4DkZqdJ16mpIqGDRuKhQsXSm25ubnCyMhILaPgY+SdfVpbt25l1apVmJiYACrLqX379tja2jJt2jQiIyNZtGgRI0eOZM2aNSiVSpYsWUKdOnXo27evNI6JiQkDBgx447kUCoX0ZC6EIDk5GSsrKy48zXhtkERc+Bn0DI0wK2vNhacZ2Nvb4+7uDqjWXAtrtF+9ehV3d3csLS0BVcDIzz//XKS6HRStKlW4tG1aWhra2tqYmpoCqidROzs7yb0k83FQ8PRWwP8bBJadnU2bNm2YO3cuV69e5cSJEwBkZWVhbGzM1atX+fTTT/n1119xd3cnNzcXExMT7t27J42xfv16tToHr4sRAGjbti3W1tbs27ePunXr4uLiota/AFNTU6ytrYmIiGD37t3k5eWxefNmJk+eTNmyZRkzZgxt27YlNTWV8uXLo6+vT0REBBcvXkRLU0Ep64p8tv4Xyjl74hXYju1Th6iNn5GSRFkndwKHTeHE2iWI38o1h0z6jOodeuHcsBU12gdxPzqCnMx0tHR+r3yooaHJ45sxpL98zsElX6GprcPMTXvZ8pOqlkPh96cw8fHxuLq6UqZMGW7fvk2rVq3w9/eXag9oa2tz+fJlqfaAvb092traTJo0CVdXV+Li4gBYtWoVRkZGhIWFsXbtWgYNGoS2tjaRkZH4+fnRp08fwsLC2L9/P/7+/tSoUYP09HS1wjPx8fFSsRmAhw8fFluIqUDk6XXHXb9+HQ0NDakuw3+Fjh074uHhQaVKlQgODmbfvn0cP36cRo0aqXkFNDQ06NSp0xsDE99Eu3btOHDgAABVS+uRmZHOrCbubBzTm6e3bzCriTv7F00HIDsjna+auLNgSE+io6OxsrLiiy++AFReYysrK9q3b1+kLSkpiZo1a+Li4kKdOnUYMGAALVq0kOop+PoFYOvkjJ2zG6YuVWnVs780v7CwMKpWrSrdNz5a3tWKcHd3f2P76dOnBSCmTJki7WvatKnaU8CrvM5zkJeXJ4YOHSr09fWFhYWFqFKlinielCxmv8FrEDBwnKjTbZCYFZ4gZocniOy833NlU1NThaOjo9ixY4cQQpU2Y2ZmJq5fvy6EEOK7774TgLh06ZLaPE6dOiUsLCzUZF0vX74sypcvL6ytrYWurq5Ys2aN2jFTp04VI0eOfOO1kvnzeBfPwaZNm0T16tVFbm6uSEtLE9WrV5eeNrdv364mByzE708qOTk5wtHRUe3pMSEhQSQlJQmlUikeP34shBBixowZ0jFPnz6Vngjy8/NFjRo1ROnSpcX48eOFtra2ePDggXj58qUwNTUVdnZ20tO/i4uLqFq1qvDy8hJVqlQR1apVE0IIYW5uLnR1dYWpqamoUKGCKFWqlPDz8xOTJ08WDRs2FE5OTsLS0lK4uroKExMToaGhIfLz80ViYqKwtLQUSqVS7Nu3T1hZWYnq1asLXV1dYWtrKxwcHIRSqRQ5OTli6NChqidtUzPpaV5b30BVW6B5R6FjYCgUGhqiondNYeNVXXT9do0o4+AijMtYCUMzVRqijkEJodDUEmbWFYWplY3QLWEkPt90RPp+lqvsIRxq+YsWY2YJDU0tYe/goHbtBgwYIIQQwsDAQEyfPl0IIcSKFSuEj4+P0NXVlTwrXbp0EV5eXmLWrFmif//+QkNDQ1haWgoTExPh4eEhzM3NhZWVlRg1apTkBTh06JCwtrYW3t7ewsfHRwghxKNHjyTPZFhYmDA3NxeBgYGiUqVKQgiVZ6hy5crC2dlZpKamiszMTOHt7S1++uknIYQQDx8+FE5OTmLlypVFPnu3bt0SlpaW4tGjRyI/P1+0aNFCLFq0SGo/e/bsa59SZd6N5ORkYWBgIMmXC6F6wtfV1RWenp7C0NBQVKxYUQwfPlwci30geQgqetcUXb9do7pn9BstDEqaCQcXN+Hk5CQ6dOig5hn/+uuvhaOjo3BychKOjo5izpw5ajUYXr58Kfr16ycqVqyoqiHi7im6zVv71rTEjh07isGDB0t1GArXU3jd5yI/P1/Ur1+/iBz07NmzpXog1apVE+fOnZPaXifxnJGR8U7X+E+Lhtm5cydWVlZFZG//CBcvXuTq1as8ePCAhw8f4u/vz8ABA964dpRcqE61QFW7GlRPeR07dqRRo0bSWrS9vT1Lly6le/fu+Pj4kJiYSMmSJdVSmEDlNejevbva/tmzZzNr1izu3r3LtWvXmDBhAtHR0VJ7mTJluH///v99DWT+PNq0aUPZsmWpXLkyzZs3V6se5u/vT1ZWFu7u7kU8WlpaWuzatYtVq1bh5uaGh4cH27dvx8jIiBkzZuDr64u3t7daxPm9e/do2LAh7u7uuLq64urqip6eHu3bt8fc3Bx/f3+cnZ0pWbKkJN5y5swZUlNTOXPmDOHh4dSrV4/Y2FhA5Y2oXLkyZcuW5f79+yQmJpKQ8Luk+e3bt6lcuTJXrlxBW1sbDQ0NHBwc8PX1pUGDBgghaNKkCWlpaZQrVw5HR0fWrFnDqlWrANVT7vLlyxk+fDg5mRmUtLSmRKnSeDZtB0DkgZ1UadGJEuaWZKYkkfZS5V1Lf5FIBY+qWLmorqWWtjY2Hr6M2nWe0bsvoGtYNGDs0fWr2PrUokbHXty+fbvItQMoV64c33//PZUrV2bevHmMGTOG/Px8Dh48iLa2Nhs3biQyMpKzZ8+ydOlSnJycGDVqFK6urkRERODn50ft2rW5evUqAMePH6dz585kZWURGRlJZGQkurq61KxZkxEjRpCWlkatWrXw8vJCR0dHurYFIk4dO3bEzc2NypUr07BhQyneYNKkSdy9e5fvvvtOSqMtuKa2trZMnTqVWrVqUalSJczNzenf//cnx/3799OuXbt3+OTKvI6QkBC8vb0l+fICHB0duXz5MhEREcyePZuUlBSGd2hOZ1tDtYwcBWCqq0mnTz/l+tUorl69Sk5ODjNmzABgwoQJ7N69m7CwMGJiYggLCyM0NJRJkyYBqmDKwMBAlEolN27c4NClqzT8Yh6hM0cTHfaL2lwLsiUO3Evj5rMUatSowb59+/j8888BpN+TjRs3vvb1zp8/Hzs7O7V9ERERfP/995w/f56IiAg+++wzPvvsM9U53yDxXJzXsVjeyYQQQujp6Ylnz54V2xYWFiYqVKggEhIShKenp1i/fr0QQogvv/xStG/f/rVjvs5zMHjwYPHVV19J21evXhVly5Z9o+eg1qf9RcDAcWqeg+zsbNGqVSvRp0+fIlW3CvPo0SOho6Mj0tLSpH0pKSnC0NBQqn4nhOqpUVtbW+3Ydu3aqcVUfPfdd6Jnz56vPZfMf48C78asWbPEV199JapWrSpu3Lghff7bt28vbGxshIeHh1QR0NXVVQghhLa2tli+fLkQQoiVK1eKvn37ih49ekieA2dnZ+kJ2dLSUpQsWVKqxBcUFCRKliwpDh48KE6fPi0sLCyEvr6+2LRpk3j48KHQ1tYWrVq1EqtWrZK8IZO/Wyp0SxgLzyZtBSAa9BslZoUniJKW1sKzaVvRcJDqO6bU1RPGFmWFpYOL0NY3EPolzYRDLX8xKzxBfHHgihj3c2SR76imUltMOBwjpp+5JwwNDUV6uupJqvDvQL169cSOHTuEn5+fVCCncFxFjx49hLOzs+TNmTx5svD39xd16tQRt2/fFubm5iIuLk5YWVmJGjVqCGtraxEeHi6EEKJFixYqL+Tz5+L27duiS5cuYuTIkeLGjRuidOnSYv/+/cLCwkIIoXoiK+636f8lKytLuLm5vbGIj8zbsbW1FRUrVhRGRkbCyspKeHh4CDs7O8nzU0B2drawtrYWe/bsEUIIUbdePbFp63aRnZdf5P6zZMkS0axZM5GSkiJ0dHSkWLICrl27JnR1dUVqaqr45ZdfRLly5URWVpYQ4vfYhk/GfS2s3XyKvUd9HZ4gdtxKEmvXrhVdu3Yt8pqKi20QQnX/q1Onjrh586aa5yAiIkJYWlpKHsxFixaJ1q1bCyGEOH/+vHB0dJT6JicnCx0dnXf2GgjxHp6Dtm3b0rt3b2m9XQjB9u3buXbtGj179uTHH3+kVKlSrF69mpEjR/L48WMGDRrE8ePHJYsa4OXLl/z4449vPJetrS1Hjhwh+7d86D179uDq6oq9sfZrYw7K2DvzLP6mVItakZ9Hp06dMDU1ZdmyZUXq2D969AhQrXWOHTuWwYMHS5K8oLJMPTw81NKfTExMMDAwkGqiP3v2jHPnzqmlo3xIbXeZj5vu3buzcOFCdHV11fK0xTvWOwgKClJbuwaVjnwB2trauLi4sH//furVq8eePXvYsWMHkydPpn///pQtW5axY8fy888/07hxY7p27cqhQ4eYMmWK9PSyZPqXZKelUlJP9ZSlpf37+AoNDfJzf48NqNmpL0M2H2P07gs41KhP0uMHLOhQl/Uje5Ke9LzI/JW6euRnZeFS2ohGjRqpaQucP38eKysrzpw5Q+/evTl+/Djt27fHxsaGUaNGSbUHQPU9LFjTHz16NC9evODy5cs0btyYxYsXY2NjQ+fOnYmIiCArK4ugoCA8PT05ffo0VatWxcTEhClTpnDy5El++OEHOnXqxJIlS7C0tJQiyP+qp/u4uDhmz55NqVKl/vSx/ytER0eTlZVFbGws69atk+JsVqxYUaRgkVKpxMvLi2vXrgEqj4GuVlHF34yMDEJDQ/H29iY6OhodHR1JUK0AZ2dntLW1iY6OJjw8XPJ8Fa6nUMHdh0c3rhY773zgRlI2R44epVq1au/0WnNycujbty8//vgjmpqaam0eHh4MHz6cihUrYmVlxfz581m0aBEAd+/efa3E87vyzqmMK1euZMaMGVSrVg0tLS3y8/OpW7cuR44coX79+jRu3Fia8KBBg+jfvz+7du0iLCyMcePGMW3aNEqUKIFSqVQTrgkODpYESQBGjBjB4MGDpZusUqmkTJkyLF26FGVpPW4kZRc7P6e6jTiy/Fty8/KoWlqPkJAQduzYgbu7u+RGrlWrlqSu16tXL+7cuUNWVhbNmjVj5syZauMFBwerBVKCKlBsy5YtjB49mtzcXHJychg2bBg1atQAVD/yhw8fZty4ce96WWX+Q5QtW5ZZs2apGZwArVq14ttvv6Vdu3aYmpqSk5PD1atX8fLyYujQoYSFhdG7d29SUlLYtGkTVatWZcqUKaxevVotDbMg4Hb27NksWbKE1q1bU79+fU6fPk1cXBzlypVDW1ub5ORkSpcuzcmTJ/Hx8WHr1q1kZ2czYsQITpw4Qd26dRkzZgzde2jjamPGcA8zHMKusmDKF9Kc6/caxq0LJ6neoReGpua0/vJbXj68S2k79ddWGEt7Z57euUnVOs6UGzuWadOmSRUnfX19OX36dLHHvfo6jx07Rps2bdiwYQMKhYKbN29SpkwZ9PX1adGiBaD6IW/UqJFaiurp06cZO3YsWVlZrFmzhs8++wwhhPSbUPBAEB0dTW5uLrVr137n9/ZdcXR0xNHR8U8f979EwXKvpqYmgYGB9O/fn5iYmNf2F28oYLBhwwaOHz8OQL169Rg3bhxXrlx5LwnuV+spKHVe77YXwL379wl8R1XOqVOn0qZNGypXrlykKmRcXBw7duzg5s2blC1blsWLF9OxY0fCwsLeee5v4p2NA6VSydSpU5k6depb+xasy4BqfX/79u3F9iucJ/oqy5cvL3Z/Y2sDDtxT1TkoXPnKyKQUjrX80Yo8hJVPF7p0Uf29jp9//vmNr+F1P1QBAQFcunSp2LYDBw7g6+urZrHJyBQmKCioyL4uXbqQmJgolUzOzc2lV69eeHl5MXHiRPr06YOTkxPm5ubUrl2brKysImMUpnfv3owfP15afwTVDXXevHlSJsScOXMwNjamX79+3Lp1iypVqgDg5+cnrU1qKH6TltVQULW0ek523Z5DyF0+l+97NEHxW+HXuj0/p3kNT84/zSzy/dQAXANakH01DCvDtlj5+uLk5ES5cuVISUlBCMG2bdv4/vvvpViM11Ewx9WrVwMqSe1Zs2YBv9ceSE9PJyMjAysrK8aPH8+gQYOoWbMmn3zyCV5eXmhqauLi4sLSpUulcQu8Bffu3Xurd1Pmw5CTk8O6detQKpXSGn16ejrBwcFSPMir/SMiIl6bIVewLl8YZ2dnMjMziY6OVvMeREdHk52djbOzM0lJSSxcuJCcnBy0NbWkegp3oi5S3r3qa+evAAz0Dd45Y+r48ePcvXuXxYsXk5ubS3JyMjY2Nly4cIHt27fj5uYmZb0EBQXx+eefk52dXSRj5lXl0ndBId5kVn2k3P+tQuKNQhUSHYy1qaSZTuTJQ3Tt2vWDzCskJIQ6der851KUZD4utm3bxg8//MDhw4f/1HEvP8so1jAv2G5sbYBXKT3p+/l587rk56lSMnU0NdBV5PP44QPu379fbL36D8mzZ89o0KABFy9e/E+XNP7Y2b59O3PmzJGqTYJqKdfPz4/169czevRoKSg+NTWVUaNGcf78eS5cuICmpqZkWLZq1eq1RfgAxo4dy+nTp9m5cyelSpUiMTGRVq1aUbduXb766ivy8/OpVasW3t7eLFiwgN130zlx/hLrx/Smy5yVWDq4FhlTA1Ul34g135KXlycFPxZw7Ngxhg0b9tqg/gKtloKl/R07djBx4kTOnTuHoaEhISEhTJo0ievXr5Ofn4+9vT0rVqygfv36zJ07l7Nnz6p56d/GR1M+OSdfkJ0npCeV4ti3b59aVTGBquTl2HHjaN25E2CEW4UPYxiAKo9XRuZD0qRJE27cuMHOnTv/9LG9SulhrqtVxDC3N9amaqHS5VaGSqwMlTS/ernId/rw4cPExcWpxel8DNy6dYulS5fKhsFHTnBwcBGPcOXKlSUP1PXr1/H09CQnJwchBI0bN+bw4cNF1uvfxqxZs/jmm2+oWbMmmpqa5Ofn07t3b6kcuYaGBj///DOjR4/GwcGBXKGKYxu0Zj+WDi7FjpmPqu5CpXbt6NWrl2QcpKen4+DgQFZWFklJSVhZWdGtWzfJG/Y6WrduzYULF/Dx8UFHRwcDAwPJm6KhocH69evp378/mZmZlC1bVk386Z1459BFoZJOdXBwEAqFQpKyLSA/XxX9aW9vL1xdXdVyxwtL3xZmz549wtXTS2hpa4tanftJmQbbbyVJGtbF0a5dO3H69Glpe9u2bcLV1VW4uLgIFxcXSTL3j7bt2bNHVKlSRWhraxeJWF60aJFaJoWMzH+R7Lx8kZqdp1ZPRAgh+vfvL2VdFP4ryEyQkfk3kpGRIZq26yQqVfcTM87ce6v8cmBgoDh//vwHnPHbeS/PQUBAAJ06daJXr15F2hYuXEhUlCpfVFtbm8ePH791vGwzaxqMm0fpX3aTmZ6mMlZQ6STcSMqW3JSFOX/+PM+fP5eCAC9fvsyECRM4cuQIZcuWJSUlRbIS/2hbgYrb1q1b1XJoAfr160flypUZPHjwG8U/ZGT+zbxOJKbwGr6MzH8FXV1d9m3dVOyS96ueNVDdL98URPlXkpmZ+U61Dt7LOPD19X1t25w5czhy5IjklitTpswbx7qXmsN1nbJYOpTl2hF1+dXCRSPMdbXULuqPP/6oJmz07bffMmLECGmdv7DU7h9tc3BwACjWNautrU2jRo2KqIbJyMjIyPy3KVhS+3HZcpYsWYJCAYVN6EWLFlGnTh3s7OyKFDX6u3jXIkh/SoXE5ORknjx5wq5du6hWrRrVqlWTFM5ex5t0EgpP7sLTDLV9BVrdBURHR3P37l3q1asnRXcX1Gn/o21vo0aNGn96sJeMjIyMzL+D/v36EhUZQeRvtUsK/urUqfOhp/bO/CnGQW5uLrm5uWRkZHDu3DlCQkIYPnw4kZGRxfYvXDTiTRQUjcjJ/z2h4v79+1hYWKid+/Lly+zfv5+wsDBOnz7NDz/88H+1vQ25RLKMjIyMzL+ZP8U4MDU1xdDQUEohtLGxoVatWly4cKHY/q8WjXgThXUS4Het7gLKly9P27Zt0dPTw8DAgDZt2khpLn+07W38I7S4ZWRkZGRk/iB/mvBS586d2b9fJb/6/Plzzp8/L0kmv4q2poJ3rT+l+K1/Ae7u7ly/fl3a/vTTTzl48CD5+fnk5uZy8OBBqXzxH217G3KJZBkZGRmZfzPvZRzMmDFDqn/ep08frKysJBWzWbNmsX//flxdXalbty5jx45VC2As6G9lZUXF8tbk34rg9rkTzGriTtiGH7i4awOzmrgTfXy/2uQcjLXVoqILa3UDdOrUCSsrK1xcXPD09KRs2bIMHTr0/2o7fPgwVlZWzJs3j+DgYKysrNi9e7d0TllVTUZGRkbm38wHq5B4LzWHDbFJb+3X1d5YLVshNTWVmjVrcubMmQ9SZS06Opr+/ftz8uTJv/3cMjIyMjIyfwd/2rLC+2JtqKSxtUGxkyjYbmxtoGYYABgaGjJ//nzi4uL++kkWg1x3XUZGRkbm384H11YormjEkTljuH/1UpEiK2fOnJEDAWVkZGRkZP5iPrhxUMC7aCvIyMjIyMj8W/iY73sfjXEgIyMjIyPzX+Debx7z2FfKLPu+Umb5Q/LBYg5kZGRkZGT+THbs2IG3tzeenp44OTnRoEED8vPz8fPzIzQ0tNhjDh06JJU09vHxwd/fXwo4DwoKwsHBAQ8PjyK1e8aPH4+TkxMeHh74+PioZdEV0KNHD4yMjEhLS5P2hSdk4O5gR/8GVfiukx8LO/kReWAnN5OyWR+bxOVnGUXGAZXqY/Xq1cnPV5UPbNSoEe7u7nh6elKnTh0uX75c5JhVq1ahUCjUXvv58+ffeh3hI5JslpGRkZGR+aM8evSIfv36cenSJSpUqABAeHg4CsXr3fWHDh2iW7dubN++nZo1awIQGxsrVfdt3bo1y5cvR0tLiz179tC+fXvi4+MBqFOnDhMnTkRPT4/IyEjq1q3Lw4cPpSy65ORkfvrpJzw8PNi6dSs9e/bkXmoOB++rDIXOs5dT1tFNmsubNIUApk+fzuDBg9HQUD3Tb9myhZIlSwIqHaCePXuqVSWOj49n+fLlVK9eXW2cfv36ERER8dbr+Y/2HOTkC9Jy8tXKK8vIyMjI/Pd48uQJmpqamJqaSvuqVKnyRuNg6tSpTJw4UTIMQKXKW1DH5pNPPkFLS/UMXb16dR48eEBubi4ATZs2lQLk3dzcEEJIdX8ANm3aREBAACNGjCA4OBj445pCmZmZhISE0LZtW2lfgWEAkJSUpPY68/Pz6dOnD4sWLUJHR0dtrDddj1fn8d54enri6emJs7Mzmpqa0nbHjh2Jj49Xm3RhbGxscHR0xNPTE0dHR2bPnl1sv549e6JQKHj58mWx7fdSc9hxO5l5kYmM33ECt3qN2HE7mRtPXlKtWjU8PDzw8PCgSZMmkpX38OFDGjdujKOjI+7u7rRt21btjSw8N09PTzXhqP379+Pj44O7uzvVq1dXs87at2/P6dOn3+8CysjIyMj8qbi7u1O7dm0qVKhA69atmTNnDg8ePHjjMZcuXaJGjRrvNP53331HYGCgZCwUZtWqVdja2koeC4Dg4GB69epF8+bNiY2N5WrMr2qaQlsnfsaCDnXZPnUoqS+eSccVpyl04cIFKlasiL6+vtp5u3fvjrW1NRMnTmTdunXS/nnz5lGrVi28vb2Lnes7If4P4uLihLGx8Vv3FVChQgVx+fJlIYQQ9+/fF0ZGRuLcuXNqfbZv3y769OkjAPHixYsiY1x6mi5mhSeIr8MTxKzwBOFQy1/0W7FbfB2eIL66+EScjHsi9Z03b5745JNPhBBCPH78WJw8eVJqGzVqlOjRo0excyvM8+fPhampqbh69aoQQogTJ04IFxcXqf3y5cuiTp06xb5eGRkZGZm/l5iYGLF06VLRsmVLYWxsLGJjY0W9evXEzp07i/TV09MT4eHhbx1z3bp1wsHBQTx+/LhI26FDh4S1tbX49ddfpX1RUVHCyspK5OXlCSGEGDlypBg+crSY9dt9a+zey2JWeIKYce6hqNvjc+FQy19qK/hLzc6Txtu4caMIDAx87fxWr14tmjZtKoQQ4sqVK6J69eoiOztbCCGKvPaOHTu+9fUKIcQHW1YoV64cTk5O3LlzR9r35MkTZs6cybx584o9pvB6TT7w8tF9nt66TsUqNcgHNDQ0CHuhwf3UHIQQJCcnSy4UCwsLateuLY1VrVo1yavwJm7duoWZmRkuLi6Aap3p7t27hIeHAyovSkJCAjExMX/gKsjIyMjI/Jk4OTnRv39/QkNDqV69ulrp+1fx9vbmzJkzbxwvJCSEqVOn8ssvv6gpAgMcP36coKAgfvrpJxwdHaX9wcHBpKSkYGtri42NDZs2bWLThnXk/7YkUdLSCgBNpZJan/Yj/rK66N+rmkKvCg6+So8ePTh69CiJiYmcPHmS+Ph47O3tsbGx4ezZs/Tr148ffviBZ8+esXPnzje+3gI+mHHw66+/kpiYiJ+fn7Svb9++fPPNN5QoUaLYY15dr7l96TRWLp5qfTSAZo0bUqZMGbZu3cqSJUuKjJOXl8fixYtp2bKl2v7u3bvj5uZG7969pSUHe3t7EhMTpaWD3bt3k5KSomZY1KhRg8OHD7/za5eRkZGR+XN58OABp06dkrZfvHhBXFwcdnZ2rz1m4sSJzJgxQ02R99atW2zbtg1QBf19+eWXHDp0iPLly6sde+LECbp168auXbvUhPiys7NZv349Z8+eJT4+nvj4eB48eED58uVJDj9KbkYaGSm/SwdEHtipFphYnKbQq4KDL1++5OHDh9J2aGgoZmZmmJqaMnDgQB49eiSdu3r16ixbtoyBAwdiYmLyzrIDf3u2QseOHdHQ0OD69evMnz8fc3NzAFasWEH58uVp0KBBscfl5AspJ7SA5KcPMTQ1V+uXD3y6eBvD3Ez4ZtZMvvrqK77//nupXQjBoEGDMDExkYSWQPVGly9fnpycHL788kt69OjBvn37MDY2Ztu2bXzxxRekpqZSo0YNnJ2d1dadypQpw/379///iyMjIyMj84fIzc1l2rRpxMXFoa+vT25uLj169KBly5bMnz+fPn368Nlnn0n9t27dSqNGjVi1ahWjRo3i8ePH6OnpUbp0aaZOnQpAly5dKFOmjNqD5OHDhzEzM6N3795kZWURFBQkta1bt46YmBgqVKiAk5OT2vy6dOnCT7s24FXWnvWjgxB5+QgEpuUq0GH67w+x+UDV0uqVgCtWrIiFhQXXrl3DxcWFpKQk2rdvT0ZGBhoaGpibm7Nnz563BhtqamqyZcuWd7qe/1cRpPj4eDw9PdUCB4vbV4CNjQ2hoaF4enpy6NAhWrRowfnz53Fzc6NLly6cOHECTU1NAO7cuYO1tTW7du3Cy8uLtJx8Fl19rjbeqY0/8jg2mraTvytyrs9dTUlJfIq9vT0pKSm/7//8c27dukVoaCja2trFvq5Hjx7h4OCgdlwBWVlZlClThgsXLlCpUiUARowYgbGxMZMnT37rNZORkZGR+e9y+VkGB+6locHv6YuAtN3Y2gCvUkVlArZu3cqxY8eK9Yb/FXywZYWAgAAGDhzIl19+CcCGDRu4d++e5AoBiIqKwsvLC1Ctv7xqE5WxdyHhzk1pO+XZEzKSX0rrNSEhIbi7u0vtQ4YM4ebNm+zcuVPNMEhLS1MzZjZt2iSdF1TGQgHTp0+nQYMGkmEAEBMTo+ZWkpGRkZGRKQ6vUnp0tTfG3lhbuqcVVEjsam9crGEAqsy4ypUrS0WQ/mr+kmWF5ORkrKyspG1ra+tigz4mTpxIpUqVuHTpUrEpF4VRaiiwN9bmZqFUEBvPaiQ9eUR60gv0jU14+fgBoV+NRIlgvVKBnZ0d69evB+DUqVMsWrQIJycnqlWrBqhcNTt37uTJkye0bduWvLw8hBDY2tqydu1a6dyTJk3i5MmT5ObmUqNGDSlnFVSGxZUrVwgICPijl0tGRkZG5j+ElaESK0OlmrbCi2cJNKpdt0jfhg0bMmfOHAC1ZZG/mn+UtsK91Bw2xCap7TuxZjEAdXv8ftG62hv/bfWply5dyv3795kxY8bfcj4ZGRkZGZm/mn9UhURrQyWNrVWRlgUTr/lpP7T1DaTtxtYGf6twhYaGBl988cXfdj4ZGRkZGZm/mo/ecxAREUHPnj3V9uXkC6p90gnHtn0lRSsHY22qfkSKVjIyMjIy/x4+Znnlv4KP3jh4E/+1N0tGRkZG5u/lnyCv/Ffwj1pWeBWlhgIDpYZsGMjIyMj8S7CxsSmiGlgguTxlyhTMzc0lDRxPT0+++uorALW2ypUr88knn/DkyRNpjFu3btGuXTsqVqyIt7c3vr6+rFixAoCFCxfi6uqKm5sb7u7uUiB7eEIGG2KTuFmoxo4ASV65++BhbN68GVDpH9SsWRN9fX1atWqlNv+vvvpKbc5GRkaMGDECUGkdFG4rVaoUbdq0AeDAgQNqbWXLlqVKlSqASozJ29ubpCT1OLw/i3+0cSAjIyMj89+iS5cuRERESH8TJkwo0nbt2jV0dXWlYkaPHz+mdu3aNG7cmLi4OC5dusSBAwckhUUXFxdOnTrFlStX2Lt3L8OGDeNk1K9q5foLkw8kPX3EgZ9/plYz1Y3c0tKSBQsWMH/+/CJznjBhgjTfc+fOoVQq6dKlCwBBQUFqr6dMmTJSW+PGjdXaqlSpIrXp6urSrVs3vv322z/t2hZGNg5kZGRkZP5VaGhoUL9+fUm7Z8mSJdSpU4e+fftKfUxMTBgwYAAA/v7+GBsbA6rU+zJlynD06q033iAv7tqIq39zLiaoNA+srKzw9fUtIpH8KqGhoVhbWxebvn/u3DmePn3KJ598UqTt4cOHHD58mG7dukn7OnXqxPLly/krogP+9vLJMjIyMjIyb6Jjx47o6f1eDOjmzd+L3W3YsIFjx45J21988QUdO3ZUOz4rK4s9e/ZI+y9dukTDhg3f6dyHDh3ixYsXKGxci3gMChN38RS1ugyQ5JXfdXk7ODiY3r17v7atW7duKJVFYxlWr15NYGAgpUuXlvaVKVMGPT09rl27hqur6zud/12RjQMZGRkZmY+KkJAQPD09pe3CAn1dunRhwYIFxR5XYDjcunULNzc3OnTo8F7nvXLlCkFBQazesIlLem8WKEp6+hBDM3MEkJ33bsbBnTt3CAsLk+IUCpOWlsbmzZvVRKAKEEKwcuVKFi5cWKStQNvnzzYO5GUFGRkZGZl/BQUxB3fu3CErK0vSu3kXaebo6GiaN2/OypUr8atbp0i5/ldR6uqRm5VZRF75TaxatYqWLVtiampapG3r1q24uLjg7OxcpO348eNkZmbSuHHjIm2ZmZlqXpY/i3+dcZCTL0jLyScn/x+boSkjIyMj839gamrKihUrWLJkCY8ePWLQoEEcP36cVatWSX1evnzJjz/+CKj0cQIDA1m2bBkNGzaUyvW/6QZZxt6ZxDs3i8grv478/HxWrVr1xiWFN7X17NlTEiYsIC8vT/KS/Nn8X8aBjY0NAQEBUpqFtrY2jo6O0nZKSgo5OTlMnToVJycnXFxc8PLyolWrVkVSVVatWoVCoeDkyZNq+3v27IlCoeDy5cvSvpSUFAwNDdXcTvdSc9hxO5l5kYksuvqceZGJ7LidzMEzF2nWrJnUT6FQ4ObmJs2x8PnOnTuHh4cHDg4ONGjQgAcPHgCqQJDGjRvj6OiIu7s7bdu2JSEhAVBZba1atcLBwQEPDw8aNmyotj7Wvn17Tp8+/f9cZhkZGRmZ39iwYYNaet/w4cOL7efl5UX79u2ZOXMmlpaWhIWFsWfPHipWrIi7uzv+/v7S2v6QIUNISkpi7Nix0rjpUSffGHPg5v8J188cleSVr1+/jpWVFSNGjODAgQNYWVnx/fffS/0PHTqEhoYG/v7+Rca6fv06ERERRWInAJKSktixYwe9evUq0hYWFkbVqlWL9UT8v/xfRZAKSzAXtw3QtWtXUlNTWbVqFSYmJoDqIiUmJqpdiNq1a6Orq4uVlRWrV6+W9vfs2ZOrV69So0YNFi1aBMCKFSv48ccfycnJISIigvCEDA7eL14CM/jzTowZO47eLVTCSAqFghcvXlCyZEm115Kfn4+DgwPLly+nfv36zJ07l3PnzrF161aePHlCbGwstWvXBmD06NEkJCSwevVqMjMzOXLkCE2bNkWhULB48WK2bdsmBcxEREQwZMgQTpw48Ucvs4yMjIzMB+BN8sq5+fms792Eg3t2qwkN/p106tSJ3r17v3Ow5fvwly4rxMbGsnPnTlauXCkZBqCSay5sGFy/fp24uDjWrl1LaGgoycnJauO0adOGPXv2kJWVBai8DAVW1L3UnNfmoj5/dJ+nt66TYOXJ/dScN8710qVLaGlpUb9+fQD69+/PTz/9RGZmJhYWFpJhAFCtWjVJVlpXV5fAwEAUCpVbqXr16lIbgKenJwkJCcTExLzlasnIyMjIfEy8SV65u6MJ64KXq/3e/51kZmZSr169v8QwgL84W+Hy5ctUqlTprS6PgvSNsmXL0qBBAzZv3ky/fv2kdn19fRo2bEhoaCgeHh4IIahcuTIAF55mFLHqCrh96TRWLp5o/NavoNSlv78/ubm5+Pv7M336dAwMDLh79y4VKlSQji1RogRGRkY8fPgQW1tbaX9eXh6LFy+mZcuWxb6W7777rkhbjRo1OHz4sDRnGRkZGZmPn2nTprFjxw5AVRlRCFAoYMf27VgZ2mFVTK2CvwtdXV0GDhz4l43/twYk3rp1C09PTxwdHQkKCgIgNzeXtWvXStu9evUiODi4yLEF+4ODg6W+AohNyn7tulDy04cYmpqTD1Iu6p07d7h06RKnT58mISGB0aNHv/P8hRAMGjQIExMTBn0+pEjg48yZM7l58yazZs1SO64g1URGRkZG5p/DpEmTpOqEkRERREWq/rWzs/vQU/vL+Us9B15eXty8eZMXL15gYmKCnZ0dERERrF69mtDQUAD27NnDy5cvpRQNIQQPHz7k6tWranmb1atX5+HDh8TExBAdHc2lS5cQAt4UMKHU1SM3W7UUUZCLWr58eQAMDAwYNGiQ5KEoX768VE0LVEGPSUlJlC1bVto3ZMgQYuPv0v+7dSy48kJNhCN80w/s37mDQ4cOoa+vrzaPzMxMqfqWjIyMjIzMx85f6jmwt7enZcuW9O7dm5cvX0r709LSpP8HBwezYMEC4uPjiY+P586dO4wYMaJY70FCQgJ5eXnUqVOHbt26kZDwFAXw4uFdptb93ZL7ulkVvm1dndObVxC5fwdnQoJRADFXo6SbdH5+PitWrODu3bvMmzcPFxcX7t27h5WVFR4eHnh7e1O/fn10dXUBlWEQHn2dBtNWcCfjd6MkKyOdoBqVWbl2Pd9u3i0FOh45cgRNTU0WLFhATEwMHh4etG7dWi3KVkNDg927dwOq8p4FWRSurq5qxS727t2Lt7c3Ojo6DBs2TO2aLF68mJkzZ/6xN0hGRkZG5k/j35RK/5dXSFy9ejVfffUV1apVQ0tLCxMTE8zNzRk7dqxUK7pwdgKoCln4+/vz9ddfq+3X09OTsiG2bt1Kp06dIP4KCu2iT+WdZy/HwtaJb1p4s3/xDPzq1uFu5mNSU1Px8PAgLS2Nx48fM2vWLD7//HMyMzOZNm0aa9asISMjAyGEZNCcOnWKRYsWYW5jT1x3lYfDpFwFun27hqMr5pP89CFa2tp0btYIEx1N9LSVaGhoEBgYSFZWFleuXCEgIEBNqevixYs0adKEJk2aAKqsjsGDBwOQnJyMq6srderUwcvLC3t7e1auXMnWrVtJTU1Ve539+vWjcuXKDB48WPZOyMjIyHwA/o2yzv+XcfBqlGZxUZva2tpMnTpVUsd6lfT09CL73N3dpToCrxoOBbRv3565c+dilPqY56bF3xQ1lUpqde7H6c3L0X9+lyq1q1OiRAlWrlxJq1atWL9+vXTD1tXVZeTIkYwcORJQ3bzbtWsHQK1atdh+SyXb+Wp8Q9QvoYzadR4z64pooPpA7Jg8mPbt27Njxw4uXrxIz549MTQ0VDsuODiYrl27oq2tDaB2Y09LSyMn5/fsCgcHBwB27txZ5DVqa2vTqFEjNm7c+JcGp8jIyMh8DNjY2JCens6DBw+kOgVHjx6lQYMGVKxYESMjI0ClxJiXl0e5cuUAVQp6bGwsL1++VCu/XLDMHRoaSnx8PHZ2dmpFhQYMGMCAAQPw8/Pjzp07GBsbk5GRQWBgIN9++y0RiVlSKv2rss43krKpmHSLtXOmsXfvXgBevHjBZ599xoULF1AqlbRo0YLZs2cD0K5dO06fPs2jR4/UUu6vXLmiJrj08uVLkpOTef78uXRNdHR0pEqJhfUm6tSpw9q1a6lYseJ7Xed/rLbCr7/+SmJiIu2aBHD+XiILodhcVDvfOhxeOpsG1VRRpenp6TRo0IAtW7YUW4qygMJZBzn5QrIIC/Py8QMyU5Mxs1Zd9Hxg+/ZtKBQafPLJJ+zYsQOFQsEXX3yhdlxGRgabNm0qUvBp27ZtTJ48mZs3bzJz5ky8vLze6VrUqFGD3bt3y8aBjIzMf4Ly5cuze/du2rZtC6getnx8fKhVq5Z0458yZUoRQ2DKlClvHbtEiRJFivQVMH/+fFq1akVycjKenp7Ye1Ul2a0RULysM8CkLycwc+LvstK9evWiVq1abNiwAVAZMQUMGDCA77//HgsLC7Wx3Nzc1Ob02WefSenzBbyqR1HAyJEjmTx5MmvXrn39iy6Gf5xx0LFjRzQ0NLh+/Trz58/nwYMHjO76KdnpqfzQpQFZefkkJzxm5aD2mJcpi1kJAzasX4+9vT3x8fHo6uri7+/PkiVLqF+/vvTkXpiCrIPDhw8DqkDG4laQkp6osiEKSHn2hCMr5nEh7PeCRzVr1sTAQF3AY9u2bTg4OBQpedmuXTvatWtHfHw8rVu3pnnz5jg6Or71msjZEDIyMv8lgoKCWLlyJW3btiUpKYmzZ8/SuXNnUlJS/pbzGxkZUbVqVc5G38LVrfhUeoCXv9Xa0bBXPZzevHmTixcvsn37dqlPmTJlpP8HBAS89dyZmZls2LCBo0ePvtNcmzVrRt++fUlKSnqvped/nLZCSEgIMTExHDx4kHHjxqGpqcm+ffsoUaIEcdFR3Im5glW5shw99Atx0VFcPHdGWh4Alc53SEgISqWSNm3aSIWVCpg7dy47duzg559/lrIOtDUVxYpwaOv9ng0B8CAmkpRnT6lVtQo2NjZs27aNadOmMWHCBLXj3lRDG1QuomrVqrFnz553uiZ/lfCGjIyMzMdIrVq1iI+P5+HDh2zatIn27dsX0R14Ha+WX540aZJae0pKilr7vXv3iozx6NEjIiIjMa/q/8YSywW1dgpS6aOjo7GysmLgwIF4e3vTqFEjNWmAd2HHjh3Y2toW8RJ0794dNzc3evfuLS3LAyiVStzc3Ip4qt/GP844KCAgIICBAwfy5Zdfqu1Xaqhu5G8SwlAqlYSEhKCnp0erVq3IzMwEYN68eWzatIlffvlFrbzy60Q4SlWoROrzBHIyMwBwrtOItRduSpkX7dq1Y9KkSXz11VfSMQWWY+fOndXGio6Olv6fkJDAkSNHcHd3f6drUZANISMjI/NfoVu3bqxevZqVK1cWqzvwOgqUGwv+pk2bptZesKxQ8GdtbS21DR8+HFdXV8qXL0/Dxk0wt3V447kKau0UpNLn5uZy/vx5OnXqxKVLlxg+fDjNmzdXizF7G8U9XJ44cYKoqCjCw8MpVaoUPXr0UGv/I97lf6xxADBx4kTCwsJITEx872O1tLTYtGkTRkZGtGzZkvv37zNy5EhevnxJ/fr18fT0pFq1alL/qqX1iliISh1d7Kv7ceuCyiLL/63fmyhwhRUEzRTw3Xff4ezsjKenJwEBAQwbNkwqi3n48GGsrKyYN28ewcHBWFlZSSmQAPv371fzjsjIyMj82+nevTsLFy5EV1cXe3v7v+Wc8+fP5+rVq1y6dIl1q1dx49ShN/YvqLVTIOtcvnx5ypUrJ5Xpb9q0KdnZ2Wo1dt5EXFwcZ8+e5dNPP1XbX1C/R6lUMmzYsCJegj/iXf5HxRy8mg1hYmIiGQaF6yi8rta1jY2NWj8tLS1CQkKk7TdpUFkbKmlsbVBEhKNezyEcWTYXpzqNaGxtoJa2UlymxetqEhRIhxaHv7//a62+6OhocnNz1bQfZGRkZP7tlC1bllmzZuHk5PS3n9vd3Z3p06ez4IeZONb0RyiK91SXsXfh6qHdkqyzt7c3RkZGREVF4e7uzvnz5xFCqHkn3sTKlStp3bq1mme7ILutYN+mTZuKBLPHxMQUWT55G/8o4+BD41VKD3NdLS48zeDGb9kL5V2r4N+8Ja3KaOBU6u9f9793794bDQsZGRmZfysFpfQ/BAMHDmTBwkVcObIHV/8Wxfax8azGyyePqKSVARihUChYs2YNffv2JSMjAx0dHbZv346Ojg6gCh6MjIwEwMXFBXt7e0nhNz8/n9WrVxfJOnjy5Alt27YlLy8PIQS2trZqfeLj48nLy3vvpef/S7L5v4KPjw+5ublq+yo7u7BizTq0NRVvjG+QkZGRkfn38iZZ53zg8a5llDNQvpeOz5/JuHHjqFSpEn369Hmv42TPwTtw8eLFDz0FGRkZGZmPkOI8ygUVEquW1qP0+FHFygH8XZQtW/a9AjYLkD0HMjIyMjIyf5CIiAh69uwJqMs69+zRg+HDh3/Quf0/yMaBjIyMjIyMjBr/6FTG1/FvUsaSkZGRkZH5u/lXxRz8G5WxZGRkZGRk/m7e2XPg6emJs7MzS5YsIT4+Xi3PsgCFQiHVERBC8M033+Dk5ETlypVxcnJi7ty5CCHIycnB09OTLVu2SMfu2bMHJycnMjIyuHLlCnXr1sXJyQlXV1d69epFRkaG2nnc3Nzw9PTEycmJzz//nAuPU9kQq1JOfFUZa31sEpefZTBq1Cg2b94MwIULF6hZsyb6+vpqUsqgUj90d3eXXvOECRPUaiDMmDEDOzs77Ozs1Eojv2nMAjIyMqRiRwVERUXRtGnTt74HMjIyMjIyfwfvbBxERETw888/M378eJKTk9/af8KECezevZuwsDBiYmIICwsjNDSUSZMmoVQqWbt2LcOHD+fJkyckJiYyYMAA1qxZg56eHrq6uixevJhff/2VyMhI0tLS+Prrr9XGP3nyJBEREURFRXH42HGWbFFVDHydMtaWSzfZvWevJGNpaWnJggULmD9/fpG5BwQEqJXP/OWXXwgNDQVUZSo3bdpEVFQU0dHRHDhwQJLifNOYBYwdO5ZatWqp7XN3d0dHR4cjR4689brKyMjIyMj81bxXzEGFChVwdHTk4MGDb+yXmprKvHnzWLZsGaVKlQKgVKlSLFu2jLlz55KWloa7uzuDBw+mX79+DBw4kG7duknliu3t7SVdAU1NTapWrfraqocZGRkkpWeib1TyjXO6tGsjHgEtJJlLKysrfH19peIThSlRogQaGqpLk5mZSVZWlnRcSEgI3bp1w8DAAB0dHXr16sWmTZveOibAoUOHePDgAV26dCnS1rlzZ7mYkYyMjIzMR8F7GQdXrlzh119/pWXLlkWUqwq7yaOjo9HR0cHZ2VnteGdnZ7S1tSWRobFjx3Lz5k2ioqKYOnVqsedMS0tjxYoVtGzZUm1/nTp18PDwoGzZslhU9qK8h+8b53774ikM7D3fOUjx9OnTuLm5Ubp0aRo0aCCd/+7du1SoUEHqZ2Njw927d9863suXLxkzZgw//PBDse01atSQJKJlZGRkZD48/+Xg9ncOSPT09ERfX5+VK1eiVCol5arCKArVl1a8ptZ0Ya5evcrLly/Jzc3l8ePHknhEAdnZ2XTs2JFGjRrRunVrtbaTJ09SsmRJEpJSqR3YktObl1OzU9/Xnivp6UMMzMzJzhPvVNGwZs2aXLlyhYSEBNq2bcvJkyepW7fuW497HZ999hnjx4+ndOnSagqMBZQpU4bExEQyMzPR1dX9w+eRkZGRkfn/kIPb3zPm4PTp0++k/ufs7ExmZmaRm2B0dDTZ2dk4OzuTnZ0tqWqNGjWqSGnHnJwcOnbsiKWlJd99991rz1WyhAGV6zbmxuk3r9crdfXIy8pEW/P9Sh2bm5sTGBjI1q1bAZX6VWEFrfj4+CJGTXGEhYUxatQobGxs6NSpE9HR0Tg6OkrtmZmZaGpqoq2t/V7zk5GRkfknU+B5dnZ2RlNTU9ouiA978uQJvXr1wtbWFg8PD9zd3RkwYIAkujdlyhTMzc3VvNgPHz4kPj5ebTwnJydmzJghnXfv3r14e3ujo6PDsGHDpP3hCRlvDG5v+Ekbzpw5A8DChQtxdXXFzc0Nd3d31q9fL42TkZFB9+7dcXV1xdXVlU8++YSEhARApZMwYsQInJ2dcXd3p379+ty8eVM6ds6cObi6uuLs7Ezr1q2lQP/MzEy8vb1JSkr6k9+FovwldQ4MDQ0ZOnQo/fv359mzZwAkJibSv39/RowYgYGBAZMnT8bFxYW2bdsycuRIUlNTWbZsGQC5ubl06tQJU1NTli1b9kYvhIbI52nUGcwrVHrjnCztndF4Gv9OXoNff/2V/HxVKGNKSgp79+6VYiDat2/PunXrSEtLIysri5UrV9KpU6e3jhkfHy/9bd68GWdnZ65fvy61x8TE4OrqKsU6yMjIyPwXKAj83rdvn+SRjoiIICQkhPT0dOrWrYuNjQ2xsbFERkZy8eJFPDw8ePDggTRGly5d1ILIy5YtC6A23rlz51i8eDHXrl0DVLFtK1euVNM8uJeaw8H7aUDxwe33roYT9/gZ1m4+gEoc6dSpU1y5coW9e/cybNgwbt26BaiUdtPT07ly5QpXr17FwsKCOXPmALB7925OnTpFZGQkUVFR+Pv7M378eAB++eUXVq1axZkzZ4iOjsbb21vKitPV1aVbt258++23f+6bUAx/WZ2DWbNm8c0331CzZk00NTXJz8+nd+/ejB49mrNnz7Ju3TqioqIA0NDQYNWqVdStW5fGjRsTFhbGjh07cHd3l6Qna9WqxZIlS6Tx69Spg6amJtnZ2di7uOHV782iFq7+n3D3+A7gcwCuX7+Ov78/6enpZGRkYGVlxfjx4xk0aBAhISGEhISgVCrJy8ujXbt2kmfDz8+Pjh074ubmBkDHjh1p3rz5W8d8G/v3738nr4yMjIzMf4WNGzdiYmKiJjesra3NwIED33ustLQ0hBAYGRkB4ODgAKhS1wu48DSjiIBSYc5vX4Nn0zZceJqBlaESf39/qc3a2poyZcpw79497OzsUCgUpKenk5OTg4aGBqmpqdJ9Q6FQkJWVRWZmJlpaWiQnJ2NlZQVAZGQktWvXpkSJEgAEBgbi5+cn3f86deqEl5cXU6dOfafl+z/Kv6Z88tuUsRqW06N/YD1CQ0OlN+FjITs7Gx8fH44cOSJld8jIyMj8l4iPj8fT01NyoQMMGjQIpVL5xqXlKVOmsGTJEsqVKweAl5cXq1atIj4+Hjs7O9zc3MjLy+PGjRuMGTOG6dOnFzn+5cuXzJk3n3mRibzphjjnk6p0m7cWy0qVGeFhpuaJPnToED169ODGjRsYGBiQmZlJjx49OHDgAJqamlSrVo09e/agoaEhLSssX76cEiVKUK5cOY4fP46hoSFHjx6ld+/enD59GgsLC0aNGsW8efNITEzE1NQUAFtbW3bv3o2rq+v7X+h35F/jw/YqpUdXe2PsjbUpeLsKgki62hvjXdqAH3/88bUpkR+SuLg4Zs+eLRsGMjIyMm8gJCQET09PKlasyPLly6X9hZcVVq1aJe0vWFa4cuUKjx49Ys+ePezevbvYsbPzxBsNA4CkJw8xNDNH/Na/gCtXrhAUFERISAgGBgYAHDx4kPz8fB4/fsyjR48oWbKk5AG5ePEiV69e5cGDBzx8+BB/f38GDBgAQP369Rk1ahTNmzenevXqmJubA6Cl9bujv0yZMty/f/+dr9sf4V9VPnnlvFns2LFDTRlLAWzfvh0M7fD29n7vMXPyBdl5Am1NxTvFK/wRHB0d1YITZWRkZGRUXoCVK1dK2x07dqRjx4707NmTtLS09xrL1NSUhg0bcuDAAT755JMi7dqaChTwRgNBqatHblYWit/6gyrQvnnz5qxcuZLatWtLfZctW8ann34qZZ916dKFmTNnArB27VoaNGggVRru0aMHjRo1ko4dNGiQtBx99uxZrKyspOUQUAUm6unpvdfrf1/+NZ4DgEmTJhEREUFkRARRkap/IyIisLOze++x7qXmsON2MvMiE1l09TnzIhPZcTuZ+6k5f8HMZWRkZGRe5dNPP+XZs2d89dVX5OXlSfvT09Pfe6ysrCxOnTr12gcxpYYCe2PtN94ULe2dSbxzEwdjbZQaCmJiYggMDGTZsmU0bNhQra+trS0HDx5ECIEQgr1790rLALa2thw5coTs7GxAJR9QeIng0aNH0uucNGkSY8aMkdry8vK4deuWFL/wV/FRGgc2NjaSRvaCBQuk/bNmzcLFxYUHDx4QGBhYpAiTpqYms2fPBlSBgxUrVpTaAgMDgXfTPygulWXv/Mls2xLC+tgkvl2z+Y3aC1C8hkJ8fDx+fn4YGxur7S+MEELNogRVKo+vry+5ubnvcxllZGRk/tEYGBhw4sQJYmNjqVSpEl5eXtSsWZNSpUrRpk2btx7/arE+Dw8PKZjx8OHDWFlZMW/ePIKDg7GysuLFhUOvDUYEcA1owfXTR6laWvXUPmTIEJKSkhg7dqx0jgMHDgCqWIbU1FQplfHJkyd89dVXAAwePJiKFStKqZmHDx9WK5DXqFEjXFxc8PDwoHbt2nz22WdSW1hYGFWrVpXiD/4qPsqARBsbG0JDQ1mwYAGenp4MGzaM0aNHc+LECfbt24eZmVmRYxYvXsz333/PuXPnKFGiBH5+fgwbNqyIAXD//n0ePnzI5cuX+fnnnyXNhALupeawIVY9hzTp6SNWDmzHsG1hqijTtFSC3C0pb6RDdnY2tWvX5osvvlAr1DRkyBAyMjK4cOGCVCzq+fPnREdHk5SUxIQJE4oUkQKYN28eMTExbN26VS0wZ9iwYbi7u9OrV6/3upYyMjIyMu/Om4LbM9JTWd+vBRHnz0qxBX83nTp1onfv3kU8FX82H6XnoDB5eXn06dOHy5cvc/jw4WINg7CwMKZMmcLOnTul9I/X8Tb9g4JUlsJc3LURF//mUtqInoEhl55lAUW1F+D1GgqmpqbUrl37tR+qa9euERoayrhx44q0ydoLMjIyMn89bwpu7+1RjqULFxAXF/dB5paZmUm9evX+csMA/gEBibNmzcLV1ZUDBw4Ue0N/+PAhHTp0IDg4uMha0vDhw5kyZQoAffv2ZfDgwW88V06+kMplFibu4ilqdRkgbecDv5wIY2LLsdyMjWXgwIGS9kKBhsL+/fuLLZP82nPn5NC3b1+Cg4PR1NQs0u7t7U1UVBTJyclqgSkyMjIyMn8eAwYM4OzZswBqwe1nz5xBT0+JVaHaBn83urq6f6jGwx/hozcO/Pz8OHHiBGFhYWoFJ0BVH6Bt27b06dOniDATwPz5818bV1Acr0tlSXqqSl8pTHkPX86FR5L+MlFNe+FtGgqvY+rUqbRp04bKlSsXm26ppaWFiYkJDx8+lI0DGRkZmb+IpUuXfugpfBR89MsKtWvXZtu2bXTu3JlffvlFre3zzz/HzMzstYqO70tBKsurqNJXMtX2FaSyvKq98DYNhddx/PhxFi1ahI2NDbVr1yY5ORkbGxupFjf8PekrMjIyMjIyH71xAFC3bl127NhBly5dpEjQFStWcOTIEdavX/+nlZB8XSpLGXtnnt35XRTjWVwslUpoodRQFNFeeJuGwus4efIkd+7cIT4+nrCwMIyMjIiPj5cKYDx58gSFQoG1tfWf8lplZGRkZGRexz/COACVB2Hnzp1069aNn3/+mc8++4z09HT8/PzUUlUK1+AujuvXr2NlZcWIESM4cOAAVlZWfP/991J71dJ6RVJZ3Pw/4caZo9J2xMFQvmheAw8PD2rUqIG/v38RVcniSE9Px8rKivbt2xMdHY2VlRVffPHFO73+/fv307p1a1mYSUZGRkbmL+ejTGX80LyaypKfn8/33RrRfd5ajCzK0tjaAK9Sf697v06dOixbtozKlSv/reeVkZGRkfnvIRsHr+F+ag4XnmZw47fshQfRkVgqc+ke2AArQ+XfOpcnT55w+PBhPv3007/1vDIyMjIy/01k4+A3pk2bxo4dO4rs37x1G9Y2tn+ptoKMjIyMjMzHhGwcyMjIyMh8lPwdwncyxfPR1zmQkZGRkflvce+3Zd2ConQFFQp9S+v96cu6sgFSPHLou4yMjIyMRGHhO21tbW7fvi21jRo1Sqo6W8CqVatQKBScPHkSgPPnz1OmTJkiQnE7d+6UUr5BJVNsZGRURHq5OOE7AYTfvEvNGjW49FTVf//+/fj4+ODu7k716tWJjIyUxpg5cyaOjo5oaGgU0c95+vQpTZo0oWIle8o7OPPZyp+KKO8eOXIETU1NNeG/UaNGsXHjxve4kv9sZONARkZGRqZYypUrx4QJE97YJzg4GH9/f4KDgwHw9fXF3Nycn3/+WepjY2PD/Pnz0dXVZcGCBSQnJ/PTTz/h4eHB1q1bJbVcPX19unVoC6iLHh1Z8S1z29Tk+YM7jPriS67ee0qXLl1o3bo1d+7c4dmzZ1SrVo369etz48YNAgIC+Pnnn6lbty5XrlxBoVCwbt06AMaNG0cFN2/6bz1Dy0nfsXnCAPJychDAzaRsVoTfo3XbdtSoUQOAvXv34u3tzcKFCxk8eLCadPTChQtxdXXFzc0Nd3d31q9fL7WlpaURFBSEm5sbTk5OjBs3TlLvzc/PZ9SoUbi6uuLk5ETv3r0l+eaPRYVXNg5kZGRkZIqlX79+nDp1ivDw8GLbr1+/TlxcHGvXriU0NJTk5GQAevfuzcqVK6V+ubm5XLhwAVtbWwA2bdpEQEAAI0aMIDg4GEtLSxYsWECP8TOLnCPu0mki9m1HQ1OTETvPEHvmKPOWrcTMzIxy5cpRv359bt68iba2NlZWVgwbNgxfX1/pXIcOHVIzXkK2bKFUI1XmVzkXL4zMyxAXfhpQGSSbvuiHfilLLCuojre3t2flypWMGTMGY2NjDh48KM3NxcWFU6dOceXKFfbu3cuwYcO4desWoPJe5OXlERUVxZUrV4iMjGTbtm2AyqAKDw8nPDycmJgYNDQ0+O677wCwsLCgZs2arF279g+8Y38esnEgIyMjI1Msenp6TJ48mbFjxxbbHhwcTLdu3ShbtiwNGjRg8+bNAHTt2pVffvlFKv+elpZG3bp10dXVlY7r1asXzZs3JzY2lrS0NLx8qpKYV1R0LupgKBWr1MC0XAX0jUri3fJTLp49S2JiIrGxsQDs3r2blJQUKlSowJ07d6Rjc3NzuXjxIuvXryc6OpoLFy6QnZODcSkLqY9JWWteProPwJVDu0m8d5tan/YlMVPlIXBwcMDDwwMtLS0sLS05fPiwdKy/vz/GxsYAWFtbU6ZMGe7duwdAZGQkTZo0QaFQoFQqadiwoeS9iIyMJCAgAG1tbRQKBU2bNpXa4ONQ4ZWNg/+DnHxBWk4+OflywoeMjMy/k549e/LgwYMi2ja5ubmsXbuWoKAgAHr16iU9nZcqVYrAwEDphpeamiqJ4D18+JBHjx7RqFEjlEolXbt2ZeXKlWTnFf87+vLxAzSUSkn8zqSsNSmJT1i3eQvbt2/n2LFjHDx4EGdnZy5cuECnTp2kY58+fYqXlxdlypSha9eurNuwASEoUgUXIOXZE46umEdeXi5Wrt4k5eSR90oyn76+Pvfv3y92nocOHeLFixdUrVoVUCnpbt26laysLFJTUwkNDZVE9by9vdm9ezfJycnk5OSwZcsWNcG9wiq8H4qP0jjIzs5m7NixVKpUicqVK+Pm5saaNWsAlXaBpqYmnp6eeHh44OHhwd69e6VjV69ejUKhYP78+Wpj1qtXD4VCwcuXLwGV2mPFihXx9PSkUqVKNGzYUG2cY8eO4enpWWRuaWlpeFX1xaayG+Wd3PCqF8CXP1+WAlleR2RkJM2aNZO2161bh4eHB66urvj7+3P37l0AEhMT1cpBOzg4oKWlxfPnzwEQQjBlyhQcHBxwc3Ojfv360phBQUG4u7vj6elJ1apV1Szc9u3bc/r06bddehkZGRk1NDU1mTlzptqaOcCePXt4+fIljRs3xsbGhsGDBxMeHs7Vq1cB1dLCqlWrCAsLQwhBtWrVADh37hwpKSnY2tpiY2PDpk2bWLt2LRoir9jzA2gptcnNylLb19C/gTSnEydOEBMTw6+//sqgQYOkPo8ePSIgIABQGS/btm5FQ1OTlGdPpD4vHt6jpKUVD2IiSXn2lJcP77H6805cPfQTX02frhZzkZeXV6z43ZUrVwgKCiIkJAQDAwNAFdtQvnx5qlWrRrNmzfD19UVLS5Ug2LNnT5o0aUK9evWoV6+e9Dsvvd5CKrwfDPER0rlzZ9GmTRuRmpoqhBAiLi5OODk5iRUrVoi4uDhhbGws9f3pp59EiRIlRG5urhBCiFWrVgkvLy/h4eEh9YmNjRVVq1YVgHjx4oUQQoh69eqJnTt3Sn2OHj0qLCwsxPbt26XtwmMUcOFxqphyMk58HZ4gZoUniGYjpovK9ZpI2+EJ6cW+pqZNm4oTJ04IIYSIiYkRFhYW4uHDh0IIIdatWycCAwOLPW7OnDmiefPm0vaCBQtE69atRVZWlhBCiEePHkltBa9NCCHCw8OFiYmJyMvLE0IIcfnyZVGnTp1izyEjIyNTQIUKFcTly5dFjx49xPz586X9NWrUEDY2NmLy5MlCCCGaN28ufvjhB7Vjx4wZI4YNGyaEECIvL09YW1sLHx8fYWxsLC5fviy6du0qDAwMRExMjNpxvr6+IjQ0VAz++nvh7NdUzPrt93RWeIKo3j5I1Ok+WBiVthSzwhNEq3Ffi7otO4iHDx+KVatWiZYtW4oJEyaIli1biqZNm4oOHToIIVS/eYAoVaqUqFChgqhQoYLQ1tYWdlXrCP9+o8Ws8AQxaN1BYWReRsw491A6n24JYzF2X4So0qKjmDtvnjTHyZMnCzc3N7VrIoQQ165dE+XLlxcHDx5843WdNWuW6Nq1a7FtmzZtErVr11bbZ2JiIuLj49845l/JR+c5iI2NJTQ0lGXLlkkWmI2NDd9++22x0sz+/v6kpKRIT9YA5cuXx9zcnAsXLgCwcuVKyfX1Ovz8/JgyZQqzZs16bZ97qTkcepiBjoEh+aie4jPTUlAoFJKb6sC9tCIehLt373Lt2jXq1KkDwNWrV3F3d8fS0hKAwMBAfv75ZxITE4ucMzg4mN69e0vbc+bMYfbs2WhrawNQpkwZqa1kyZLS/5OSktTG8fT0JCEhgZiYmDdeBxkZGZni+PrrryXX98OHDzl8+DDt27dX69OlSxfWr19PdnY2GhoaBAUFcenSJQwNDQG4d+8eJiYmODk5FTkuODgYWyPtIud1a9iS62GHMDAx48GvUVzYtZGgLp2ZNGkSX3zxBYcOHeLOnTusXr2aFStWsG/fPgYPHkzt2rXR1NRECCEFRC5YsAAjPV3uRl1gbktftk3+nA4zfkBT+XvtBEt7ZxLv3MRYqYlmIcVfIQT37t2jdevW0r6YmBgCAwNZtmwZDRs2VJt3cnIy6enpAMTFxfHDDz8wcuRIADIzM3nx4gUAz549Y/bs2YwZM0Y69qNQ4f1gZslrCAkJEe7u7kX2P3/+XADi/Pnzap6DtWvXigYNGkjbBZbkhg0bxIABA0Rubq6ws7MTL168eKPnQAjV07aenp4QonjPwfZbSZKHwM63rjA0NRcWdk5i3P4oyer8OjxB7LiVpHbc2rVrRdu2baXtGzduCDMzM3H9+nUhhBDfffedAMSlS5fUjjt16pSwsLAQOTk5QgghkpKShJaWlvjmm2+Er6+v8PX1FZs3b1Y7ZuzYscLW1laYmJiII0eOqLUFBQWJRYsWFbm2MjIyMn8lhb0RxsbGoly5ctLfli1bxK+//irKlSsnTExMhI6urjAqbSlajfta+l0NGDBWGJqWEjoGhiJoyChp3ILf+8JMmTJFBAQECBMTExEVFaXW9uzZM6Gnry/G/3JNzTtR+K/FmJmiTrfB4l5KthBCiEOHDoly5coJPT09oaWlJcqVKyd27dolhBAiICBAlCxZUnh4eEh/+/fvF0KoPBf29vaicuXKws3NTfJKCyHE48ePhZOTk3B2dhZOTk5FPDCrV68WvXv3/tOu/x/hH1khMSUlBU9PT54/f86zZ884cuRIkT5t2rRh/Pjx7Ny5k2rVqqk9Vb8O8YZK0jn5QqrWBdBn6Xby8/M5Gjyfo8HzafXFN4Aq0OVGUjY5+UKqtnX//n0sLH6PjrW3t2fp0qV0796d3NxcmjVrRsmSJdXWnEDlNejevbu0Pzc3l9zcXDIyMjh37hzx8fHUrFkTJycnPDw8AJg9ezazZ8/m0KFDjBkzhlOnTql5GV4XTCMjIyPzV1HgcVi9evVr+xT+bXpV+C6g3ygGjR7PtZ2rGD/8c6lfz5496dmzp9o4kydPfu05zMzMSE9LK6K8W4AG4P1JZ9b3a4GJIhtQ4u/vz/379wkJCaFOnTqULVtW6v9qkGZhPD09uXHjRrFtFhYWb/TirlixgmXLlr22/e/go1tW8PLyIjY2toiL/cyZM1hbW2Nubk6JEiWIiIjgzp07jBs3jk6dOpGZmanWX1dXl6ZNmzJw4EB69er1Tue+cOECrq6uxbZl5wleNR00NDTwbd2Vy3u3qO0Xv/UvQF9fv8j82rVrx9mzZ7l48SIDBw4kIyODSpUqSe2pqals2bJFbe6mpqYYGhrStWtXQLXcUqtWLWn5pDABAQGkpKRw5coVaV9mZmaxwTQyMjIyH5qnT59KgdjNa1dlapu6bAwK4PH62YzwMKO1rRFfjhyKhsb/f9vyKqVHV3tj7I21KVg4KCjR3NujHEsXLiAuLk7tmI4dO6oZBn8VT548YeDAgVSuXPkvP9eb+Og8B/b29rRo0YJ+/fqxbt069PX1iY+PZ+TIkUycOFGtr0KhYOLEiezevZsffviB4cOHq7WPGDECOzs7GjRo8Nbznjx5kilTprB48eJi27U1FSiA5GdP0NLWQc+oJKDKwbW0d1af12/9C3B3d2fr1q1qfR49eoSlpSV5eXmMHTuWwYMHo6+vL7WHhITg4eFRZG2uc+fO7N+/n0GDBvH8+XPOnz/P6NGjycnJ4c6dO5KBcf78eZ4+fSoVAgHV+lj//v3fei1kZGRk/m5Kly5NRETE33KuAQMGcPbsWUD1MCcEKBRw9swZ9PSUWPn7/y3zKA4LCws+/fTTD3b+Aj5KVcasrCy+/PJLduzYgba2NpqamowYMYJevXoRHx+Pp6enlJIIcPz4cTp27Mjt27fZsmULoaGhReppg8qYePHiBSVLlsTPz487d+5gbGxMWloaFSpUYNiwYTRv3hxQpTI2atSI0qVLS8eXd/fBu/Mgtn81EpGXj0BgZmVDs5HTMS1XAVC5YuyNtWltayQdl5OTg729PeHh4ZiamgLQtGlT7ty5Q1ZWFs2aNWPOnDno6OhIx9SsWZO+ffsWCaRMTEwkKCiIW7dvIwQMHDSQzwcPJj09nYYNG5KUlISWlhYGBgZMnz5dMozS0tJwdHTk119/lYKDZGRkZGRkiuOjNA4+Vu6l5rAhNomvm1Wh27w1lHV0k9oex0bz05wJpCe9wEhLYGSgz6pVq3B1dWXKlCnMmTMHY2NjjI2NcXd3Z+nSpZiYmDBz5kzWrFlDbGwsO3bskAqFvGkOYXcSGd2+CX2XhaJrYMiBr4YRH3GOEgb6GBoasmDBAqkQB8D333/PtGnTyM/Px9LSknPnzkmVykDlUfD29qZfv36S0MiSJUtYunQpmpqa5Obm0q9fP4YMGQLA4sWLSU5OZvz48X/exZWRkZGR+Wj46GIOPmasDZU0tlalV7564TaP70/NTn3Yd/oC16OvsWPHDjWvQ69evZg4cSJXr14lJyeHGTNmAKgJhLyNArWydct+oLJfU3QMDBFA+dpN6L3pJKsPn+WLL75QSy/atWsXGzZs4IsvviAuLo5Dhw6hLJS2k5OTQ79+/dTSc0BV/vTKlStERERw+vRp5s6dy+XLlwFVvfXg4OAi6ZIyMjIyMv8OPrqYg48dr1J6GCo1KG+oJAckrfGkR/c59cMMrqxTr8zYo0cPQFVlbODAgYDKINi3bx+gUjB7F+6l5nDwvkqq9NyOtfRa8nsQpFO9JoCqxkKgqzcPHjwgNzcXLS0t5syZw+TJk2nUqBGAVDuigGnTptG+fXueP3+utlRTUC8cVEsSOTm/127Q1tamUaNGbNy4UXpNMjIyMjL/HmTPwR9AUwENrAwZ4WHG566mjPAwY8a0KTx59BAzMzOaNWvGqlWriIiIKBIkmZGRQWhoKN7e3u91zgtPM9BAVWc8MzUZM+uKRfpoANPnzicwMFBKf4yOjubixYvUqlULHx8fFi5cKPU/d+4cZ86c4fPPPy8yFsC2bdtwcXHBxsaGUaNG4eXlJbXVqFFDrTyzjIyMjMy/B9k4+D9QaigwUGqg1FAwcuRIbt++TZ8+fXj+/Dl16tQhJCRE6rthwwa8vLyoWbMmzs7OjBs37p3PU1BjIR9IevIQQ1PzYvtd2ruVY3t2sGTp72peubm5xMXFceLECfbv38+PP/7Inj17SE9PZ9CgQSxfvhxFoSpghWnXrh3Xrl3j+vXrrF+/nuvXr0ttcs0EGRkZmX8v8rLCn4iFhQWdO3emc+fOVKhQgQ0bNtCxY0dAVR60INjvfSlcY0FbT4/c7KwifaIO7OTwsjn0WboDk1KFMizKl6dz585oampKSmlnz56lQoUK3L17VxJuevnyJfn5+bx48UISuSrAxsaGatWqsWfPHhwdHQG5ZoKMjIzMvxnZc/AnsXPnTmldPjc3l6ioKOzs7P6UsQtqLACUqlCJ1OcJ5GRmSO1RB0M5+P0sev+wHRNLK7UaC59++in79+8HVEsax44dw8PDAzc3NxISEoiPjyc+Pp5hw4bRq1cvyTCIjo6WxkhISODIkSO4u7tL+2JiYqSqjDIyMjIy/y5k4+AP0rhxY6ysrKS/hQsX4urqiru7Ox4eHujo6BQrFPUqM2bMwMrKijNnztCnTx+srKxISEhQ66PUUGBvrI0GoNTRxb66H7cunJTaQ74cSG52FutGdGNplwZUreIlVZgcMWIET548wdnZGR8fH5o2bVpELKU4vvvuO5ydnfH09CQgIIBhw4apCYvs37+fdu3avePVkpGRkZH5JyHXOfiHUFBjAeDe1XAOL5tLz4Ubi/Tram+MlaGyyP4/k+joaPr378/Jkyff3llGRkZG5h+H7Dn4h1C4xkIF1yq4NmhGVloq8Pub2Nja4C83DEAlu/rjjz++vaOMjIzM30hOviAtJ5+cfPmZ9/9F9hz8jeTkC7LzBNqaCkmx8XX4+PiQm5urts/FxYWvf1ytplamAByMtalaWu9vMQxkZGRkPjbu/abiGFvod9HeWBtf+XfxDyN7Dv4G7qXmsON2MvMiE1l09TnzIhPZcTuZ+6k5rz3m4sWLREREqP1t2LABK0MlrW2N1GostLY1kr8AMjIyfxk2NjY4OTmpPbD4+Phw7NgxpkyZgrm5OZ6enlSuXJlPPvmEJ0+eSP1mzpyJo6MjGhoaRTRv/Pz8iuzr2bNnkcyujIwMKQbqVQoqx978zTAAOLV5BcsXzGF9bBJ7w3/Fz88PY2PjIsfHx8f/obYzZ85ICpIuLi7079+frCz1LDIhBA0aNKBkyZLSvidPnuDr61vkwe9j5F9tHNjY2FC6dGm16n5Hjx5FoVAwbNgwjh07hkKhYOjQoWrH9ejRA4VCISmE9ezZk3LlyuHp6YmTkxP9+/eXxty/fz8+Pj64u7tTvXp1IiMj1cYq7oOblZHOkOZ1CY54wOVnGQQFBeHu7o6npydVq1YttrjQkSNH0NTUlL40Sg0FXTu0pWoVL+lDqqGhwe7du9WOe/r0KRYWFmqaDXv27KFfv35/4IrKyMj8V8nKyiI4OLjYti5duhAREcG1a9fQ1dVVC8Z+nxLxr2Ps2LHUqlWryP7ClWPzf9uXk5lB2Ial1OjUB4BzyZoMGT+FjRuLxmgZGRkxY8aM927z8PDgwoULREREcOXKFZ4+fcr333+v1mf+/PlFMtYsLCyoWbMma9eufafX/SH5VxsHoMrzL3zDDA4OxsfHR9q2t7fnp59+Ijs7G4Dk5GROnTpFuXLl1MYZPXq02lP80qVLefHiBV26dGHNmjVERUUxZ84cunTpIh1T3AcX4ExIsKSNcOBeGqOmf0NUVBQREREsW7aM9u3bk5//+xFJSUmMGzeOwMBAtTnt3LlTms+KFSswNTWlSZMman369+8vKU0W0Lx5cy5dukRsbOx7XEkZGZn/Ml9Omsy06dNJSk17bR8NDQ3q16/PnTt3pH2+vr5q0vHvy6FDh3jw4IHab2sBBZVjC3Pl0E9U8PBFW08Vo2VobIKiUpUipeMBTE1NqV279nu36evrSxo12dnZZGRkqBWTu3btGqGhocUWu+vcufM/ImbrX28cBAUFsXLlSkB1kz179qzaDVRfXx9/f3927doFwObNm2nbtq1UfvhVdHV1qVevHtevX+fWrVuYmZnh4uICQJ06dbh79y7h4eFA8R9cgPM71uLZpA2gegNuZP8u1VycmNFnn33Gl19+iZmZ2WtfZ3BwMF27dkVbW1ttX8WKFalTp06R/h06dGDFihWvHU9GRkYGVA856bmCKL0KlPaoSYexX7HjdjLZxQT9ZWVlsWfPHqn427swfPhwyfvp6emp9jD38uVLxowZww8//FDkuMKVYwsTd+kU1q5VpO184EZSNrn/a++8o6K6uj78zNCRYhcRFFGKShnEhr0QjSW2iL1giT1q7L23BEtiiSWiWBLFQnxNrLH3BggWRFAREBUbIEif+/0xmRtGiiafMe08a7Fk7rnl3GGcu88uv/2ekxRjYmJwd3endOnSWFpaMnz4cM28srP57LPPWLduHXp6evmO8/T0JDw8nJSUlPc6n/fNv944aNCgATExMSQkJLB9+3Z8fHzy/cHyGhCbNm1iwIABhZ7v5cuXHDp0CE9PTxwcHHj+/Dnnz58HYN++fbx69YqYmJhCP7hv9kbQfnAnTJpElSpV6Ny5M3v27EGp1Pxpdu/ejVKppH379oXOKT09ne3btzNw4EB52/3791m7di0LFiwo8BjRG0Eg+PtiZ2cnhzUDAwOpVasWTk5OeHp68sknn3D9+nV531evXmFmZqbz/x9457Dpxo0bcXV1RV9fP1+sXxsWzVFrVFpbDp/Mue3fcS3mEZG3I7kYFQto5OFVKhUlS5bk0KFDXL58WT7HkydP6Ny5M1evXmXkyJH5rjFw4EAMDAzIzs4mKyuLevXqAZrvtZo1a/Ls2TOaN2/OtGnT5Fh9eHg4bdu0pqDHffKTBMxL6UrMS/DeKxjs7OwICwvj8ePHZGZmEhQUBMCcOXPo3Lkz1apVK/A4fX19SpQoQUJCwnudz/vmX28cAPTp04eAgAA2btxY4IO/fv36xMbGcvjwYfT09GSJ4Lz4+fmhUqlo0aIFXbp0wdfXF0tLS3bv3s2UKVPw9PTkyJEjVK9eHX19fR3J47wU1BtBAmbPX8Tdu3fZuXMnEydOJCsri8ePHzN//ny++eabIu9v9+7dODo64urqqjmfJDFgwABWrVpVqMSx6I0gEPz92bRpEzNmzGDLli1ERkYSHBzM7NmzdR4sgYGBeHp6EhQURGpqqs7x7xI29fT0ZOfOnfTs2VPn2LxhUe13WQnrirh/3JmdM0eib2jEPSxJycqlV69eXLlyBTc3NywtLbl48aJ8nrFjx8oibEuWLCEgIIArV64AGk/DihUr2LJlCzdv3iQ0NFRO4Fu3bh1PnjxBoVCQmppKaGgoERERODk54ebmhrGRMXcv59daMTAxJfuN5EAFvLVC7I9iZmZG9+7d+f777wE4deoUK1euxM7OjoYNG5KSkoKdnZ2OuN0/QX7+P2Ec9O3blxUrVmBsbIyDg0Oh+/Tu3Zv+/fsXOK7NOQgJCWHmzJlyfKlZs2acOnWK4OBgli5dSkJCAtWrV9eRPM5LQb0RFCBLHnt7e/Pq1SuuX79OcHAwjx49QqVSYWdnx+7du5k7dy7Tpk3TOd7f319n1ZCSkkJ4eDjdunWTOyoeOXKEFi1ayPv8Ez6cAsF/nVmzZvH1119TvXp1eZunpyetWrWSX/v7+zNp0iQaN26s0+wN3i1s6u7uTrVq1WRvpZbCwqLNB40l6tJJJEmNAniYplnNz507lx49euDj40NYWBiPHj0CICwsTM6XMjY2pnHjxmzduhWAhIQEGjduLK+yjYyM5NCoQqGgSZMmREVFER0djZeXF1ZWVnIDuF49e3Br39Z8c7SqWp1nD6Ll10o05d7679E4iI6OlpPSs7Ky+PHHH2V5+TNnzvDgwQNiYmI4e/YsFhYWxMTEUKaMZlGoNXhsbW3f23z+DP4TxoG1tTWLFi3iyy+/LHSf/v37M27cuN8VKwPk/wAA8+bNo3nz5lStWlVH8jgvb/ZGkLKzMX8ZJ1u1ly9fJjExEXt7e9q2bcuTJ0/k/gddunRh5syZOqGC6Ohorl69So8ePeRtlpaWPH/+XD5uyZIltGzZUieMIHojCAR/b7KysoiLi8PLy6vQfW7dukVcXBytWrVi4MCBBVYT/J6wqZbCwqIAxmYWIEmkpyQhAc8zckl49Ehu/16+fHkcHBxYuHAhAAYGBrRs2ZLz588zYMAA1qxZw507dwB4/fo1WVlZeHt7o1Kp+Pzzz+WH7pAhQzA3N6ds2bKUK1eOtLQ0SpcuLc/Dy8uLiIun883R1fsT7lw4Ib/OSH/N8EbV8fHx4datW9jY2DBlyhT5+jY2Nr977Pjx43h4eODu7o6HhwflypVjxowZb31fQVPh1qlTp3zG2N+N/0xXxsI8AlrKli37u9ooa5k5cyZnzpwhJycHLy8vnf+ctcuacCc5S2f/vL0RnBu1JDsnm01TR/Btagr6+voUK1aM3bt3U6JEiXe6/saNG/n000+xsLD4XfP+N/VG+D3iUgLBvwl/f3/69u2Lnp4ebdq0YciQIUREROjEu98lbPomb4ZFJ+0PkX9PS3qOnoERC65oKhJsanjw48hOBO3ZLXtUW7ZsKecW/PLLL4wfP57Q0FDKli2Lvb297GL38vLi4cOHHD16FDMzM/r370/58uUZM2YM+/btQ61W8/jxY5RKJb6+vjpVD1ZWVrx88ZymZfQ4+TQXJZocLiuH6piVLM3Dm6FUqOHBJ45lmPmw4BCqqalpoeHVosYGDx78TuXgdnZ2JCUl6WzbsGED69evf+uxfzX/auMgJiamwO2zZ8+Wf9cm5RR1bEBAQKHX+O677wod00oeH45Lkz+4AE18R3F8/RKcG7XUfHAvni/0HHkpaB5a67wofH198fX1lV8/e/aM4ODgf0Q5TVEIVTTBvxlDQ0O5KdubZcygyYrfunUrBgYGci3+69ev8ff3Z8mSJTr7asOmixcvfrdr/xoWLShvytDYlNzsTCRJQqFQ8DI+hvi4wtu/ly5dWue7a+jQoXKFV8WKFVGpVPJiqEePHixatAiA9evX07NnT4yNjQGNlkLe77uMjAz09PSoY22JTfFcHeXY9hMWYpB4/4P0mvk9PHnyhGHDhhWarPh34u/t1/gX4FHahN4OljhYGso5CBVdatKiXQc6WinxKP3h4/53795l7dq1OmWPQUFBeHp6ykJPzZs3R61WF6hgpuXo0aM0atSIKlWqUKtWLVq0aCE3YypKFa2oMdAkVFauXFknRwIgNTWVVq1aUbp0acwti+cTl5KA6OQstkUlE/rst5bWP//8M0OHDs13jrzKZQDXr1+ncePGODs74+LiwoABA0hP/+08Wl0LR0dHatSooeNpKmwsLS2NunXr4u7ujru7Ox9//LFseGZkZODp6Vlg+apAAJqFzNixY7l9+7a8LTQ0lCNHjrBv3z7s7e15+PChHEK8ePEiW7du1RF+g98fNi0sLApgbG6BRZnyPI+7jxJoXEtVZPv358+fy/MJDQ1l7969ctlfz549OXHihKwuePDgQTncaW9vz5EjR5AkCUmS2L9/Py4uLoBm9e3p6YmBgQE1a9akXcPazOncmDopt/jcpSQL2tViwaCufyvDADQiSG8mfv5d+Vd7Dv5KCuqNUK16DTZs3qpxf3uM+ItmBnXr1tV5/ejRIwYPHkxwcDCVKlUCICQkREfU402OHj1Knz592LNnD/Xr1wcgKipKVoj09vame/fuBcY3ixoDOHbsGMWLFyc8PJz79+9TubKm7NPAwIBJkyaRZWxOp1beAPnijdrXh+PSKGOsj42ZAVOmTOHnn3/WOUfJkiVp2rSpzrHGxsasWrUKNzc3cnNz6dmzJ19++aXsaRowYAANGjSQs5IfP34sH1vYmImJCUePHsXc3BzQqKaNHj2a//3vfxgbG9OnTx+WLl3K3LlzC32vBf9dBg4ciImJCb169SI1NRV9fX2qVKnCokWLmDBhQj5hoGrVqlGhQgV++uknSpYsKW8vKmwaEBDA9OnTefnyJXv37mXJkiX89NNP1HZwyRcW1eLi/QlRF05QuqI9tcsWvcC5fPkyo0aNQl9fH3Nzc3bu3En58uUBTcijffv2eHh4oKenR40aNVi7di2gMYwGDx4sGwTOzs6yt3PQoEE8fPgQPT09pk+f/g7vpOD3IhovCbh27RqtWrUiOjpafohpadq0KWPGjNGRXwaN4FOPHj3kFUBhFHZ8UWM9evSgUaNGREZGYmFhwbx583TG156+zhdtGzLr9N1Cr6tEE2Io/TCMqVOn5msvHRMTg0qlyhcPzMuSJUu4ceMGAQEBREdHy8pvbyYSFTWWF0mSmDt3rrx6Ao0R4eHhQUJCQpHGmEDwVxD6LD1fWBQg+VE82yYO4H8nzlKzjOkHn1dWVha1atXi+PHjOkmKgveHCCsIcHNzo2HDhlSqVIlOnTrh5+fHw4cPC90/Wy0RHBxMrbr13vtcXrx4waFDh+jZsycDBw4kICBAR0o6Wy1x/1XhDau0aMWljp04kc9T8i6kpaWxYcMGOnToACBnKw8bNgxPT09atmxJaGjoW8e0eHt7Y2Vlxa5du1i9erW83crKChMTE27evPm75ygQ/NkUFBZVAHWc7ZkxZRJlM1/8JfO6f/8+ixcvFobBn4gIKwhQKpXs2bOH27dvc+rUKQ4ePMiCBQu4evWqzn55EwBzJNh2J4n4EinvNQHw+++/p3Xr1hQvXpzixYtTrlw5Dh8+TOvWrQFNFvW7IgGxcfFUcyxY26IwsrKy6NatGy1btqRTp04A5OTkcPnyZRYuXMi6des4ePAg7dq1IyYmpsgxrf760aNHUavVLFiwgAULFug0adEKUmndpwLB34H27dsTGxsrv5YAy+IlOHb8uKYqyP73lX2/T5ycnN6p6kLwxxGeg785eWVUtbzZJbJPnz68fv1a5xgnJydUKhVOTk46GcoxMTE6iXixsbE4OzuzbNky7OzsOHjwILdu3SI3N5c2bdrICXlvdpes4OzGg/CrRCdnsTH8EdVVNXn16hWgSX5ydHTE3d2d0NBQnQZPeaVa3ywT2rhxIxMnTmT79u2ULFkSOzs77t+/j7+/v3ycpYkhV/d+r3PcgeWzuHZwT773TgGYFzMlIyPjnd/v7OxsunXrRvny5XWUKStWrEiFChXkjOzWrVuTlZXFgwcPihzLi1Kp5LPPPpMFYLQIQSrB35F9+/bpNJsLu3aN0ydPiHLh/wjCOPiHolVsDAsL4969e6xatUpnPDAwkGvXrnH8+HEWLVqko3Wu5fbt2zRp0oTBgwfLrvfBgwdz8eJFrK2tadq0KZGRkTxLz8nXXbLZZ+M4sWEZMeFXuRDoT4X6rQi7/5Ddu3fTqVMnbt26RVhYGBUrVsTPz0++ZmFSraBJ3rOwsKB3797MnDmTmJgY7t69y+HDh6lcubJ8XEljXYdX434jObruK9S5ufI2rSqayt1dVlR7Gzk5OXTv3p2SJUuyfv16nRwAT09PLCwsCA8PBzRJVpIkYWtrW+TY48ePefnypc7fRaukBpCbm8vdu3dl6WuBQCD4OyDCCv9wjIyMaNiwYb5VqpYKFSrg7OzMgwcPqFOnjrw9ODiYjh07snLlSjw8PBg8eDD379/H1NSUnJwc+vXrR8uWLdmyZQtjRwxBYfBb58ieX/rj6NWMLrNXcODrWcRdD6GkTSWGXzvPt18toGHDhsyfP5+1a9fy9OlTsrKysLGxITQ0FHd3d+bPn8+ePXvIzMxk0KBBjBw5ktDQUM6cOUPv3r15/vy5fK3ixYvz0UcfERoaytixY/n555/JzskhMy2VRR+7YV+rId3mf0spGzuiLp7AqcFvVQy1y5pg1K4dc+fOJTc3V2645ebmxtOnT0lJScHGxoZmzZqxdetWAgMDCQoKws3NDQ8PD0DTuGv16tUoFAo2b97MZ599Rnp6OkZGRuzZswcjI837UthYbGwsQ4YMITc3F0mSqFKlCtu2bZPv7+zZs9SuXVsns1wgEAj+akS1wt8cOzs79u7di0qlkrf5+vqiUqkYM2YMycnJtGzZkkWLFtG8efN8x9y+fZt27dpx4cIFypQpQ0xMDI6OjpiYmLBz504djfY36dOnD8VLlMCm/8wCxVBA02VyZc/mzDgeiQIY615Kx+04Y8YMwsPDZW33gu7hTd5lrEnvITpZ1MfWLyEz7RXtvpiDGmhlW0zWkBgxYgRNmzbFx8en0Hv9q+jevTsDBw7ko48++qunIhD8ZQiV078fwnPwD8XPz4+NGzdy584d2rZtK8e7tXTr1g2lUklkZCTLly+Xm36App6/RYsWrF69mmbNmumIIWlZuHAh0dHR7Dv0C/73Co/Z5+0yKaFJGNT+5962bRs7d+7k9OnT7+GOdfEobUIZY31ZFc28VFkS70XiYGlI7TcSJOfOncvBgwff+xz+v2RkZNCkSRNhGAj+swiV078vIufgH8qECRMIDw/nzp07XL16VRYO0RIYGEhERARHjhxh8uTJOv3flUolgYGBGBgY0LlzZ1mdTMuSJUsICgri4MGDFDcvVmB3SS15u0zm7S4ZGBjInDlz+OWXXyhXrtx7uec3sTEzoJO9BdUeXuLipqXEXTnFnM6NadewNiqVSu5QV6pUKXr37v2nzOH/g7GxMcOGDfurpyEQFIg2GdrX11fuk/Amp06donbt2tSoUYPq1atz4cKFt553/Pjx7Nixg5Cn6Szee5IvOnkzo35Fto7tq6NyOmfleiwtLVGpVKhUqnwLoMKuvWDBAvkYlUqFhYUFY8eOBSA8PFyufBIUjfAc/ANIz1aTrZYKdLdVrFiRlStXMmTIEHx9ffNlvXt7ezNs2DCmT5+u49o3MDAgMDCQHj160LFjR3788UeMjY1ZtmwZ27dv5+jRo3JVg4OlIdGFdGjTdpnMzUinejlLDJQKdu7cyfTp0zl69CgVK1Z8n29FgbRv15aD7dvj5ORUYChCIBC8fxISEujXrx8HDx6kWrVqZGZm6siNF8TDhw85cOAAo2Yt5IfoFCxKl6Pd+Pkk3L7OnfOarrHa75kbLzKp16gJh3/e97uuPW3aNLmtfWZmJtbW1rKSpJubG0ZGRhw/flwOwwoKRngO/qbEpWYTdC+F5Cw1LT/+mNLlK1CqfAXKV7DJVwLYvn17nJ2ddWrn8zJjxgzOnj1LcHCwznZ9fX22b9+OhYUFHTp0ID4+nnHjxpGUlESzZs1QqVTUrVuX2mVNCjQM4Lcuk1FXzsgyqr169SIjI4MOHTrI1rs2yTAgIAAbGxt27drF7Nmz5UTF/8+YJEkcO3ZM1iQQCAR/Pt9++y09e/aUmwgZGRnl61fyJtouslefZqAELMtZY+tSE/0CQpsKICmz4G+ed7323r175YoiLT169PjHN537EAjj4B14m3vtypUr1K9fH1NT03xSwAEBAbJrzN3dHTc3t3zJeW8S8jSdTeGPGNWuMWN2nmba0VvU8+mP0siEJ48SaNP3M50VcmJiIkZGRqxduxYXFxe2bNkiJzAmJibSo0cPSpYsSb9+/YiNjdWRDNbX12fIkCEcPXqU3bt3I0kSd+/exdvbm4kTJ3Lp0iW5uyTk/8Ao0XSZvPvzVjlGmJ2dTVxcnE6NdKlSpQBNQmF8fDxpaWkkJSURHx8vVwb80bHDhw9Tp04duS+EQCD487l16xbp6el4e3ujUqn4/PPPSUtLK/KYkydP4lm7DlGFeCLzIgE3rl7AXaWifv367Nq163df29/fn4EDB+ps8/Ly4tixY+96m/9ZhHHwHihfvjxff/01y5cvL3C8WbNmsibB+vXrGTRoUKHnikvN5kh8GhcC/anWtDVGxcwAqFq3Cf1X7sCuphehzzKJT/1NQnjy5MnUq1ePqKgoNm3aRM+ePeUuaEWNASQnJzN58uR8LWEnTpzI7Nmzyf1VO6AwGVUHS0OmdGpG/+4+sgjShyY5OZmvvvrqL7m2QPBfJScnh9OnT7Nr1y6uXLnCy5cvmTVrVpHHxMfHU7JM2UKrn/Li3Kglk/aHcv5KCP7+/owdO5aLFy++87UfPHjA2bNn8zWnsrKy4vnz579LHO2/iMg5eA/Y2NhgY2PDrVu33rpvUlKS3Lu8IK4kpqMELgdtYcDqnfJ2W5ea8u/KX/fTrtR37txJdHQ0ALVr18ba2ppTp07h7e1d5BjAyJEjmT59OkFBQTrzKFu2LFWqVOHIkSO0bt1ap8ukBEgS1KhRg0k/aNQKC+uw+CF41za0AoHg/VGxYkVUKpX8fdajRw8WLVpU5DGmpqbkZmWiMOatBkKxEqXkJOdq1arRpk0bzp07R7169d7p2ps2baJDhw75NEQyMjLQ09MrsEpL8BvCOPgAnDhxApVKxevXr3n48KGcRf8m2WqJqOQsXj5+SEZqCqVsKxe4n7apULZaIuXlC7Kzs7GyspLH7ezsiI2NlfuoFzQGsHv3bpRKJe3bt89nHMBv7rfWrVvn67MgEAj+W7ypRdCzZ08mTZpEZmYmRkZGHDx4EHd39yLP4ebmxt2oOzg0VxWa5KzlVeIjajlUwkCp4MmTJxw/flxeCLzt2mq1mk2bNuHv75/vvBEREbi4uBTZQVUgjIMPQrNmzeQWvTdu3MDb25uQkBCsra119svKlZDQ1Q4oDK2mwB/l8ePHzJ8/n5MnTxa6j5WV1Tt5QwQCwb+XtGw102bOZtai30J3n81YxBjfnrRv3x4PDw/09PSoUaNGvpLqN+nSpQtbtmxhWfd+3EnO4mlMNBuGdiY7I53szAwWfexG0wFj8Oo6gPOB/uy+cIQ5Roao1Wq++OILucKgfv36RV776NGjKJVKWrRokW8Ohw4dokuXLu/p3fn3IkynD4yLiwsVK1bk3Llz+cYM9RQaN1oe7YDC0LrbSpUqhb6+Po8fP5bHYmJiqFixYpFjwcHBPHr0CJVKhZ2dHbt372bu3LlyCRCIhkACwfsmWy2R9mtp8tv4/yRCA8yfP58qVapQpUoVnf/XeZOkXVxcaNasGXfu3JHHtY3dihcvTpeevbkaEcWwgINMORQu/5Rt0JZtUcl49x/JrVu3uH79OlOmTNGJ73fp0gVra2sUCoWcBN22bVtu3brFx3VVbOrTnO2TB6Gnp1mjzrsQx5RD4ZSuUIlVvbyJv3SMEpYWbN68mfDwcIYPH46Pjw/nz58HNFov2mvv2LFDp1qhZcuW3L9/X6c/Cmg6ru7Zs4ehQ4e+9f3/ryOMgw9MfHw8UVFRODo65hszUCpwsDSk7K/aAdkZBdcMa5sKaXUPfHx8ZKv5ypUrPHz4kCZNmhQ51rZtW548eUJMTAwxMTF06dKFmTNnsmDBAvk6ERERb3UTCgSCt6MtTV4W9pyVN16wLOw5QfdSdBKLfy9FJUKfPn2a7du3Ex4ezq1btzh8+DD79++Xx7VJ0jdu3MDT0zOfPsiECRP46ewVBn1/EqeG3hxeoxvP14YDDselyfcwZcoUJk+eLO8zdOjQfB1llUolW7ZsYd26dUTeCOdycCj1vD9G1fpTANJTktg5YxibNwcQdfM6fn5+OgbHtGnTdK7xe7l//z6LFy+mdOnSf/gc/xWEcfA70dbYa3927dpFZGQkNjY2jB07lsOHD2NjY6OjOaDNOVCpVLRq1YqFCxcW+tCtXdYEvV+1A+5eOSNvP75hKYs+diM2/Cq7533B8EbVefr0KQBffvkl58+fx8HBAV9fX7Zt24aBgcFbx7RkqyVy1BK5edpsCO0Awb+J91WOXNBKe+rUqTg7O+Pu7k6tWrU4fPiwzvFvtjsHTVhw9pDeLNh9lNBn6ezfvx9PT0+MjIwKFPIKCwvD1dUVFxcXXFxciImJwcbGhgMHDjB+/Hj5O0b7IA0MDKRPnz4UK1aM5ORkIiMjdVbLjx8/ZvDgwQC0aNGiwMZtVxLTUUgSmamvMDEvXuD7qk2Ojo2N5ebNmzRq1Ii5c+eiUqkYP348LVu2BKBRo0bcvXsX0HQ4bdiwIQCl9XO58NMuvpk4gs9dStLa5CXly5SmRW2VfFxsbCwhISEAqFQqnj59SkRERIHzeRtOTk75KrMEBSNyDt6BmJgYQPMlURhvChNp8fX1xdfX952vpdUUiPMdxfH1S3BupPnP1XzQOLwHjcvXVAigXLlyHDlypMDzFTWWV9fc5Yul5ABB91KoU9aEG2ePCe0AwX8G7So8NDS0wD4cefOGxo8fz5gxYzhw4ACgeYDNmDEDExMTwsLCaNy4MQkJCRQrVkwuTQZ0ku/iboTwOjmJSu61ORyXRn1rOzZu3MiuXbtITU3VufaLFy+4ePEi165dw9ramlevXskdRkGTOGxqairPDyA2NlZ+AA8ZMgQvLy/5AQuafKLg4GAiIyP58ccf6d69u841/fz8kNZsIO3lcxR6egzZkF+lUHtPd5KzSAo/Se3atQGYOXMmM2fOlPdRKBScOXOmQJGioKAg7O3tqV1To1lSzcmR58+fc/78eerXr8++fft49eoVMTEx1KxZU77fY8eOyQJIgj8H4Tn4i9GuaPLyzfhh7JnUn6d3b/FN18as6N6U4P/9gIOlIcFLxtLOvSoqlQpnZ2eGDBmio1tQEI8ePaJevXqo1Zqvp1GjRmFdsRIVzQ05fTlYZzWzdNo4XB2r0Lp1a/r27Ztvrk5OTrIXRFt1kZGRQceOHXF0dMTd3Z2PPvpILp8E6N+/P25ubqhUKmrXrq0jQJI3higQ/FXY2NhQp04duQV3Uby50m7durWcm+Pq6ookSbJXT1ua/CaX92zGvXVnQPMl/NzSFnd3d/T186/Xbt68SdOmTeUEZnNzc0xNTd/pvvz9/alcuTI1atTQ2X7ixAk55+j48eMMHz5cZ3z02PGM2nGSKYev4z1kIt9PKLxUWQJi4+L/UA+VN0WKLC0t2b17N1OmTMHT05MjR45QvXp1nffFysqq0MWY4P0hjIO/kFq1apGQkEC3bt3kB67WLTh54gSeJcQTG3mTqBvh/DDzczrZW1DMQMmECRN01AffliE8b948RowYIZfuNG7TkX7rf6J4edt8pUQuLT5h6MafKV7eFsksvx5DYGCgfN28+gKDBw8mMjKSsLAwOnTooCP0tHz5csLDw7l27Rrr16/Hx8dHNlT+vzFEgeBDolarC1xpa9m0aRP29vZUqlRJLk0uqFzvXvB5bF00kr55S5MLIikpiaSkJJo0aYKHhwczZsyQxclAExI5ceIEzZs358SJE4BGgyA0NJS1a9eyYMECnj9/rpNc3KxZM3bs2EG1atVwdHTMZxzoKZHFztxaduRhRBipL58VOD8FYG5m+rtFhe7fv8/Fixfp2bOnzvZmzZpx6tQpgoODWbp0KQkJCVSvXl0eF4nSHwZhHPyFXL16FWtra50H7vfff6+zj4FSQTEDZYFNl4yNjWnSpAmRkZGFXiMjI4PAwEA+/fRTeZvSsRYlylkXuH9lz/pYlrNGAdx8UXTFRN55tGnTRs4MrlevnhyKAXTcicnJyTrH/n9jiALBh0Ab0y9dunSBK22AY8eOMWfOHAIDA1EoFHJpckEkP0nArNRv5cpFlSar1Wri4+M5dOgQZ8+e5fz586xZswbQJP0tWbKEZs2aMW/ePLp168aDBw/o0qULq1evxs/PD6VSyZkzZ6hQoYLOea2srEhISGDDhg0cOHBA7lUCoKfQJEcrgbuXz1CseClMLXXFhOC35GgPd/civ4cKYuPGjXTq1ClfuOHRo0fy7/PmzaN58+ZUrVpV3iYSpT8Mwjj4m+Ln56fTdvTMmTP59nn58iWHDh3SaSryJleuXKFy5cqyG7Ko1UxeJOBBana+1Uzfvn1xdXVl4MCBsuv0Tb755hs6dOigs23y5MlUqVKFzp07s2fPHh0BEqF1Lvi7o83uj4+PL3ClferUKfr3789PP/2Ek5MT8FtpckEYGJuQk6dVet52529iZmZGTEwMDg4OODk5ERISQmBgIJGRkdSqVYsJEyZw+PBhunXrRqlSpbh69So1a9ZEkiQ++ugjzMzMePz4MeHh4Tp1/9oVuLW1NePHj9fJE/Dz82NGx0Ys79aU4xuW0tPPv0DRIDWaJOqGDRsSHx/Pixcv5LG2bdtiY2MDaNRUmzZt+ttxajUBAQH5+h6AJmfB2dmZqlWr8uDBAx0ho7S0NK5fvy4rvAr+PERC4t+UCRMmFNp+2M/Pj4CAAJRKJV26dCky4TE+XjcWWNRq5k20qxmt1+L06dNUrFiR7Oxspk+fTr9+/eSkLC0LFy4kOjo638N+8eLFLF68mKNHjzJx4kTOnTsny5eKGKLgn4KpqSkbNmzAycmJ0NBQPDw8OH36NH369OF///ufzopWW5pckBJgeYfqPHsQTXGrCijR9Ch50zuo9b59+eWX7Nu3jx9++AG1Ws2nn35Kw4YNcXJy4uLFi/IDOCoqioYNG+Lq6oqlpSWvX7+WzxUQEMDevXvlpEVfX18CAwPl+ebtS5A38Tr0WTqH49JQoptQqX3dyraYLOM+YsQI/P39mTBhAoBO6eSbKJVK4uLiChz77rvvCj1u69at+Pr6YmZmVug+gveD8Bz8A9HmHISEhDBz5sx8Qh95MTXVjQUWtZp5kzdXMxUrVgTAwMCAMWPG5PNmLFmyhKCgIA4ePFhowpS3tzevXr3i+vXr8jYRQxR8SP5IOXJe3lxpDxw4kMzMTPr37y97+rSf78Lanbt4f8Kd85r8ADWQeesCNjY2LFu2DH9/f2xsbNi3T1Mh0L17d2xsbKhRowYqlQpra2tGjx4NaHJ2XFxcUKlUdO/endWrVxeooVIQ76IUWFTDtd4OljpVU6NHj/7TH9pKpZIpU6b8qdcQaBCeg385bm5uOrHAvKuZolAAlcwM5NVMWloa2dnZcnxw+/btcstkgGXLlrF9+3aOHj2qE0PMzs7mwYMHcszw8uXLJCYmYm9vL+8TERHBkCFD/p93KhAUzvsuR8670o6Kiir0nNrS5DdX357te7DWty1ZQyfwiWNZPDxa0b2Q6yuVSpYsWcKSJUvyjW3evLnQaxd1D8+ePSM4OJh169a99VgbMwNszAy4EhLKwP79USjQWWD069ePL774AkNDQ4YNG/ZO8/mjaLUZBH8+CkmS/rhAv+D/jZ2dHenp6TrCRM7OzkRERFCmzG8JS7169WLChAn4+vqiUqkKDTkUhKenJ1u2bJHLmXoN+Iyf9+8n9XkippYlMTQtxoR9VwD4cf44bp/9hdTniZQsWQpLC3Oio6O5d+8en376Kbm5uUiShL29Pd988w12dnbEx8dja2uLvb095ubmABgZGXHp0iVev37NRx99RHJyMvr6+hQrVkxOMgKN0eHk5MTt27eFq1DwryX+V02RO78KISmAjBvnaeBki3cdj7cd/t65dOkSubm51K9f/4NfW/DPQBgH/wF27drFyZMnWb16tbztXWKJeV2GfxZr164lPj6e+fPn/+nXEgg+JEOHDuXixYs62yTg2OlzWJqZFliBJBD8XRBhhf8APj4+PHnyBLVaLWcce5Q2oYyxfr7VjIOlIbXLmshJRn82IoYo+LfyNv0RgeDvjPAc/AtITEyUNczz8tFHH+Hn5/fW49/s0y4QCP49iP/fgj+CMA4EAoHgX0je3il5PYN1PqBnUPDPRRgHAoFA8AGxs7Nj79695OTkyDLjL168IDk5mcqVKwOaBOQyZcowevRoeRvAhg0bqFWrVqHnDgsLY+rUqcwL2M3PUYlsGNKZ7F/FlsxLl6XztCUUt65ITYNklo4bTkxMDEZGRjg4OLB27Vo5Cbply5Y8fvwYpVKJubk5K1askKuTihpr1KgRW7Zs0Zmz4J+JMA4EfyrCpSkQ6KI1DlQqlbztTZGiwra9jTZt2jBg9ASiy7qiVqvJTn+NUTFNFdDZbWu5F3yOvsu38up5Ip7qRDq3bApotFOePn0ql3omJSXJJck//vgjs2fPJiws7K1je/fuJSgoiC1btvzu90Xw90IkJAr+FIRLUyD4sMTGxnLz5k2UDp4ok7NAqZQNA0mSyEh7JQumWZYqi8LSRj62bt26rFq1Sn79Zj+UvEJrRY21bduWzz77jOTkZCwtLd/3LQo+IEIh8V+KthW0r68vX3/9db7xK1euUL9+fUxNTenYsaPO2I4dO1CpVLi4uODi4sLSpUvlsZMnT2JiYiIrwdWoUSOf3GnI03S+j0om+lfDAEAtSYz7tCUrT90g9Fk6AN9++y3VqlXD1dUVd3d3Wclx48aNuLq6oq+vX+Dcv/32W5yrVaOGiytueY6LioqiWbNmcjvrcePGyd0fV61axcKFC//AO1k02WqJtGx1oR31BIL/D9qGTyqVilatWhW576lTp/CsVTtf75QNQz9l4Uc1uHF0H+0nfwnodoLMzc1l1apV+fqh9O3bF1tbW2bMmMHWrVvfaczAwABXV9cCe8EI/lkIz8F/lPLly/P1118TGhrKwYMHdcZsbW05dOgQVlZWJCcn4+npiZ+fH5aWlnKr2Fq1apGTk4OdnR0jR46ke/fumJub88XUGVyOSaRsZQcu7Q4AIOnxQ5AkUCjYOrYPL8bN5+GBLZw4fJAqVapgZGTEhAkTZCEoT09Pdu7cyaJFi/LNu1Y9L54mpTBg/X7uX7vI4ZULMLOwwPezoTx7GEunTp0YNWoUr1+/xtbWlh9++IFixYoxcuRI/P39GTFiBGfPnmXmzJncuHGDYcOG6RggT548YdiwYURHR5Odnc2QIUNkwakrV64wevRorl27RqPm3gxZsU32jNw+fYSHF46wacN3wjMieG80a9bsncMK8fHxlC5bNl/vlEFr96BWqznhv5wT/svpOOUrQKO5kJmjZtznwylRooQsyaxFGxrYvHkzkyZN0umjUtSY6JXy70B4Dv6j2NjYUKdOHYyMjPKNNWjQACsrKwAsLS1xdnYmJyeHwMBAuenMhg0bAE1fhGLFiskP9oS0HBRA3S6+jNpxklE7TlKtSStMS5Si55f+jNpxEofaDbl+M4KdO3dy48YN/P39GTx4sOwBcHd3p1q1agQFBbFw4UJ55VSpigPXw6/z4ulTVvVtyYHls8lIe0Ul9zpEvMwkJVstt4R2d3fn5cuX7Nu3j8uXL7N8+XJq1apF8eLFGTt2LKmpqVhaWsrSt8ePH6dOnTo4Ojpy5swZPv74Yy5fvkxAQABXrmjUI7UG1RdzvyQ+LYfo5CxunT7CjwvG49y4JTdDr9KwUSNKlCqdrw3t9evXady4Mc7Ozri4uDBgwADS09PlsbwdOO3s7ChZ8rf2uJmZmYwcORIHBwdcXV3p3bu3PNayZUvc3NxQqVQ0atRIp+1uo0aNuH///h/+jAj+fLSep9z34HkyNTUlOzOjwN4pSqWSOp16E7p/p7xNAUwaO5q4uDgCAwML7LoIGnnkEydO8Pz583caE71S/h0I40BQJLdu3eLChQsYGxvL2yIjI1GpVOzdu5clS5awePFijI2NyVZLPM/IzbdykdRqXj6Mxda1JqBxaT5PfMy18HAaNGggN64pqAV0v379uHbtGj+dvUJZ1zpIkkROdhYGRsYYmpji2aEHD8Ku8Op5IrWHz+GHwJ2ULVuW6OhozM3NSUtLo2TJknTr1k1+GF+6dInIyEg6duzIkSNHePbsGSVKlGDHjh3Y2tqyc+dOzp8/z549e2jcuLHsNrWxsaF8dQ/upCHfx+FV82naX7PicvVuj0XZ8vRZvSvfe2BsbMyqVau4ffs2YWFhpKWl8eWXGhevq6sr165dk3/atWtHr1695GMnT56MQqHgzp07XL9+XUdjf+fOnYSHh3Pt2jXGjh2ro58/btw4nR4Agr8Pj19nE3QvhWVhz1l54wWH4lJJSMshPjX7D5/Tzc2NqDt3cLA0RAm8evaE9JQkeTz8yF7KO1QHNF/8p7+ezr27d/nxxx/lDqmgSThMSEiQX+/du5dSpUpRsmTJIse0RERE6HSnFPwzEcaBoFDi4+Pp0KEDa9euRV9fn27dusmlV7NmzaJjx45Mnz6dBQsWEBISQlZuwaufnKxMFAoFRqa/9U5Q5+Zw7959Tp8+La+E83ZqfJMriencCz6PQqE5tvPMb+i/KpDrR/6HkWkxMtNSubRrE56tOzNw4EBKliyJvr6+LMtsZ2en08IWNN31DAwMiImJwcPDA3t7ezw9PdmzZw/u7u7cvHmTw4cPy017tPPQrszuh1zAxMyCEta2mmt41ONF3H1MzS3JeaMVn4ODA25ubgDo6elRu3ZtnfNqycjI4Pvvv5f73KelpeHv78+CBQvkxC+tVwfenhx28OBB2Zsi0BAUFISnp6ecm9K8eXPUajVNmzbF0NCQxMREed979+6hVCrz5eWcOHEChUKRLxY/e/ZsypQpg4eHB46OjtSuXZtvvvlGDselpaWR8OgRbRt74eNUiun1bFjwUQ2SExNIy1GzLSpZzsnJS1hYGG3btpVfd+nSBWtraxQKBUlJSQA0bNiQ+Ph4HPTTUQNHVi9iblMHlnSoy9ddG3Pv6jm6zl8DwIGV8zmwZR3Xr1+nbt26qFQqKlSowPnz50lOTqZjx45yLtCqVav4+eefUSgURY6BpsFVbm6uMA7+BYicA0GBJCQk4O3tzfTp0/Hx8WHChAkEBgaSlJTEmDFj6NSpE/v27aN48eLUrVuXY8eO4arS1Dq/2UJaqaeH+teGTdqx4lY29OjRg5MnT7Js2TJ69erFpUuX+OSTT3SO3bx5M0d++YWn6Tm8iH9A6YqVyUh9hVJPSbESpbB18STs0B4sy5bnwk5/xu45z+aBrSlVqhSurq7s379ffjhqv6C13Lt3j9zcXBwcHORtS5cuZcSIEQQFBVGzZk2aNm0qezSy1ZKcYwBwL/g8tq6e8rFmpcuRnJiAhCYBM1stFVi+mZaWxoYNGwrMqQgKCsLe3l4uc7t79y4lS5Zk4cKFHD16FBMTE2bPnk2LFi3kY/r27cuJE5r2v3ljv3mTw9q1ayfKSoFHjx4xePBggoODqVSpEgAhISHy59LNzY2tW7cybtw4QJMc6+npme88/v7+tGjRAn9/f/r06aMz1qtXLzmP5d69e/Tu3Zu7d++yYsUKnuXqM+1YZL7ywuaDxsnHH45Lo4yxvk4nxSlTpujIjA8dOpRvv/2WcuXKydsMDAwYMWIEhwK3UMG9LinPHlOivC09v9qAtZMroFkNPk+I5eWNi9SrV49JkybJhs+1a9cYNWoUp0+f5vLlywW+f5UqVSp0DDSS0RMnTiyyjbzgn4HwHAjy8ejRI1q0aMGkSZPo169fofuVKVOGhw8fEhwcjJOTEwZKBQbpSZiXLK2zn56BIcZm5jyP08S/lUCLjj5s8t9A//792bVrF+Hh4QWuNvr168f5KyGM2nESY3MLqjdrQ3ZmBtsnf8bSTl4E7/uB0nYOGBibULKCHac2r6JiJTsqV65MaGgo7u7u/PDDD8TExMhfWI0aNUKlUnHmzBk++eQTnZIrQ0ND7t27x5dffsmlS5dQKBRyN8usXEknXJDyJAHT4qU4us6PZZ29CPi8O+nJSRxaMR8JqUBPSlZWFt26daNly5Z06tQp37i/v7/sNQDIycnhwYMHVK9enatXr7JixQq6devGkydP5H22bNlCXFwc8+fPZ9KkSTrns7KyIvzuAx0X9uyjN3H0qE1sikYcZ9SoUdjZ2aFQKLh27VoBf2nYtGkTCoVCJzkuMTGRjz/+GAcHB1xcXDh9+rQ8tnDhQpycnFAqlfkS6vr374+joyPu7u40aNBAzukAGD9+PD/88EOBc3gfPHnyBD09PR03eM2aNeXPRr9+/eQ2yGq1msDAQHr27KlzjqSkJPbv38+2bdu4desW0dHRhV7P3t6ejRs3smbNGpKTkwl+lolJIeWFWpRoPFRatCWKjRo1krd5e3tTtmzZfNcbPXo0hoaGrJw+nq0b1qOvVMieLgVQxVyf80smsHHN6nz5RiqViqdPnxIREVHo/bwNa2trBgwY8IePF/x9EMbBf4DZs2djY2Mj/+zatYvIyEhsbGwYO3Yshw8fxsbGhm+//RaAmTNnEhsbyzfffCMnyaWmpsrn0+YcBAUFsWLFCj799FPat2/Po0ePCDt+kCr1muabg5VjDaIuaFa3aqBt4/rs27cPfX19BgwYQOvWrfHx8QE04i82Nja8fv2atWvX4lS5Igm3wynvUJ3KnvWR1LnkZmej1NND1aYLiXdvk5b0Ap+5K7l2cDdXr1zm2LFjxMbGEhMTw7p16wgMDJTv4cyZM1y7do1+/fphY/NbrferV6/w9vamXbt2jB07ltDQUPbu3cvw4cMBMNRT6CR7GRibEH44iIe3rjEs4CCtRkzFsUEL7DzqgqRZoeclOzubbt26Ub58eb755pt879H9+/e5ePGizsOoYsWKKJVKOQfBw8ODypUrFxiC0SaH5TUcHienEZos6ZSVHtuwjJqd+/PD3VeEPkunS5cunD17Vl5Jv0lMTAzfffcd9erV09k+efJk6tWrR1RUFJs2baJnz55kZ2ti5t7e3hw8eJDGjRvnO1+nTp24desWYWFhTJkyRf67A0ycOJHZs2fn8/K8L9zc3GjYsCGVKlWiU6dO+Pn58fDhQ3nc1tYWKysrLl26xJEjR6hVqxYlSpTQOccPP/xAq1atsLKyonfv3mzcuLHIazo7O2NqasrNiNtymWFB5YVa8pYZgqZEsXbt2oBmdZ83eRU0xu7y5csBjXEbFRXFsGHDqONsj6m+gt6OxfncpSRj3Utxf+8GmjduWKA3BMDLy4tjx46969uZj1GjRhWa2Cj4ZyHCCv9StPFsreJZQRRWbvTdd9/l0y6ws7MDoGnTpnJiH2g0B9atW8eRI0dQKBQsXrgA11YN8rWDrlzTi5CfA6nXdQAfVzSja9fPMTMzw8LCAoB9+/bh4+ODq6ur7E7NqyQXdC+FB96fcO/KOUyLl6L30gBeJ71k16yRKBQKwo/8yN0rp8nNzODZs2eYm5szatQoDhw4wI0bN+jbt69cmXDq1ClGjBhBSkoKkiSxe/duli5dyooVK3BycmLbtm3s2LEDc3Nzdu7cSfny5QG4F3WHr9o0J/31a7IzM9DTNyDrdSoD1+zBxKI4d84fx9W7PZU96nL020V8vXQJAQEBKJVKXFxcSEtLo0yZMlhbW9OlSxdevnxJQkICDg4OBAQEsHHjRqpUqcLAgQN1xho3bszhw4f56KOP+Pzzz7l27RqjR4/GwcGBhQsXUr16dXx9fYmLi0OtVtO4cWMiIyOJS83mxq0IuvcZI/8dsjMzCD+ylzZjZgMaF3bvml6Fll+q1WoGDRrEypUrZVe7lp07d8qr5tq1a2Ntbc2pU6fw9vamTp06hX7u2rdvL/9er149Hj58SE5ODvr6+pQtW5YqVapw5MgRWrduXeg5/ihKpZI9e/Zw+/ZtTp06xcGDB1mwYAFXr16V9xkwYAD+/v68fPmSwYMH6xgPoPHuaENCAwYMoFWrVsybNw89Pb1Cryv9GmbSGmiFlRfK+6PxVBkoFcTHx8vhA5VKpePdUSgUnDlzRs49+eWXX3jw4IGOoJGBUkExAyU3btxgz549Oh6eNxFliAItwjgQvBMFJc8BDB8+XF5Z5yVvO2ifOatQAJ4qd7yLpeJRuoz8oH4b3bp1w8TERFMJkZ5N1uvXIGkedVXrNmbKoXDSU5Lw61CHhj2HoIi5Ln9Rrl69GoCxY8dy9+5d1q1bR40aNWjSpEm+L8AFCxZw+fJl0tLSKFasGAAdOnTQWfk6OTlxLSqG76M0OQyXg7ayb/EkTCyKk/byOQ8jwomPCOPgN7NJT01h6tSpdO7cmcDAQJo3b86JEydwc3Nj//79PHv2jD59+nD8+HGGDx/O5MmTOXToEM2bN+fgwYOEh4djZWXF8OHDefHiBX5+frK7dseOHXz66aeMGzeOZs2aUbZsWR4+fEh2djbHjx+nQYMGAOwPuY2kzqW8o4t8D/E3QylpXRFDE1PgNxd2YcbBsmXLaNCgQb6V5vPnz8nOztZJjrSzsyM2Nvad/q5avvnmG9q0aYO+/m9fRdrV659hHGhxdnbG2dmZIUOG8PHHH7Nv3z55rGPHjkyaNAkjIyNatGihIwV87do1wsPD+eyzz+RwwLNnzzh48CDt2rUr8FqRkZGkp6fjUr0aF+9nywaCtrxwSce6+YwDBcieJ1NTU7nM920cP36ckJAQ2ZiPj4+nTZs2rFu3jvj4eGJiYuQcm8ePHzN48GAePXrEsGHDAE1CrFA2FIAwDgTvkfbt2+d7OBQvUYL9R45pkuA8+hRyZMG8aZCEPktn9e6DWJQqQ9mq1eTtxSyKM/PEHVrZFsOjdP766mXLlsm/F9ZKZNq0aUybNu2tc7I1M6CVbTEOx6VhYmaOUTEzbh7/GUsrGzpN86Oiex1a2RZj26LpmJubM3v2bECT6Ojj40NYWBizZ8/mwYMHbNq0CYDBgwfTuXNn4uLimD17Nm3btpUfutqxe/fuUadOHZKTk5k3bx7z5s0jKysLT09PDhw4gK+vL1WrVpUNg2y1xI5N39G430idmHZy4iPMSpWRX7/pws7Lu6w0/z9s27aNnTt35ju/lZUVN27eIi1b/V6TJ7PVEjGx8STEPaBJo4YAvHz5kvv371OlShV5P2NjY5YvX46pqWk+F7m/vz/jxo1j8eLF8rY1a9bg7+9foHEQExPDwIEDGTZsGKWKW1I6K4q4DAXGFsUB3fJCLUo0UuPa+3Zzc2PXrl3vdI+LFi3SSXR9s4+D1ggAjRdwzJgxOpUYERERDBky5J2uJfh3I4wDwXsj7+rrjzJ06FAuXryYb/uFCxfwKG3C7N6fyB6JvD0ban/Ang0epU0oY6zPvpee7MxIJy3pBW4fdcAxzzy2vXHM27K3ixrXjkmSxMqVK2nZsmWB+5mZ/VYqmpUrYV7GCs8OvXT2MTQ2IefXLn1atC7sNzlz5kyRK019fX0eP34sGzIxMTFUrFix0PvI+6AaPXo069atw8rKirZt22JiYsKYMWOo06o9l+KT2LUzkNMh4SiVSoz0lHRo/wlfL17Axo0bWb58ORERESxZskRWryyK2FdZfNy8Ke1nr0YC1vT3Ie3FUwwMDFCgUfvs0KEDy5cvZ9GiRbJBB5pGRp9//jmgMfDWrFlD5cqVOXDgABMnTqR379507dqV8ePHM3nyZNatW0dKSgo7duzA0tISCwsLVCqVXEZbNv0pM4YOQcpVIyFRysZOLi/UogZql/3NyNWWKL548UJOpGzbtq3c7KhGjRo4ODhw8uTJt74XRZGWlsb169fx9vb+f51H8O9AGAeCvxVr164tctzGzAAbM4MPVpZ34MABpk6dmm/7lClTGN6tG+e6dCHlxlkGjB9EmZIWSJLEnj17sLe3Z/Xq1YwdOxYLCwvWrVun81A/cOAAT548oVy5cmzYsEHnC7mwsY4dO7J8+XIaNmyIqakpr1+/5v79+3I1RV4M9RQ07DE4nxiTlUN1nj7Qza5XADUc7OXYvxZ/f3+2b99O06ZN+fnnn+nRowcGBgb4+fkRFhZGx44dWbt2LbNnz6ZmzZqEh4czbtw40tLSqFy5ss6D+/jx4zx69IjOnTvz8uVLUlJSOHjwoPyeREZGsuaHPUTZJ3Pr12z5If4/ERN6icgzR7Dq9gWhz9KxtramVKlSmJqasnjxYvT09Pj888+5fv06I0aMIDExEX19ferUqcPq1auJSIV5X6/m4YP7+I/wQd/ACD09fbyHTKDZoHG0si3Gk6unqFWrFllZWZiamrJ582bc3d25evUqDRo0oHPnzjRp0oRjx47x/PlzLC0tiYuLw8PDAy8vL6pUqcLBgwcZNmwY8fHx6Ovr06BBA+bMmSNrE3h6ehIVFcUnTetjc/ZyvpwcQH7dyraYjqGrLVH09/dnwoQJAOzfvz/f37wgCgsHAvmMia1bt+Lr66tjZAr+u4i0UsE/Em2S1Z9dr9+mTRsd9ULtT7du3QAI2LSRmh4qGnrVo0aNGlSvXp0jR47Qq1cv+vfvj5eXF66urqSkpOi4exs1akTPnj1xdnbmwYMHOk2hChubNGkStWvXpm7duri5uVGvXr1CSw8NlApZKS8vJStUwqxkGZ7cvQ1ovgCOfTWB+Ph4cnJyaN68OVWrVtU55tChQwwZMgQnJydWr17NnTt3MDAw4O7du5w/fx4HBwciIyOZNWsWYWFhREdHU7FiRdq3b8+5c+cYNGgQPXr0oGTJkgQFBZGUlIRSqWTQoEFy1n2msSVWHQcjSRJRl38LMxxeNZ8mvypQHopNZeKUqYwYMYLOnTszefJkunbtChSsQDl13kKOxKcRemA3jfqOZNyPFxm98xSGpmbcOnUIgL03H9KjZy82b95MeHg4fn5+cmWIv78/Xbp0YcaMGQC0aNFCjsdrqxri4uIACAwMpE+fPhQrVgwjIyMGDBjA9u3b5fvo2rWrLDnuUdqE3g6WOFga6pQZOlga0tvBssDQ2OjRo//0h7ZSqdTRUhD8x5EEAsEHZdasWdLo0aN/99jvJfZVlrQo5Gm+n55fbpDq+fSXX8e9ypIqVaokBQQESBUqVJDS0tIkSZIkT09P6cSJE1KDBg2k1atX65w7MzNTqlChgnTs2DFJkiSpSZMm0o8//qizz5o1a6RatWrJrytVqiRdunRJAqSBAwdKs2bNksf23E2Wvgx5Kvmu3CGpWneRAKlEhUqSgbGpVN6xhjRs8yFp0JrdkpNHHUmSJKlfv37S8uXLC713Pz8/qWnnntLCSwmSvqGRNPvsffl+K3vWl/QNjSSrqtUlO1VdqXR5G51jzc3NpXPnzkmWlpZSeHi45OzsLN26dUtnn19++UWytraWUlNTJUmSpHbt2kk//PCDPL5//36pUaNG8utTp05Jnp6e+eaZlauWUrNypcvBIZK7u3u+n2XLlhV6jwLBn4nwHAgE/DtbL2uTJwFNV8xfcf2oA+UqO6JWq3Vc2O7u7jRr1kyumdcSEhKCl5eXzjZDQ0M8PT0JDg4u9Pp169bl5s2bBY7t27dPTuBr2qwZw1vVw69TPTJTU2g9RtMPwq1VJ+r5aBp4VXT15PG9SJQWJenarTv79u3D39+fe/fu5Tt3Wloa323YgE39lrxKeo5CqSdLd6tzc8nJyqTliKmM3nmKOp/249njhxw68os8r1evXrFjxw4cHR1xdXXNV/t//fp1+vfvT2BgoFzZ8jYKKxHUesBq1/Qo0EP1xRdfvNP5BYL3jcg5EPyniUvN5kpiuiyLrHXv1vkTExzzJrz9nrF3JTExUSe/IVstkZKRhV3dZrQdOxcF0G/I8AKTOOfNm0edOnUYOnTo/3seUgGVIVlZWRgYGNCxY0dq1aoFwP4jx5h75BorujfDrdVvqpGvEh9TroqT/Fqdm8vdK2fYfO4CpibGpKWl0bVrVx2NAq0CZXPvj6jUvC0Zr1LIzc6U5/K/RRMxL12OBr009+fR1ofDq+YzedIkpk2ZjJeXF9WrV+fEiROMHDkS0H2w37p1i3bt2rFx40YaNmwoX7dixYo8ePBAfv1mcqboVCj4pyE8B4K/hJycHObMmSO3MFapVAwePJikpCQSExPp378/9vb2eHh4ULNmTTnuHhAQkK8JDhTdEhk0nRjd3d1xdHSkefPmPHz4kJCn6XwflayjHigB0clZbItKJvDkJTmh7G1tlYtqnXzgwAFq1qyJSqXCxcVFlufNy/Hjx9HT05M1+eGPSwmXLVtWXnn+dPYK8/aeYcSO07QdOxeQqGJhUGh1h52dHT179pQbVoFGXvjChQs6+2VlZREcHEzNmjULnceVK1dwcflNY0GSJEaMGEHr1q05e/Yst29r8h4M9RRkp7/Od7yBsTHZWb9VVhS3qoC1kysqN805a9euTUhIiKzK+KYCpQIwNrfAokx5nsfd56evppD05CFtvpgjlyjGhl8lOzODo8ePExwczNKlS4mLi+PevXv06NED+O3BHhERQZs2bVi/fj0fffSRzlx9fHzYunUraWlpZGZmsnHjRrp37y6Pi06Fgn8cf3FYQ/AfpW/fvlK7du2kFy9eSJIkSWq1Wtq5c6d048YNydnZWZo1a5aUk5MjSZIkpaWlSV9//bUkSZK0adMmqUOHDvnOd+fOHSksLEySJEnKycmRunbtKse0c3NzpSpVqkjHjx+XJEkTj27TsXOB8fi8P44NWki7Dx0vcP4jRoyQRo4cKb9++fKl/HtQUJDk5uYm31eJEiWksLAwqXXr1tLs2bMlIyMjKSUlRd6/YsWKkomJiWRhYSGZmZlJpUuXltzd3aXq1atLVlZW0owZMyRAOn36tHzMypUrpX79+hX5Hgcnvpb6fv29VPfTftKikKfShJ+uStbOblJ5xxpSuSrOkvcnneT3v1KlSlJoaKgkSZLUrVs3CZCsrKykEydOSPv375esrKyk1q1bSw4ODlK1atWkmjVrSg0aNJDUarW0ZcsWqVixYpKNra3UpFlzKfp+jHT69GnJyspKcnZ2lu7duye9evVKMjIykoYOHSpJkiRt27ZN8vT0lKpWrSp5eXlJLvUaSd3nr5Hfe0D6ZNIiSdW6i7xt3rkYyaJkKcnKykoyNTWVTE1NJX19fSkkJETKzs6WOnfuLA0YMEBSq9WSJP2Wx9Cw9zCpsmd9ybF+c2nexXipSp3GUrmq1aTyjjWkiq61pPGrNsvv2bRp0yRHR0epb9++8raPP/5Y2rUnSGrWooVUvHhxnZyAQ4cOyfvNmTNHqly5slS5cmVp8uTJOn8LX19faevWrUX+vQSCvxMirCD44ERHR7Nr1y5iY2Nl3XqFQoGPjw/+/v464kGgUYgbPXp0kefM21lR2xL5xo0bAAQHB6Ovr0+zZs0AGDJkCFOnTaf+pAz0jIwLPF/So3gS70aidMivQa9tq6zthAhFt07WttUdOHAg06dPp1SpUnLTm4uXr/DkyRO2fv89+3/6icePH+Ps7Cx7EFq3bs3du3exs7Nj0qRJnD9/vsj3QUtcajZH4tM4vGo+/b7+HgCLMlYM3fgzBsYa9/ZPflMZP20m/t+ulI8LCgrC3Nwc0OgagKZio1KlSoSHh1OsWDEyMjKoWbMmq1evJjIyknHjJ1DBsQZPnzwmLOIO1apVw7lmHRatWENxA017bycnJ3Jzc7lw4YIsyOPj4yMLT8WlZsvKkwCLQp6S/PQRv3y7mKWdvFDq6aFnYIBDVQdeJb3A1NSUe/fuMWLECDw8PPj+++8JCgrCwMBAzoNwr+OFfd9JXNy5kZysTEpXqsq3fVsBYF66HLnZWSREXmfDjC/4aeVCcnJy8PLyws/Pj/nz51O9enWycyXiH8ZRd+pqWvrtoBWFh51q1qxJQkICa9euJTU1lVatWhEcHEx2djaVKlVi3bp18r5+fn5s3rwZtVqNk5MTmzZtonjx4iQkJNC/f39iYmIwMjLCwcGBtWvXUqaMRriqUaNGbNmyhcqVK7/T50Ag+KOIsILggxMSEoKDgwOlS5fONxYcHJwv+e33om2J3KFDB0DT1S5vUyHjYmYYFjMn+enjQs9xL/g8NjVUBaoHvtlWWUvfvn2xtbVlxowZbN26FdAYBoGBgXTu3JmxY8fKJX9PshQE3Uuh75hJWFaw4559Ex68yiYjR61zTi8vL+7fv0/79u3Jzs7mxx9/fKf34EpiOg9CLvDswV3SXyWxa9ZILu7aJBsG6txcstNfc/biZVQqFcWLF6d37974+PjIhstPP/1E69atqVatGiEhIVSoUIHNmzdz7949tm3bhqWlJfvOh2BpX42B/vuZ+HMwn28/Tk5mBjn6xlxKM8K6rkYO2tbWFmdnZ3JycsjJyWHv3r1MmzaNFStW4OLiQhuvmvj3bkbo/l3yl9L34weQkZpCdkY6evr6VChdksUL5jF37lwGDRqEiYkJO3fu5NmzZ/Tq1Yvr169jbW0th1Q2r19D7pUD2LrUxNDElL7LtzJqx0lG7ThJr0XraTl8Cl+tC6BSRVtu375NdHQ0W7duxdbWlh07drDtVDDVOvbFyMySm8c1ugJ5w06hz9J13vO8bZUNDAyYNGkSR48eRa1Ws3btWgwNDQFN/4NNmzZx4cIFbt26haenp2wk6enpMWPGDCIjIwkPD8fe3l7WNgAYN24cs2bNeqfPgEDw/0F4DgT/Kt7WEhngdWY2Wemv8R/WBQNjE5R6etjUqEm9rv1Z1csbq6rVePUskZzsLPbM+4JOSxfgWFmTXObr68v58+d1BH5mz55NUlISW7Zs4cKFC3Tr1o0GDRpga2tL/fr1iYyMJCgoiMaNG9OrVy9Gj/mCuKpNyE5PI/rSKYZuOsC5HRuIunUD0xKlKP86m7Fjx3Lo0CFSUlJ4+fIljo6OLF68mJEjR6JUKpk3bx7p6emkpKQQEBCAhYUF9+/fp0uXLuTk5vIkVZOEp2dgKM/zyd1Ilnaqx8uEOCRJjW0ND/qv2MFAB1M6d2hP+fLliY2NpX///nJfCicnJ+bOncuiRYtQKpU0a9aMRo0a8eWXX1LawYXEUlVIuB3Okwd3KVOpCqEHdiFJEq+eJ1LJvTbHH2dhXbESU6dO5fLly1hbW/Pq1Su5SVGNGjU4d+6cLCzkrvKgaQMv7qVkkhARTtXajWjbrTfjB/vqrNS1Aj7t2rVj3rx53L9/n8jISBISEmSjrUSJEmRkZDB76hRWrV3Hg2sXKWNXFQXgXrEcg2rZEX31XL7Ph4eHh8bzEpWMvoERTg28eZkQJ49rzbfDcWmUMdbHxsxAbn6kNUKNjIxo3rw5MTEx6OnpUb9+ffn4sLAwGjZsKHto2rRpQ9OmTVm9ejXlypWTmyyBpuIjbxOltm3b8tlnn5GcnCx6IAj+VITnQPDBqVmzJlFRUTx//jzfmKenZ4Hyye9CYS2R38wkHzLAl+zMdIZs/Jkxu87w+fYTONRrgnExc4xMzRi14yRNB4ymetOPMS9dDu8mDUlO1ri8U1NTiYmJ0WmrnBd3d3fu3r1LdnY2J0+eJDo6moiICLmB04AvJpKVlUnczVDOB25EoVTyw6SB7F86ncSYKO6HXODIwQOcOHOWsLAwJk6ciIWFBefPn6dFixaUL1+ePn368Nlnn9G5c2esra2ZN28eANbW1pw9e5bzV0IYs+sMCoWC3OwsAHJzcgg/8iN9lm1l/qWH1O7Ym8zXaVzcs5kSpctiYWFBbGws9vb2+Zos5eTkcPnyZT777DOUSiVffPEF7dq148LDFMpWrELHqX7smjGCVb28eZ30Ej0DA5waaFQdlcCjJ09p0qQJ1tbWAJibm2Nqqmn8lJmZSZMmTVCpVHzyySekv05j6WddyDj+A1ZWZalmVYKvx35WYPJk8eLFMTMzY/v27XzzzTfs2bNHx3OwevVq4uLi6NWxLdM/H8LDX3bKrYs72VsUWY1yJTEdJVCtSStunTqIc+P8ktXaplWgMVbq1q1b6Pny4unpydGjR3n8+DGSJPH999/z6tUrXrx4obNfbm4uq1atkj1goPFIuLq6cubMmXe6lkDwRxHGgeCDU7VqVT799FMGDhxIUlISgCw77OXlRVJSEvPmzSM3NxeA9PR0VqxYUeQ5c3Jy6N69OyVLlmT9+vU6MX9PT0+ys7M5ceIE0dHRBO3ZjWezlhQvo+kJoFAocP2oA4o8TXasHGrwIu4+IyfPpEKFCmzbpumWEBUVhZubm06OQUZGBqmpqYAmP2L//v2UKlUKMzMzFAoFKSkpRPwqCXw7RbPuTH4cT0LkdTpO9aPl8Km4teqM60ftqVzTi7KVHUlKyyAjI4Nbt25hbGwsq+O1atWKrKwsudX18OHDZSU+IyMjTExMMNRTIOXm6kgnpyQ+wqJsecpW1uRmeHUfxKtnTwg9sAtDPQV6enpEREQQGxsrd/TTVnxUrFiRChUqEBcXR/fu3WndujVZWVlcuX0XNeDq3Z7hWw4x8vuj1PPxJTc7G6dGmmx+NfAqOYnklBSaNGmCh4cHM2bMkP+2eRUolyxZQsmSJQkLC6NRgwYogPPnzqJSqahZsyZ2dnY4OTnRv39/+b3WenGmT5+e7zPh7+9P37590dPTo02bNsTcv09sdORbVTWz1RJRyVm8Tn3F5jG9adzvc2yqq/Ltl7dpVd62ym+jWbNmjB8/nnbt2lGvXj05nyBvZ0pJkhg+fDglSpTIl28j2ioLPgQirCD4S9i4cSPz58+nbt266Ovro1arady4MS1atODUqVNMnjyZqlWryg/YvCv1w4cPY2NjI7/u2rUrnp6eBAUF4ebmhoeHBwANGjRg9erVKJVKtm3bxpAhQ3j69CmGhoasXv0tJ9LzTUvGTlWXpCePqKqfTp06dbh58yZqtZro6GhMTEx08g0ePnyInp4erq6uKJVKzMzMMDU1pUyZMrRt25YNGzbQtWtXFEolia+z8fykO5eDtvI87h59lm3mZ79p2LrU5GHENQBKVKiE0sYOKysrMjMzKVWqlNy+WF9fHxsbG9asWUOTJk2ws7Pj0aNH5OTkoK+vT1ZWFnXq1CH6fgwmJUqj/NV9n5X+GkNjU82/JqZYWlUgLekFHg2aYqBU8O2331K1alW53a9CoWDjxo34+PgwaNAgHj16xLJly7h69SqXL19GLUlYWlUAIOXpYyzKWKHOzeXgirkolEpKWNvK7092ZgYvXr7k2C+/oFarad++PWvWrJF1BCC/sJCHhwfPnz8nKiqKChUqEBERQcuWLenatSvXr18HNKvo+Ph4xowZg6OjIx9//PFv18zOZuvWrRgYGMjloK9fv8bf358lS5YU+dnMypXISEtl08huVG/6MY16Dyt0X23Tqt/TVhl0W51fvHgRGxsb2eADGDVqFHFxcezduzdfZ0ihmSD4EAjjQPCXYGBgwJw5c5gzZ06B4wEBAQVu9/X1xdfXt8AxrSZ+QXh5eREeHs7OnTtZsGABdZ3tMXyWXmgDHAwM6Dd4KIcCt8gCOkqlEh8fH1QqVYE5B3k1CkATgujduzcGBgZcv36dtGw1K2+8IDMtlYUta+DWsiNGpmYkP0nAsX5zfOas4ujar0iMieJ10gvW+2/iwE//IyYmhuPHj8vnrV27Nnv27CnwPg0NDbl27Rp3X6Th03cAz2Pvoc7V3F1WxmvW9NMYGercHJBgxa9z3rp1K8bGxvkecE5OTly7do1Lly7xySef4OrqSvXq1dm5azdXDY2QgD1zRpP0KJ6c7CycGnpjVMxc7vz4MiEWpZ4+vr6+8gOtc+fOXLhwQTYOChIWcnBwoGPHjnz++eds3LiRatWq0aZNGx3FRbVajYmJCaampsyYMYOZM2fKY/v27cPe3l4nRBUREUHTpk1ZtGgRBgaFhxSy0tPYNLIrjvWb03zQuEL3A41olqGeAjc3Nx0Vxbfx6NEjypcvz+vXr5k5cyYTJ06Ux0aNGkV0dDR79+6VkxjzEhERoXOvAsGfgQgrCP5T5M13KKgBDvzWAOerqeMxMzPLJ+bzrpiZmdG9e3e+/15TSmiop0ABGBUzY865B3w6S5MXYWBiSvavD1PvoRMpVrwkVWs3BEmNn58f69ev59WrV4Amf+Lly5dkZWUREBBATEwM5cuX13FJA1QpWYzRIzUr03tXTmNooonxj955ii92nqKn30bKli+PRxUb1Go1mzZtQl9fX36AS5Kk0+inbt26xMTEULJkSaZNm0aLZk3lxk79VwXyxZ5zTNh3hfYTF1HeoTrPfu38eHl3AI3bd+H4r1n7OTk5HDlyRBYEKkpYaMGCBbi6ulK3bl2cnJzYsmULiYmJTJo0CdCsoLXnGThwoM6D1N/fP5+xWK1aNSpUqMBPP/3E69evsbGxwcfHh1u3bmFjYyNXGny7cgXxN0O5efxnVnRvyoruTTmxYVm+v68ScLQ0xECpoF27dpw7d04OlwC4ubnh5eVFSkoKNjY29OnTRx5r2bIlNWrUwN3dnYYNG8qG0rlz51i5ciUxMTHUrVsXlUqlk1gbExNDbm6uEFQS/OkIz4HgP0XefIdx48bx+eefI0kSycnJGBubkPU6lZj/+dPpiy/IysoiMTGR+Pj4Ir0SeYmOjqZSpUoYGBiQlZXFjz/+iJubG/Bbp8To5CwdT4VV1d8epgClbOyIu3gMn2WzMDQ0ZOvWrbJx8vHHHzNixAhu376Ns7Mz3377razE9+DBA8qUKYOpqSlqtZrwX/ZhbGxCCT0JyzLluR9ygQXe1TE0NCDjVTLNf9V9OHr0KJIkYWBggK2tLYVhamrKggULmD17Nh07dqR2WRPuJGfl28/F+xPunD9B1bpNMCtjxcqpX7Jq/gxq1KiBnp4ejRo1kuPoo0aNIjk5mUmTJskP/S+//JJWrVrx3Xff8b///Q8TExPUajVLly6VXfEAzZs3p0WLFoAm3BIZGSmPHThwoMB7CAkJkX8vLG4/bdo0+o6eqKO7UBBqoHZZjTFVpkwZ2rRpQ1BQED4+PgCEh4cXeqw2NPImDRo0KFB2WsvatWuZOHGiTk6NQPBnoJCK+iQKBP9CsrOzmT9/Pjt27NDJdxg2bBienp64urqSk5NDdnY2jRo1YtasWfJD09fXt8iwwvr161mxYgV6enrk5OTQokULvvrqK4yNNWJLb4r9ADyOusXuOaMZuU3T/CcnK5Nba2YSeuk8BgYGWFlZsXbtWuzt7QGNy3zixInk5ORQpkwZUlNT0dPTIzk5WRYuKl26tNxEqVSpUmSrJX7c+z9mTJ1Mbk6OLOOsLYfbvHkzZ86ckdsKvyuhBYRmMl+nsta3LcM2H+ATx7IFtiD+//Ls2TOaN2/O1atXC3S9vw8KujdAft3KtpjOvT1//pyDBw/Su3fvP2U+ACtWrJDLWQWCPxNhHAgEH5iCHjoBo3rw0ZCJVKjhke+h8yFo1KgR69evp1q1ar/72Phfm1fdydO8KuPGeRo42eJdx+O9zxU0vTJyc3N19AP+DPLeW8TZXziyagFGekpM9RVy1cOUKVPo1q3bnzoPgeBDI4wDgeAv4M0H6ou4+xgk3mdY905/WjfIwnjy5AnHjh0rVLuhIIYOHZpPj0ICjp0+h6WZ6VvLBf9pZKslsnIlDPUU/7p7EwgKQhgHAsEHYMOGDTpKd1qWf7OCOvUbioeOQCD4WyGMA4FAIBAIBDqIrBaBQCAQCAQ6CONAIBAIBAKBDsI4EAgEAoFAoIMwDgQCgUAgEOggjAOBQCAQCAQ6CONAIBAIBAKBDsI4EAgEAoFAoIMwDgQCgUAgEOggjAOBQCAQCAQ6CONAIBAIBAKBDsI4EAgEAoFAoIMwDgQCgUAgEOggjAOBQCAQCAQ6CONAIBAIBAKBDsI4EAgEAoFAoIMwDgQCgUAgEOggjAOBQCAQCAQ6CONAIBAIBAKBDsI4EAgEAoFAoIMwDgQCgUAgEOggjAOBQCAQCAQ6CONAIBAIBAKBDsI4EAgEAoFAoIMwDgQCgUAgEOggjAOBQCAQCAQ6CONAIBAIBAKBDsI4EAgEAoFAoIMwDgQCgUAgEOggjAOBQCAQCAQ6CONAIBAIBAKBDsI4EAgEAoFAoIMwDgQCgUAgEOjwf24dwaMT5FVnAAAAAElFTkSuQmCC", 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", "text/plain": [ "
" ] @@ -141,7 +173,7 @@ }, { "cell_type": "code", - "execution_count": 25, + "execution_count": 6, "id": "0273b3be-d420-4a2b-b1ca-de0a3e05e8e6", "metadata": {}, "outputs": [], @@ -153,7 +185,7 @@ }, { "cell_type": "code", - "execution_count": 26, + "execution_count": 7, "id": "d9c7affa-2558-433d-a3b1-b5dcf31b7ccd", "metadata": {}, "outputs": [], @@ -183,7 +215,7 @@ }, { "cell_type": "code", - "execution_count": 29, + "execution_count": 9, "id": "82220b36-281a-4724-88dc-6c4d6fdbf4dd", "metadata": {}, "outputs": [], @@ -197,7 +229,7 @@ }, { "cell_type": "code", - "execution_count": 30, + "execution_count": 10, "id": "b2084229-ae6e-40a0-a966-919d77cb5ef4", "metadata": {}, "outputs": [ @@ -681,7 +713,7 @@ "43 [[-0.46518034, 0.22024783, 0.28029412, -0.2428... " ] }, - "execution_count": 30, + "execution_count": 10, "metadata": {}, "output_type": "execute_result" } @@ -708,7 +740,7 @@ }, { "cell_type": "code", - "execution_count": 31, + "execution_count": 11, "id": "e6c0fe91-e158-4fb3-aa91-d96e54ec5f88", "metadata": { "scrolled": true @@ -4181,7 +4213,7 @@ }, { "cell_type": "code", - "execution_count": 32, + "execution_count": 12, "id": "4c61048d-ca2e-407f-b72c-828852e7302f", "metadata": { "scrolled": true @@ -7622,6 +7654,8 @@ ], "source": [ "proportions = [0.5, 0.15] # example proportions for hops 1 and 2\n", + "neighbor_weight = 0\n", + "\n", "total_len = len(nodes_list)\n", "\n", "# Loop through all nodes\n", @@ -7656,7 +7690,7 @@ "\n", " # Normalize the final embedding by the total weight\n", " neighbor_embedding = neighbor_embedding / weight\n", - " node['FINAL_embedding'] = (embedding + neighbor_embedding * .25) / (1 + 0.25)\n", + " node['FINAL_embedding'] = (embedding + neighbor_embedding * neighbor_weight) / (1 + neighbor_weight)\n", " #print(f\"Final embedding for node {node_name}: {node['FINAL_embedding']}\")\n" ] }, @@ -7670,7 +7704,7 @@ }, { "cell_type": "code", - "execution_count": 33, + "execution_count": 13, "id": "1b522cd8-4e38-4148-94b1-de3386762a70", "metadata": {}, "outputs": [], @@ -7695,7 +7729,7 @@ }, { "cell_type": "code", - "execution_count": 34, + "execution_count": 14, "id": "143fede2-c942-4eac-a544-277f88b20479", "metadata": { "scrolled": true @@ -7712,7 +7746,7 @@ }, { "cell_type": "code", - "execution_count": 35, + "execution_count": 15, "id": "27bee18b-e76b-43f1-9bcd-7866ffc9d394", "metadata": {}, "outputs": [ @@ -7767,7 +7801,7 @@ " sR_IL6_sgp130\n", " Based on the provided context, 'sR_IL6_sgp130'...\n", " [[-0.41926485, 0.05604683, 0.31495243, -0.0975...\n", - " IRAK2 mediated activation of TAK1 complex upon...\n", + " Interleukin-6 signaling_(128814)\n", " \n", " \n", " 3\n", @@ -7783,7 +7817,7 @@ " sR\n", " From the provided documents, there is no speci...\n", " [[-0.24422143, 0.22741008, 0.3196285, -0.20558...\n", - " Regulation of Complement cascade_(127866)\n", + " G alpha (12/13) signalling events_(128349)\n", " \n", " \n", " 5\n", @@ -7823,7 +7857,7 @@ " CRP Suppression (%)\n", " Based on the context provided, \"CRP Suppressio...\n", " [[-0.47315472, 0.18459623, 0.24418907, -0.1895...\n", - " Cannabidiol_(14656)\n", + " Immunoregulatory interactions between a Lympho...\n", " \n", " \n", " 10\n", @@ -7839,7 +7873,7 @@ " gp130\n", " Gp130 is an important protein involved in the ...\n", " [[-0.35777402, 0.12645116, 0.3562525, -0.23347...\n", - " Interleukin-12 signaling_(62987)\n", + " Interleukin-6 signaling_(128814)\n", " \n", " \n", " 12\n", @@ -7847,7 +7881,7 @@ " R_IL6_gp130\n", " The species named 'R_IL6_gp130', provided with...\n", " [[-0.3070841, 0.14377351, 0.28311783, -0.18864...\n", - " CD209 (DC-SIGN) signaling_(128715)\n", + " CLEC7A (Dectin-1) signaling_(62768)\n", " \n", " \n", " 13\n", @@ -7855,7 +7889,7 @@ " sR_IL6\n", " The species referred to as 'sR_IL6' in the pro...\n", " [[-0.41398245, 0.14713271, 0.3669848, -0.26080...\n", - " Interleukin-2 signaling_(128499)\n", + " Interleukin-6 signaling_(128814)\n", " \n", " \n", " 14\n", @@ -7871,7 +7905,7 @@ " IL6\n", " IL-6 (Interleukin-6) is a cytokine, a type of ...\n", " [[-0.4627117, 0.097201906, 0.3234311, -0.21945...\n", - " Zanubrutinib_(15748)\n", + " Interleukin-6 signaling_(128814)\n", " \n", " \n", " 16\n", @@ -7887,7 +7921,7 @@ " Ractive\n", " The provided context does not specifically men...\n", " [[-0.24638735, 0.19071835, 0.17823611, -0.2357...\n", - " Cannabidiol_(14656)\n", + " The NLRP3 inflammasome_(128804)\n", " \n", " \n", " 18\n", @@ -7911,7 +7945,7 @@ " CRP\n", " C-reactive protein (CRP) is a well-known marke...\n", " [[-0.4524013, 0.21426782, 0.26746103, -0.18231...\n", - " Cytoprotection by HMOX1_(63064)\n", + " Regulation of Complement cascade_(127866)\n", " \n", " \n", " 21\n", @@ -7919,7 +7953,7 @@ " sR\n", " The provided context primarily discusses the i...\n", " [[-0.25064346, 0.32432884, 0.2525344, -0.19168...\n", - " Interleukin-2 signaling_(128499)\n", + " Immunoregulatory interactions between a Lympho...\n", " \n", " \n", " 22\n", @@ -7935,7 +7969,7 @@ " sgp130\n", " Based on the provided context, sgp130 appears ...\n", " [[-0.37740308, 0.07933396, 0.32603347, -0.1108...\n", - " Interleukin-2 signaling_(128499)\n", + " Interleukin-6 signaling_(128814)\n", " \n", " \n", " 24\n", @@ -7951,7 +7985,7 @@ " Ab_sR\n", " Based on the provided context, there is no dir...\n", " [[-0.23842902, 0.18786879, 0.2620399, -0.21784...\n", - " CD209 (DC-SIGN) signaling_(128715)\n", + " CLEC7A (Dectin-1) signaling_(62768)\n", " \n", " \n", " 26\n", @@ -7975,7 +8009,7 @@ " Ab_sR_IL6\n", " Based on the context provided, there is no exp...\n", " [[-0.3548704, 0.1917099, 0.28657728, -0.262703...\n", - " IRAK2 mediated activation of TAK1 complex upon...\n", + " Interleukin-2 signaling_(128499)\n", " \n", " \n", " 29\n", @@ -8031,7 +8065,7 @@ " geneProduct\n", " The context provided does not specifically men...\n", " [[-0.30782086, 0.2336929, 0.23015884, -0.16083...\n", - " Interleukin-1 processing_(128470)\n", + " Immunoregulatory interactions between a Lympho...\n", " \n", " \n", " 36\n", @@ -8047,7 +8081,7 @@ " IL6\n", " Based on the provided context, here is the bac...\n", " [[-0.4397936, 0.15727538, 0.35291147, -0.22082...\n", - " Zanubrutinib_(15748)\n", + " Interleukin-6 signaling_(128814)\n", " \n", " \n", " 38\n", @@ -8071,7 +8105,7 @@ " Ab\n", " Based on the provided context, there is no dir...\n", " [[-0.37095174, 0.32116163, 0.20662963, -0.2790...\n", - " Canakinumab_(18416)\n", + " Interleukin-2 signaling_(128499)\n", " \n", " \n", " 41\n", @@ -8079,7 +8113,7 @@ " Ab_sR\n", " The provided context does not include specific...\n", " [[-0.15027289, 0.31890064, 0.17519885, -0.2029...\n", - " Regulation of Complement cascade_(127866)\n", + " Immunoregulatory interactions between a Lympho...\n", " \n", " \n", " 42\n", @@ -8095,7 +8129,7 @@ " Ab\n", " The provided documents include information tha...\n", " [[-0.46518034, 0.22024783, 0.28029412, -0.2428...\n", - " Sarilumab_(15662)\n", + " Interleukin-2 signaling_(128499)\n", " \n", " \n", "\n", @@ -8243,51 +8277,51 @@ " best_node \n", "0 CLEC7A (Dectin-1) signaling_(62768) \n", "1 Interleukin-2 signaling_(128499) \n", - "2 IRAK2 mediated activation of TAK1 complex upon... \n", + "2 Interleukin-6 signaling_(128814) \n", "3 Immunoregulatory interactions between a Lympho... \n", - "4 Regulation of Complement cascade_(127866) \n", + "4 G alpha (12/13) signalling events_(128349) \n", "5 Interleukin-6 signaling_(128814) \n", "6 Interleukin-2 signaling_(128499) \n", "7 Cytoprotection by HMOX1_(63064) \n", "8 Interleukin-2 signaling_(128499) \n", - "9 Cannabidiol_(14656) \n", + "9 Immunoregulatory interactions between a Lympho... \n", "10 Tezacaftor_(15045) \n", - "11 Interleukin-12 signaling_(62987) \n", - "12 CD209 (DC-SIGN) signaling_(128715) \n", - "13 Interleukin-2 signaling_(128499) \n", + "11 Interleukin-6 signaling_(128814) \n", + "12 CLEC7A (Dectin-1) signaling_(62768) \n", + "13 Interleukin-6 signaling_(128814) \n", "14 Interleukin-2 signaling_(128499) \n", - "15 Zanubrutinib_(15748) \n", + "15 Interleukin-6 signaling_(128814) \n", "16 CLEC7A (Dectin-1) signaling_(62768) \n", - "17 Cannabidiol_(14656) \n", + "17 The NLRP3 inflammasome_(128804) \n", "18 MyD88:MAL(TIRAP) cascade initiated on plasma m... \n", "19 NOD1/2 Signaling Pathway_(127908) \n", - "20 Cytoprotection by HMOX1_(63064) \n", - "21 Interleukin-2 signaling_(128499) \n", + "20 Regulation of Complement cascade_(127866) \n", + "21 Immunoregulatory interactions between a Lympho... \n", "22 Immunoregulatory interactions between a Lympho... \n", - "23 Interleukin-2 signaling_(128499) \n", + "23 Interleukin-6 signaling_(128814) \n", "24 Interleukin-2 signaling_(128499) \n", - "25 CD209 (DC-SIGN) signaling_(128715) \n", + "25 CLEC7A (Dectin-1) signaling_(62768) \n", "26 Cytoprotection by HMOX1_(63064) \n", "27 Immunoregulatory interactions between a Lympho... \n", - "28 IRAK2 mediated activation of TAK1 complex upon... \n", + "28 Interleukin-2 signaling_(128499) \n", "29 Interleukin-2 signaling_(128499) \n", "30 Interleukin-6 signaling_(128814) \n", "31 Interleukin-6 signaling_(128814) \n", "32 Regulation of TLR by endogenous ligand_(127918) \n", "33 Growth hormone receptor signaling_(127694) \n", "34 Signaling by MST1_(129128) \n", - "35 Interleukin-1 processing_(128470) \n", + "35 Immunoregulatory interactions between a Lympho... \n", "36 Interleukin-2 signaling_(128499) \n", - "37 Zanubrutinib_(15748) \n", + "37 Interleukin-6 signaling_(128814) \n", "38 Cytoprotection by HMOX1_(63064) \n", "39 Interleukin-6 signaling_(128814) \n", - "40 Canakinumab_(18416) \n", - "41 Regulation of Complement cascade_(127866) \n", + "40 Interleukin-2 signaling_(128499) \n", + "41 Immunoregulatory interactions between a Lympho... \n", "42 Interleukin-2 signaling_(128499) \n", - "43 Sarilumab_(15662) " + "43 Interleukin-2 signaling_(128499) " ] }, - "execution_count": 35, + "execution_count": 15, "metadata": {}, "output_type": "execute_result" } @@ -8306,7 +8340,7 @@ }, { "cell_type": "code", - "execution_count": 15, + "execution_count": 18, "id": "98e737b2-b175-463b-9506-d4294c4138ce", "metadata": {}, "outputs": [ @@ -8335,55 +8369,686 @@ }, { "cell_type": "code", - "execution_count": 16, - "id": "96db0b07-74df-4ff6-b851-a6f273d828ae", + "execution_count": 19, + "id": "1df9bdee-b9ac-4aa6-a2df-16580930a547", "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "R-HSA-9707564\n" - ] - } - ], + "outputs": [], "source": [ - "relevant_node_name = G.nodes[best_node]['name'].lower()\n", - "query_str = f'node_name_lower.eq(\"{relevant_node_name}\")'\n", - "\n", - "# Get the nodes related to IBD\n", - "nodes_df = primekg_nodes.copy()\n", - "nodes_df[\"node_name_lower\"] = nodes_df.node_name.apply(lambda x: x.lower())\n", - "nodes_df = nodes_df.query(query_str, engine='python')\n", - "\n", - "code = nodes_df.iloc[0]['node_id']\n", - "\n", - "print(code)" + "def fetch_code_in_graph(best_node, G):\n", + " relevant_node_name = G.nodes[best_node]['name'].lower()\n", + " query_str = f'node_name_lower.eq(\"{relevant_node_name}\")'\n", + " \n", + " # Get the nodes related to IBD\n", + " nodes_df = primekg_nodes.copy()\n", + " nodes_df[\"node_name_lower\"] = nodes_df.node_name.apply(lambda x: x.lower())\n", + " nodes_df = nodes_df.query(query_str, engine='python')\n", + " \n", + " code = nodes_df.iloc[0]['node_id']\n", + " \n", + " return code" ] }, { "cell_type": "code", - "execution_count": 39, - "id": "66b3300b-d0c5-439d-8afd-1909892b37be", + "execution_count": 21, + "id": "d2ab74b6-6fe2-41c8-8ca3-a2d543ba9dd5", "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "Nodes starting with 'ST': ['STAT3_(729)', 'STAT family protein binding_(122947)']\n" - ] - } - ], + "outputs": [], "source": [ - "# Find all nodes that start with 'ST'\n", - "st_nodes = [node for node in nodes_list if node.startswith('ST')]\n", + "res = []\n", + "for idx, row in species_descriptions.iterrows():\n", + " best_node = fetch_code_in_graph(row['best_node'], G)\n", + " res += [best_node]\n", "\n", - "if st_nodes:\n", - " print(f\"Nodes starting with 'ST': {st_nodes}\")\n", - "else:\n", - " print(\"No nodes start with 'ST'.\")\n" + "species_descriptions['best_code'] = res" ] + }, + { + "cell_type": "code", + "execution_count": 22, + "id": "96db0b07-74df-4ff6-b851-a6f273d828ae", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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idnamebackgroundBERT_embeddingbest_nodebest_code
0mwf626e95e_543f_41e4_aad4_c6bf60ab345bIL6Based on the provided context, IL6 (interleuki...[[-0.38310152, 0.14221658, 0.30036777, -0.1971...CLEC7A (Dectin-1) signaling_(62768)R-HSA-5607764
1mwbbbce920_e8dd_4320_9386_fc94bfb2fc99sgp130Based on the provided context, the species 'sg...[[-0.39776802, 0.102813065, 0.276282, -0.17234...Interleukin-2 signaling_(128499)R-HSA-9020558
2mw810ff751_fa4e_4143_bd50_169b3e325e1esR_IL6_sgp130Based on the provided context, 'sR_IL6_sgp130'...[[-0.41926485, 0.05604683, 0.31495243, -0.0975...Interleukin-6 signaling_(128814)R-HSA-1059683
3mw114aa90f_5f5b_4fe8_9406_361c8489b6a1CRPBased on the provided context, CRP, or C-react...[[-0.44731545, 0.21171626, 0.22573717, -0.1713...Immunoregulatory interactions between a Lympho...R-HSA-198933
4mw30ae63db_6cd3_4b6f_93ad_3350cd360bccsRFrom the provided documents, there is no speci...[[-0.24422143, 0.22741008, 0.3196285, -0.20558...G alpha (12/13) signalling events_(128349)R-HSA-416482
5mw03db56ac_8dc6_4931_ae82_fef706d2ee3dsR_IL6Based on the provided context and general know...[[-0.38647282, 0.14947572, 0.37386724, -0.2257...Interleukin-6 signaling_(128814)R-HSA-1059683
6mwf345ed7a_0622_403c_b816_c8749a2c9dedAbThe context provided from the documents appear...[[-0.35710102, 0.27481169, 0.15268518, -0.2598...Interleukin-2 signaling_(128499)R-HSA-9020558
7mw1da111f2_a036_4392_8512_015005bdcbb7Ab_sRThe context provided does not contain specific...[[-0.2979536, 0.22971633, 0.2543159, -0.238324...Cytoprotection by HMOX1_(63064)R-HSA-9707564
8mw9947742a_0e4b_4636_9a4b_b6eef2a8f6acAb_sR_IL6From the context provided, there is no direct ...[[-0.3250525, 0.17176488, 0.2808889, -0.207119...Interleukin-2 signaling_(128499)R-HSA-9020558
9CRP_Suppression___CRP Suppression (%)Based on the context provided, \"CRP Suppressio...[[-0.47315472, 0.18459623, 0.24418907, -0.1895...Immunoregulatory interactions between a Lympho...R-HSA-198933
10CRP____of_baselineCRP (% of baseline)Based on the provided context and general know...[[-0.36008894, 0.18380362, 0.27387857, -0.2149...Tezacaftor_(15045)DB11712
11mw80848184_e2dd_47ce_86d7_7a21479342bdgp130Gp130 is an important protein involved in the ...[[-0.35777402, 0.12645116, 0.3562525, -0.23347...Interleukin-6 signaling_(128814)R-HSA-1059683
12mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55aR_IL6_gp130The species named 'R_IL6_gp130', provided with...[[-0.3070841, 0.14377351, 0.28311783, -0.18864...CLEC7A (Dectin-1) signaling_(62768)R-HSA-5607764
13mw4638f126_8cb8_4021_ab41_6ae195743ba0sR_IL6The species referred to as 'sR_IL6' in the pro...[[-0.41398245, 0.14713271, 0.3669848, -0.26080...Interleukin-6 signaling_(128814)R-HSA-1059683
14mw10315fa3_6f13_4618_bda8_a8694bd3c374RBased on the provided context, the document di...[[-0.35146654, 0.103895366, 0.30642122, -0.249...Interleukin-2 signaling_(128499)R-HSA-9020558
15mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1IL6IL-6 (Interleukin-6) is a cytokine, a type of ...[[-0.4627117, 0.097201906, 0.3234311, -0.21945...Interleukin-6 signaling_(128814)R-HSA-1059683
16mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83R_IL6The context provided from the document does no...[[-0.3934079, 0.2065271, 0.28749886, -0.225543...CLEC7A (Dectin-1) signaling_(62768)R-HSA-5607764
17mw0eb6c959_d408_45a0_a450_928b8c5876bbRactiveThe provided context does not specifically men...[[-0.24638735, 0.19071835, 0.17823611, -0.2357...The NLRP3 inflammasome_(128804)R-HSA-844456
18mw42054cd7_17af_46da_970c_7f99151906adSTAT3STAT3, or Signal Transducer and Activator of T...[[-0.3920762, 0.21867904, 0.31682876, -0.18099...MyD88:MAL(TIRAP) cascade initiated on plasma m...R-HSA-166058
19mw39c2e431_fdc3_4964_be29_6ca856620b1bpSTAT3Based on the context provided, pSTAT3 is the p...[[-0.31854075, 0.21612896, 0.36678687, -0.2491...NOD1/2 Signaling Pathway_(127908)R-HSA-168638
20mwd5313618_89eb_4c8c_bc82_66f10f966349CRPC-reactive protein (CRP) is a well-known marke...[[-0.4524013, 0.21426782, 0.26746103, -0.18231...Regulation of Complement cascade_(127866)R-HSA-977606
21mw2e464cf3_a09c_4b7c_9f3c_06720016a48esRThe provided context primarily discusses the i...[[-0.25064346, 0.32432884, 0.2525344, -0.19168...Immunoregulatory interactions between a Lympho...R-HSA-198933
22mw36ea78c1_ed71_4def_96d3_857a442d7195CRPExtracellularThe context provided does not specifically men...[[-0.35434383, 0.24616718, 0.26500684, -0.1196...Immunoregulatory interactions between a Lympho...R-HSA-198933
23mw147d30ec_478e_4090_b496_128a131d29ebsgp130Based on the provided context, sgp130 appears ...[[-0.37740308, 0.07933396, 0.32603347, -0.1108...Interleukin-6 signaling_(128814)R-HSA-1059683
24mwab41493c_6349_45f1_a226_3030cfed0e06sR_IL6_sgp130Based on the context provided and general know...[[-0.37221003, 0.1744852, 0.30792367, -0.15933...Interleukin-2 signaling_(128499)R-HSA-9020558
25mwf405687b_7401_44ec_a0d6_4a2b35c13e8aAb_sRBased on the provided context, there is no dir...[[-0.23842902, 0.18786879, 0.2620399, -0.21784...CLEC7A (Dectin-1) signaling_(62768)R-HSA-5607764
26mw3667a5e1_02c9_44a0_acb4_b0431faa822dAbThe species denoted as 'Ab' in the context app...[[-0.52765065, 0.27688166, 0.20610718, -0.2776...Cytoprotection by HMOX1_(63064)R-HSA-9707564
27mw772cbf20_3fc1_4800_ae59_77884f1ae333Ab_RBased on the provided context from the documen...[[-0.1863702, 0.36686182, 0.22280839, -0.21697...Immunoregulatory interactions between a Lympho...R-HSA-198933
28mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cfAb_sR_IL6Based on the context provided, there is no exp...[[-0.3548704, 0.1917099, 0.28657728, -0.262703...Interleukin-2 signaling_(128499)R-HSA-9020558
29mw7becb5fe_8da8_4285_a821_0d77ad811b62sR_IL6Based on the context provided, specific inform...[[-0.28405702, 0.10858213, 0.32111079, -0.2300...Interleukin-2 signaling_(128499)R-HSA-9020558
30mw8c9107e6_f51d_442d_b2dc_2bfdbb8482cagp130Gp130, also known as glycoprotein 130, is a cr...[[-0.47336444, 0.08036472, 0.37820706, -0.2123...Interleukin-6 signaling_(128814)R-HSA-1059683
31mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9R_IL6_gp130Based on the context provided, it appears ther...[[-0.3776276, 0.21458092, 0.3001521, -0.152129...Interleukin-6 signaling_(128814)R-HSA-1059683
32mw6cce2109_0e32_4dd9_98ec_41173e8ef07dRactiveThe provided context does not contain direct i...[[-0.2948512, 0.27886307, 0.23734306, -0.22463...Regulation of TLR by endogenous ligand_(127918)R-HSA-5686938
33mw2b255f94_8018_4b99_bde8_918eeac45446STAT3STAT3, or Signal Transducer and Activator of T...[[-0.32530716, 0.24720953, 0.26123106, -0.2493...Growth hormone receptor signaling_(127694)R-HSA-982772
34mw48867e93_f170_44e8_ac7a_185b23e1bf3bpSTAT3pSTAT3, or phosphorylated Signal Transducer an...[[-0.37683305, 0.3004347, 0.30100918, -0.21106...Signaling by MST1_(129128)R-HSA-8852405
35mw0083d743_836f_4238_a17f_4602193d5bc0geneProductThe context provided does not specifically men...[[-0.30782086, 0.2336929, 0.23015884, -0.16083...Immunoregulatory interactions between a Lympho...R-HSA-198933
36mwd31f52cc_04e7_40e0_885f_c7b2d9e62215sRBased on the provided context, the species nam...[[-0.3048136, 0.16629891, 0.3336691, -0.178628...Interleukin-2 signaling_(128499)R-HSA-9020558
37mw2c9b0499_3325_4394_8af3_bbf653a944a0IL6Based on the provided context, here is the bac...[[-0.4397936, 0.15727538, 0.35291147, -0.22082...Interleukin-6 signaling_(128814)R-HSA-1059683
38mwd65b5b39_dc1b_4e77_a999_67277a880e5esgp130sgp130, as described in the context, refers to...[[-0.4935615, 0.10821018, 0.1830138, -0.252587...Cytoprotection by HMOX1_(63064)R-HSA-9707564
39mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3sR_IL6_sgp130The species 'sR_IL6_sgp130' likely refers to a...[[-0.2861055, 0.08323312, 0.34479225, -0.18034...Interleukin-6 signaling_(128814)R-HSA-1059683
40mwf7796221_1fea_4274_a93e_c00adbf5778cAbBased on the provided context, there is no dir...[[-0.37095174, 0.32116163, 0.20662963, -0.2790...Interleukin-2 signaling_(128499)R-HSA-9020558
41mw5d764bb8_5693_4ac8_9557_f65992cc5eb0Ab_sRThe provided context does not include specific...[[-0.15027289, 0.31890064, 0.17519885, -0.2029...Immunoregulatory interactions between a Lympho...R-HSA-198933
42mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2Ab_sR_IL6The species \"Ab_sR_IL6\" appears to be involved...[[-0.3795819, 0.24610856, 0.26605865, -0.28016...Interleukin-2 signaling_(128499)R-HSA-9020558
43mwbc2f5464_81e5_43fd_8b39_f5a2756af72fAbThe provided documents include information tha...[[-0.46518034, 0.22024783, 0.28029412, -0.2428...Interleukin-2 signaling_(128499)R-HSA-9020558
\n", + "
" + ], + "text/plain": [ + " id name \\\n", + "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 \n", + "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130 \n", + "2 mw810ff751_fa4e_4143_bd50_169b3e325e1e sR_IL6_sgp130 \n", + "3 mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 CRP \n", + "4 mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc sR \n", + "5 mw03db56ac_8dc6_4931_ae82_fef706d2ee3d sR_IL6 \n", + "6 mwf345ed7a_0622_403c_b816_c8749a2c9ded Ab \n", + "7 mw1da111f2_a036_4392_8512_015005bdcbb7 Ab_sR \n", + "8 mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac Ab_sR_IL6 \n", + "9 CRP_Suppression___ CRP Suppression (%) \n", + "10 CRP____of_baseline CRP (% of baseline) \n", + "11 mw80848184_e2dd_47ce_86d7_7a21479342bd gp130 \n", + "12 mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a R_IL6_gp130 \n", + "13 mw4638f126_8cb8_4021_ab41_6ae195743ba0 sR_IL6 \n", + "14 mw10315fa3_6f13_4618_bda8_a8694bd3c374 R \n", + "15 mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 IL6 \n", + "16 mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 R_IL6 \n", + "17 mw0eb6c959_d408_45a0_a450_928b8c5876bb Ractive \n", + "18 mw42054cd7_17af_46da_970c_7f99151906ad STAT3 \n", + "19 mw39c2e431_fdc3_4964_be29_6ca856620b1b pSTAT3 \n", + "20 mwd5313618_89eb_4c8c_bc82_66f10f966349 CRP \n", + "21 mw2e464cf3_a09c_4b7c_9f3c_06720016a48e sR \n", + "22 mw36ea78c1_ed71_4def_96d3_857a442d7195 CRPExtracellular \n", + "23 mw147d30ec_478e_4090_b496_128a131d29eb sgp130 \n", + "24 mwab41493c_6349_45f1_a226_3030cfed0e06 sR_IL6_sgp130 \n", + "25 mwf405687b_7401_44ec_a0d6_4a2b35c13e8a Ab_sR \n", + "26 mw3667a5e1_02c9_44a0_acb4_b0431faa822d Ab \n", + "27 mw772cbf20_3fc1_4800_ae59_77884f1ae333 Ab_R \n", + "28 mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf Ab_sR_IL6 \n", + "29 mw7becb5fe_8da8_4285_a821_0d77ad811b62 sR_IL6 \n", + "30 mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca gp130 \n", + "31 mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9 R_IL6_gp130 \n", + "32 mw6cce2109_0e32_4dd9_98ec_41173e8ef07d Ractive \n", + "33 mw2b255f94_8018_4b99_bde8_918eeac45446 STAT3 \n", + "34 mw48867e93_f170_44e8_ac7a_185b23e1bf3b pSTAT3 \n", + "35 mw0083d743_836f_4238_a17f_4602193d5bc0 geneProduct \n", + "36 mwd31f52cc_04e7_40e0_885f_c7b2d9e62215 sR \n", + "37 mw2c9b0499_3325_4394_8af3_bbf653a944a0 IL6 \n", + "38 mwd65b5b39_dc1b_4e77_a999_67277a880e5e sgp130 \n", + "39 mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 sR_IL6_sgp130 \n", + "40 mwf7796221_1fea_4274_a93e_c00adbf5778c Ab \n", + "41 mw5d764bb8_5693_4ac8_9557_f65992cc5eb0 Ab_sR \n", + "42 mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2 Ab_sR_IL6 \n", + "43 mwbc2f5464_81e5_43fd_8b39_f5a2756af72f Ab \n", + "\n", + " background \\\n", + "0 Based on the provided context, IL6 (interleuki... \n", + "1 Based on the provided context, the species 'sg... \n", + "2 Based on the provided context, 'sR_IL6_sgp130'... \n", + "3 Based on the provided context, CRP, or C-react... \n", + "4 From the provided documents, there is no speci... \n", + "5 Based on the provided context and general know... \n", + "6 The context provided from the documents appear... \n", + "7 The context provided does not contain specific... \n", + "8 From the context provided, there is no direct ... \n", + "9 Based on the context provided, \"CRP Suppressio... \n", + "10 Based on the provided context and general know... \n", + "11 Gp130 is an important protein involved in the ... \n", + "12 The species named 'R_IL6_gp130', provided with... \n", + "13 The species referred to as 'sR_IL6' in the pro... \n", + "14 Based on the provided context, the document di... \n", + "15 IL-6 (Interleukin-6) is a cytokine, a type of ... \n", + "16 The context provided from the document does no... \n", + "17 The provided context does not specifically men... \n", + "18 STAT3, or Signal Transducer and Activator of T... \n", + "19 Based on the context provided, pSTAT3 is the p... \n", + "20 C-reactive protein (CRP) is a well-known marke... \n", + "21 The provided context primarily discusses the i... \n", + "22 The context provided does not specifically men... \n", + "23 Based on the provided context, sgp130 appears ... \n", + "24 Based on the context provided and general know... \n", + "25 Based on the provided context, there is no dir... \n", + "26 The species denoted as 'Ab' in the context app... \n", + "27 Based on the provided context from the documen... \n", + "28 Based on the context provided, there is no exp... \n", + "29 Based on the context provided, specific inform... \n", + "30 Gp130, also known as glycoprotein 130, is a cr... \n", + "31 Based on the context provided, it appears ther... \n", + "32 The provided context does not contain direct i... \n", + "33 STAT3, or Signal Transducer and Activator of T... \n", + "34 pSTAT3, or phosphorylated Signal Transducer an... \n", + "35 The context provided does not specifically men... \n", + "36 Based on the provided context, the species nam... \n", + "37 Based on the provided context, here is the bac... \n", + "38 sgp130, as described in the context, refers to... \n", + "39 The species 'sR_IL6_sgp130' likely refers to a... \n", + "40 Based on the provided context, there is no dir... \n", + "41 The provided context does not include specific... \n", + "42 The species \"Ab_sR_IL6\" appears to be involved... \n", + "43 The provided documents include information tha... \n", + "\n", + " BERT_embedding \\\n", + "0 [[-0.38310152, 0.14221658, 0.30036777, -0.1971... \n", + "1 [[-0.39776802, 0.102813065, 0.276282, -0.17234... \n", + "2 [[-0.41926485, 0.05604683, 0.31495243, -0.0975... \n", + "3 [[-0.44731545, 0.21171626, 0.22573717, -0.1713... \n", + "4 [[-0.24422143, 0.22741008, 0.3196285, -0.20558... \n", + "5 [[-0.38647282, 0.14947572, 0.37386724, -0.2257... \n", + "6 [[-0.35710102, 0.27481169, 0.15268518, -0.2598... \n", + "7 [[-0.2979536, 0.22971633, 0.2543159, -0.238324... \n", + "8 [[-0.3250525, 0.17176488, 0.2808889, -0.207119... \n", + "9 [[-0.47315472, 0.18459623, 0.24418907, -0.1895... \n", + "10 [[-0.36008894, 0.18380362, 0.27387857, -0.2149... \n", + "11 [[-0.35777402, 0.12645116, 0.3562525, -0.23347... \n", + "12 [[-0.3070841, 0.14377351, 0.28311783, -0.18864... \n", + "13 [[-0.41398245, 0.14713271, 0.3669848, -0.26080... \n", + "14 [[-0.35146654, 0.103895366, 0.30642122, -0.249... \n", + "15 [[-0.4627117, 0.097201906, 0.3234311, -0.21945... \n", + "16 [[-0.3934079, 0.2065271, 0.28749886, -0.225543... \n", + "17 [[-0.24638735, 0.19071835, 0.17823611, -0.2357... \n", + "18 [[-0.3920762, 0.21867904, 0.31682876, -0.18099... \n", + "19 [[-0.31854075, 0.21612896, 0.36678687, -0.2491... \n", + "20 [[-0.4524013, 0.21426782, 0.26746103, -0.18231... \n", + "21 [[-0.25064346, 0.32432884, 0.2525344, -0.19168... \n", + "22 [[-0.35434383, 0.24616718, 0.26500684, -0.1196... \n", + "23 [[-0.37740308, 0.07933396, 0.32603347, -0.1108... \n", + "24 [[-0.37221003, 0.1744852, 0.30792367, -0.15933... \n", + "25 [[-0.23842902, 0.18786879, 0.2620399, -0.21784... \n", + "26 [[-0.52765065, 0.27688166, 0.20610718, -0.2776... \n", + "27 [[-0.1863702, 0.36686182, 0.22280839, -0.21697... \n", + "28 [[-0.3548704, 0.1917099, 0.28657728, -0.262703... \n", + "29 [[-0.28405702, 0.10858213, 0.32111079, -0.2300... \n", + "30 [[-0.47336444, 0.08036472, 0.37820706, -0.2123... \n", + "31 [[-0.3776276, 0.21458092, 0.3001521, -0.152129... \n", + "32 [[-0.2948512, 0.27886307, 0.23734306, -0.22463... \n", + "33 [[-0.32530716, 0.24720953, 0.26123106, -0.2493... \n", + "34 [[-0.37683305, 0.3004347, 0.30100918, -0.21106... \n", + "35 [[-0.30782086, 0.2336929, 0.23015884, -0.16083... \n", + "36 [[-0.3048136, 0.16629891, 0.3336691, -0.178628... \n", + "37 [[-0.4397936, 0.15727538, 0.35291147, -0.22082... \n", + "38 [[-0.4935615, 0.10821018, 0.1830138, -0.252587... \n", + "39 [[-0.2861055, 0.08323312, 0.34479225, -0.18034... \n", + "40 [[-0.37095174, 0.32116163, 0.20662963, -0.2790... \n", + "41 [[-0.15027289, 0.31890064, 0.17519885, -0.2029... \n", + "42 [[-0.3795819, 0.24610856, 0.26605865, -0.28016... \n", + "43 [[-0.46518034, 0.22024783, 0.28029412, -0.2428... \n", + "\n", + " best_node best_code \n", + "0 CLEC7A (Dectin-1) signaling_(62768) R-HSA-5607764 \n", + "1 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "2 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "3 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", + "4 G alpha (12/13) signalling events_(128349) R-HSA-416482 \n", + "5 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "6 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "7 Cytoprotection by HMOX1_(63064) R-HSA-9707564 \n", + "8 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "9 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", + "10 Tezacaftor_(15045) DB11712 \n", + "11 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "12 CLEC7A (Dectin-1) signaling_(62768) R-HSA-5607764 \n", + "13 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "14 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "15 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "16 CLEC7A (Dectin-1) signaling_(62768) R-HSA-5607764 \n", + "17 The NLRP3 inflammasome_(128804) R-HSA-844456 \n", + "18 MyD88:MAL(TIRAP) cascade initiated on plasma m... R-HSA-166058 \n", + "19 NOD1/2 Signaling Pathway_(127908) R-HSA-168638 \n", + "20 Regulation of Complement cascade_(127866) R-HSA-977606 \n", + "21 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", + "22 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", + "23 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "24 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "25 CLEC7A (Dectin-1) signaling_(62768) R-HSA-5607764 \n", + "26 Cytoprotection by HMOX1_(63064) R-HSA-9707564 \n", + "27 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", + "28 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "29 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "30 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "31 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "32 Regulation of TLR by endogenous ligand_(127918) R-HSA-5686938 \n", + "33 Growth hormone receptor signaling_(127694) R-HSA-982772 \n", + "34 Signaling by MST1_(129128) R-HSA-8852405 \n", + "35 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", + "36 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "37 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "38 Cytoprotection by HMOX1_(63064) R-HSA-9707564 \n", + "39 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", + "40 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "41 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", + "42 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", + "43 Interleukin-2 signaling_(128499) R-HSA-9020558 " + ] + }, + "execution_count": 22, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "species_descriptions" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "id": "70697134-924f-4594-9dd1-c6e52bc166c0", + "metadata": {}, + "outputs": [], + "source": [] + }, + { + "cell_type": "code", + "execution_count": null, + "id": "e1ae5b43-e036-48a9-8c4b-924e5fcbc87d", + "metadata": {}, + "outputs": [], + "source": [] } ], "metadata": { From 1150cd4ad25236983f1ed9fd418750f5c5342084 Mon Sep 17 00:00:00 2001 From: Inigo Date: Fri, 7 Mar 2025 14:55:30 +0000 Subject: [PATCH 13/14] Last changes --- notebook/embeddings_and_evaluation.ipynb | 8859 ++-------------------- notebook/model537_mapping.csv | 45 + notebook/sbml_rag_notebook.ipynb | 4 +- notebook/species_backgrounds.csv | 653 -- notebook/species_backgrounds_final.csv | 751 ++ 5 files changed, 1638 insertions(+), 8674 deletions(-) create mode 100644 notebook/model537_mapping.csv delete mode 100644 notebook/species_backgrounds.csv create mode 100644 notebook/species_backgrounds_final.csv diff --git a/notebook/embeddings_and_evaluation.ipynb b/notebook/embeddings_and_evaluation.ipynb index ba041bb8..2b3926cd 100644 --- a/notebook/embeddings_and_evaluation.ipynb +++ b/notebook/embeddings_and_evaluation.ipynb @@ -7,7 +7,6 @@ "source": [ "# Model embeddings and similarity assignment\n", "\n", - "This notebook \n", "\n", "**What this notebook does:**\n", "1. Loads a .csv containing species name and their backgrounds\n", @@ -17,6 +16,19 @@ "5. We keep the best node in the graph and extract the code within the KG." ] }, + { + "attachments": { + "6b290b88-6181-44b5-9bac-19aeb8191064.png": { + "image/png": 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" + } + }, + "cell_type": "markdown", + "id": "20291366-203e-4f38-8083-d22d5d5f1ff4", + "metadata": {}, + "source": [ + "![image.png](attachment:6b290b88-6181-44b5-9bac-19aeb8191064.png)" + ] + }, { "cell_type": "code", "execution_count": 1, @@ -52,7 +64,7 @@ }, { "cell_type": "code", - "execution_count": 17, + "execution_count": 2, "id": "987958fe-b489-44b9-a861-4a5b17530380", "metadata": {}, "outputs": [], @@ -63,7 +75,7 @@ }, { "cell_type": "code", - "execution_count": 2, + "execution_count": 3, "id": "f724e7f5-1dbf-45cb-a60d-f48180b7adab", "metadata": {}, "outputs": [], @@ -73,7 +85,7 @@ }, { "cell_type": "code", - "execution_count": 3, + "execution_count": 4, "id": "a6619d22-6e3e-4167-9231-acfd5a69eeaa", "metadata": {}, "outputs": [ @@ -83,7 +95,7 @@ "Data(x=[3426, 768], edge_index=[2, 12752], edge_attr=[12752, 768], node_id=[3426], node_name=[3426], node_type=[3426], enriched_node=[3426], key=[12752], head_id=[12752], head_name=[12752], tail_id=[12752], tail_name=[12752], edge_type=[12752], enriched_edge=[12752])" ] }, - "execution_count": 3, + "execution_count": 4, "metadata": {}, "output_type": "execute_result" } @@ -97,7 +109,7 @@ }, { "cell_type": "code", - "execution_count": 4, + "execution_count": 5, "id": "d62c7c8d-760f-44d3-9c37-ddafbd45fd3e", "metadata": {}, "outputs": [], @@ -129,13 +141,13 @@ }, { "cell_type": "code", - "execution_count": 5, + "execution_count": 6, "id": "53dea1e5-24b8-4705-ac23-0ef1d6f7883e", "metadata": {}, "outputs": [ { "data": { - "image/png": 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", + "image/png": 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", "text/plain": [ "
" ] @@ -173,7 +185,7 @@ }, { "cell_type": "code", - "execution_count": 6, + "execution_count": 7, "id": "0273b3be-d420-4a2b-b1ca-de0a3e05e8e6", "metadata": {}, "outputs": [], @@ -185,7 +197,7 @@ }, { "cell_type": "code", - "execution_count": 7, + "execution_count": 8, "id": "d9c7affa-2558-433d-a3b1-b5dcf31b7ccd", "metadata": {}, "outputs": [], @@ -220,7 +232,7 @@ "metadata": {}, "outputs": [], "source": [ - "species_descriptions = pd.read_csv('species_backgrounds.csv')\n", + "species_descriptions = pd.read_csv('species_backgrounds_final.csv')\n", "res = []\n", "for idx, row in species_descriptions.iterrows():\n", " res += [get_text_embedding(row['background'])]\n", @@ -256,6 +268,8 @@ " \n", " id\n", " name\n", + " original_name\n", + " compartment\n", " background\n", " BERT_embedding\n", " \n", @@ -264,453 +278,587 @@ " \n", " 0\n", " mwf626e95e_543f_41e4_aad4_c6bf60ab345b\n", + " IL6{serum}\n", " IL6\n", - " Based on the provided context, IL6 (interleuki...\n", - " [[-0.38310152, 0.14221658, 0.30036777, -0.1971...\n", + " serum\n", + " Interleukin 6 (IL-6) is a cytokine with signif...\n", + " [[-0.36046556, 0.1984801, 0.34831223, -0.13759...\n", " \n", " \n", " 1\n", " mwbbbce920_e8dd_4320_9386_fc94bfb2fc99\n", + " sgp130{serum}\n", " sgp130\n", - " Based on the provided context, the species 'sg...\n", - " [[-0.39776802, 0.102813065, 0.276282, -0.17234...\n", + " serum\n", + " The provided documents do not offer explicit i...\n", + " [[-0.33606362, 0.14078653, 0.28409472, -0.1816...\n", " \n", " \n", " 2\n", " mw810ff751_fa4e_4143_bd50_169b3e325e1e\n", + " sR_IL6_sgp130{serum}\n", " sR_IL6_sgp130\n", - " Based on the provided context, 'sR_IL6_sgp130'...\n", - " [[-0.41926485, 0.05604683, 0.31495243, -0.0975...\n", + " serum\n", + " Based on the provided context and general know...\n", + " [[-0.35146952, 0.10439779, 0.35805824, -0.1242...\n", " \n", " \n", " 3\n", " mw114aa90f_5f5b_4fe8_9406_361c8489b6a1\n", + " CRP{serum}\n", " CRP\n", - " Based on the provided context, CRP, or C-react...\n", - " [[-0.44731545, 0.21171626, 0.22573717, -0.1713...\n", + " serum\n", + " C-reactive protein (CRP) is an acute-phase pro...\n", + " [[-0.51451033, 0.34030703, 0.27825356, -0.1979...\n", " \n", " \n", " 4\n", " mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc\n", + " sR{serum}\n", " sR\n", - " From the provided documents, there is no speci...\n", - " [[-0.24422143, 0.22741008, 0.3196285, -0.20558...\n", + " serum\n", + " The context provided from the document does no...\n", + " [[-0.19817938, 0.3326699, 0.28404108, -0.11455...\n", " \n", " \n", " 5\n", " mw03db56ac_8dc6_4931_ae82_fef706d2ee3d\n", + " sR_IL6{serum}\n", " sR_IL6\n", - " Based on the provided context and general know...\n", - " [[-0.38647282, 0.14947572, 0.37386724, -0.2257...\n", + " serum\n", + " Based on the provided context, there is no spe...\n", + " [[-0.38143575, 0.16730621, 0.33593783, -0.1761...\n", " \n", " \n", " 6\n", " mwf345ed7a_0622_403c_b816_c8749a2c9ded\n", + " Ab{serum}\n", " Ab\n", - " The context provided from the documents appear...\n", - " [[-0.35710102, 0.27481169, 0.15268518, -0.2598...\n", + " serum\n", + " Based on the provided context and familiar pri...\n", + " [[-0.26659864, 0.37297052, 0.12752607, -0.0740...\n", " \n", " \n", " 7\n", " mw1da111f2_a036_4392_8512_015005bdcbb7\n", + " Ab_sR{serum}\n", " Ab_sR\n", - " The context provided does not contain specific...\n", - " [[-0.2979536, 0.22971633, 0.2543159, -0.238324...\n", + " serum\n", + " The document context provided does not explici...\n", + " [[-0.25748405, 0.3326551, 0.22365786, -0.12952...\n", " \n", " \n", " 8\n", " mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac\n", + " Ab_sR_IL6{serum}\n", " Ab_sR_IL6\n", - " From the context provided, there is no direct ...\n", - " [[-0.3250525, 0.17176488, 0.2808889, -0.207119...\n", + " serum\n", + " The specific species 'Ab_sR_IL6{serum}' does n...\n", + " [[-0.37747848, 0.26106745, 0.29221672, -0.1456...\n", " \n", " \n", " 9\n", " CRP_Suppression___\n", + " CRP Suppression (%){serum}\n", " CRP Suppression (%)\n", - " Based on the context provided, \"CRP Suppressio...\n", - " [[-0.47315472, 0.18459623, 0.24418907, -0.1895...\n", + " serum\n", + " Based on the provided context, there is limite...\n", + " [[-0.4193665, 0.19158283, 0.2804547, -0.165872...\n", " \n", " \n", " 10\n", " CRP____of_baseline\n", + " CRP (% of baseline){serum}\n", " CRP (% of baseline)\n", - " Based on the provided context and general know...\n", - " [[-0.36008894, 0.18380362, 0.27387857, -0.2149...\n", + " serum\n", + " C-reactive protein (CRP) is an important bioma...\n", + " [[-0.39912638, 0.23087408, 0.27915168, -0.1415...\n", " \n", " \n", " 11\n", " mw80848184_e2dd_47ce_86d7_7a21479342bd\n", + " gp130{liver}\n", " gp130\n", - " Gp130 is an important protein involved in the ...\n", - " [[-0.35777402, 0.12645116, 0.3562525, -0.23347...\n", + " liver\n", + " Based on the provided context and general know...\n", + " [[-0.33445, 0.23918422, 0.2927546, -0.17028718...\n", " \n", " \n", " 12\n", " mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a\n", + " R_IL6_gp130{liver}\n", " R_IL6_gp130\n", - " The species named 'R_IL6_gp130', provided with...\n", - " [[-0.3070841, 0.14377351, 0.28311783, -0.18864...\n", + " liver\n", + " The species referred to as 'R_IL6_gp130{liver}...\n", + " [[-0.40478626, 0.17814767, 0.27589074, -0.1340...\n", " \n", " \n", " 13\n", " mw4638f126_8cb8_4021_ab41_6ae195743ba0\n", + " sR_IL6{liver}\n", " sR_IL6\n", - " The species referred to as 'sR_IL6' in the pro...\n", - " [[-0.41398245, 0.14713271, 0.3669848, -0.26080...\n", + " liver\n", + " The species referred to as 'sR_IL6{liver}' in ...\n", + " [[-0.45756304, 0.17891681, 0.36423725, -0.2334...\n", " \n", " \n", " 14\n", " mw10315fa3_6f13_4618_bda8_a8694bd3c374\n", + " R{liver}\n", " R\n", - " Based on the provided context, the document di...\n", - " [[-0.35146654, 0.103895366, 0.30642122, -0.249...\n", + " liver\n", + " The context provided does not include specific...\n", + " [[-0.4199063, 0.25244138, 0.23973583, -0.12047...\n", " \n", " \n", " 15\n", " mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1\n", + " IL6{liver}\n", " IL6\n", - " IL-6 (Interleukin-6) is a cytokine, a type of ...\n", - " [[-0.4627117, 0.097201906, 0.3234311, -0.21945...\n", + " liver\n", + " The provided context discusses the role of IL-...\n", + " [[-0.5299805, 0.20470381, 0.21622677, -0.16921...\n", " \n", " \n", " 16\n", " mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83\n", + " R_IL6{liver}\n", " R_IL6\n", - " The context provided from the document does no...\n", - " [[-0.3934079, 0.2065271, 0.28749886, -0.225543...\n", + " liver\n", + " The provided documents mention several compone...\n", + " [[-0.40827248, 0.1906287, 0.36825097, -0.23810...\n", " \n", " \n", " 17\n", " mw0eb6c959_d408_45a0_a450_928b8c5876bb\n", + " Ractive{liver}\n", " Ractive\n", - " The provided context does not specifically men...\n", - " [[-0.24638735, 0.19071835, 0.17823611, -0.2357...\n", + " liver\n", + " The context provided does not contain specific...\n", + " [[-0.29601544, 0.32257238, 0.11635402, -0.1388...\n", " \n", " \n", " 18\n", " mw42054cd7_17af_46da_970c_7f99151906ad\n", + " STAT3{liver}\n", " STAT3\n", - " STAT3, or Signal Transducer and Activator of T...\n", - " [[-0.3920762, 0.21867904, 0.31682876, -0.18099...\n", + " liver\n", + " Based on the provided context, the specific in...\n", + " [[-0.48407704, 0.26490304, 0.2329331, -0.23542...\n", " \n", " \n", " 19\n", " mw39c2e431_fdc3_4964_be29_6ca856620b1b\n", + " pSTAT3{liver}\n", " pSTAT3\n", - " Based on the context provided, pSTAT3 is the p...\n", - " [[-0.31854075, 0.21612896, 0.36678687, -0.2491...\n", + " liver\n", + " The context provided does not contain specific...\n", + " [[-0.31865203, 0.20982854, 0.33414608, -0.1467...\n", " \n", " \n", " 20\n", " mwd5313618_89eb_4c8c_bc82_66f10f966349\n", + " CRP{liver}\n", " CRP\n", - " C-reactive protein (CRP) is a well-known marke...\n", - " [[-0.4524013, 0.21426782, 0.26746103, -0.18231...\n", + " liver\n", + " Based on the given context, there is no specif...\n", + " [[-0.28650454, 0.28451994, 0.22697207, -0.1883...\n", " \n", " \n", " 21\n", " mw2e464cf3_a09c_4b7c_9f3c_06720016a48e\n", + " sR{liver}\n", " sR\n", - " The provided context primarily discusses the i...\n", - " [[-0.25064346, 0.32432884, 0.2525344, -0.19168...\n", + " liver\n", + " The provided context does not contain specific...\n", + " [[-0.3657858, 0.18391879, 0.26731104, -0.14256...\n", " \n", " \n", " 22\n", " mw36ea78c1_ed71_4def_96d3_857a442d7195\n", + " CRPExtracellular{liver}\n", " CRPExtracellular\n", - " The context provided does not specifically men...\n", - " [[-0.35434383, 0.24616718, 0.26500684, -0.1196...\n", + " liver\n", + " C-reactive protein (CRP) is an acute-phase pro...\n", + " [[-0.52379715, 0.26640716, 0.24741346, -0.2049...\n", " \n", " \n", " 23\n", " mw147d30ec_478e_4090_b496_128a131d29eb\n", + " sgp130{liver}\n", " sgp130\n", - " Based on the provided context, sgp130 appears ...\n", - " [[-0.37740308, 0.07933396, 0.32603347, -0.1108...\n", + " liver\n", + " The provided context does not specifically men...\n", + " [[-0.41315806, 0.19693111, 0.18671003, -0.1230...\n", " \n", " \n", " 24\n", " mwab41493c_6349_45f1_a226_3030cfed0e06\n", + " sR_IL6_sgp130{liver}\n", " sR_IL6_sgp130\n", - " Based on the context provided and general know...\n", - " [[-0.37221003, 0.1744852, 0.30792367, -0.15933...\n", + " liver\n", + " The species 'sR_IL6_sgp130{liver}' likely repr...\n", + " [[-0.43109208, 0.25532103, 0.27182448, -0.1714...\n", " \n", " \n", " 25\n", " mwf405687b_7401_44ec_a0d6_4a2b35c13e8a\n", + " Ab_sR{liver}\n", " Ab_sR\n", - " Based on the provided context, there is no dir...\n", - " [[-0.23842902, 0.18786879, 0.2620399, -0.21784...\n", + " liver\n", + " The provided context does not specifically men...\n", + " [[-0.31681302, 0.38205892, 0.13448949, -0.1530...\n", " \n", " \n", " 26\n", " mw3667a5e1_02c9_44a0_acb4_b0431faa822d\n", + " Ab{liver}\n", " Ab\n", - " The species denoted as 'Ab' in the context app...\n", - " [[-0.52765065, 0.27688166, 0.20610718, -0.2776...\n", + " liver\n", + " Based on the provided context, there appears t...\n", + " [[-0.25571656, 0.41298026, 0.169575, -0.146192...\n", " \n", " \n", " 27\n", " mw772cbf20_3fc1_4800_ae59_77884f1ae333\n", + " Ab_R{liver}\n", " Ab_R\n", - " Based on the provided context from the documen...\n", - " [[-0.1863702, 0.36686182, 0.22280839, -0.21697...\n", + " liver\n", + " The context provided does not offer specific i...\n", + " [[-0.2570913, 0.29179507, 0.19184656, -0.14854...\n", " \n", " \n", " 28\n", " mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf\n", + " Ab_sR_IL6{liver}\n", " Ab_sR_IL6\n", - " Based on the context provided, there is no exp...\n", - " [[-0.3548704, 0.1917099, 0.28657728, -0.262703...\n", + " liver\n", + " Based on the provided context and general scie...\n", + " [[-0.3885418, 0.18170443, 0.34147617, -0.20549...\n", " \n", " \n", " 29\n", " mw7becb5fe_8da8_4285_a821_0d77ad811b62\n", + " sR_IL6{gut}\n", " sR_IL6\n", - " Based on the context provided, specific inform...\n", - " [[-0.28405702, 0.10858213, 0.32111079, -0.2300...\n", + " gut\n", + " The species referred to as 'sR_IL6{gut}' likel...\n", + " [[-0.4339128, 0.22657649, 0.25634766, -0.19923...\n", " \n", " \n", " 30\n", " mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca\n", + " gp130{gut}\n", " gp130\n", - " Gp130, also known as glycoprotein 130, is a cr...\n", - " [[-0.47336444, 0.08036472, 0.37820706, -0.2123...\n", + " gut\n", + " The context provided does not explicitly menti...\n", + " [[-0.39961886, 0.21250604, 0.20553315, -0.1531...\n", " \n", " \n", " 31\n", " mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9\n", + " R_IL6_gp130{gut}\n", " R_IL6_gp130\n", - " Based on the context provided, it appears ther...\n", - " [[-0.3776276, 0.21458092, 0.3001521, -0.152129...\n", + " gut\n", + " The context provided does not directly mention...\n", + " [[-0.4055007, 0.20729655, 0.2815721, -0.172021...\n", " \n", " \n", " 32\n", " mw6cce2109_0e32_4dd9_98ec_41173e8ef07d\n", + " Ractive{gut}\n", " Ractive\n", - " The provided context does not contain direct i...\n", - " [[-0.2948512, 0.27886307, 0.23734306, -0.22463...\n", + " gut\n", + " Based on the provided context, there is no spe...\n", + " [[-0.19464502, 0.30159003, 0.034058932, -0.134...\n", " \n", " \n", " 33\n", " mw2b255f94_8018_4b99_bde8_918eeac45446\n", + " STAT3{gut}\n", " STAT3\n", - " STAT3, or Signal Transducer and Activator of T...\n", - " [[-0.32530716, 0.24720953, 0.26123106, -0.2493...\n", + " gut\n", + " The context provided does not include specific...\n", + " [[-0.3604745, 0.23800118, 0.19214159, -0.21026...\n", " \n", " \n", " 34\n", " mw48867e93_f170_44e8_ac7a_185b23e1bf3b\n", + " pSTAT3{gut}\n", " pSTAT3\n", - " pSTAT3, or phosphorylated Signal Transducer an...\n", - " [[-0.37683305, 0.3004347, 0.30100918, -0.21106...\n", + " gut\n", + " The provided context does not contain direct i...\n", + " [[-0.41001073, 0.18395737, 0.21566965, -0.1557...\n", " \n", " \n", " 35\n", " mw0083d743_836f_4238_a17f_4602193d5bc0\n", + " geneProduct{gut}\n", " geneProduct\n", - " The context provided does not specifically men...\n", - " [[-0.30782086, 0.2336929, 0.23015884, -0.16083...\n", + " gut\n", + " Based on the context provided, there appears t...\n", + " [[-0.1892068, 0.32208663, 0.13539186, -0.07255...\n", " \n", " \n", " 36\n", " mwd31f52cc_04e7_40e0_885f_c7b2d9e62215\n", + " sR{gut}\n", " sR\n", - " Based on the provided context, the species nam...\n", - " [[-0.3048136, 0.16629891, 0.3336691, -0.178628...\n", + " gut\n", + " The context provided does not contain specific...\n", + " [[-0.366351, 0.21531877, 0.2917647, -0.1173586...\n", " \n", " \n", " 37\n", " mw2c9b0499_3325_4394_8af3_bbf653a944a0\n", + " IL6{gut}\n", " IL6\n", - " Based on the provided context, here is the bac...\n", - " [[-0.4397936, 0.15727538, 0.35291147, -0.22082...\n", + " gut\n", + " Based on the context provided, IL6{gut} likely...\n", + " [[-0.38345662, 0.14892936, 0.283594, -0.155339...\n", " \n", " \n", " 38\n", " mwd65b5b39_dc1b_4e77_a999_67277a880e5e\n", + " sgp130{gut}\n", " sgp130\n", - " sgp130, as described in the context, refers to...\n", - " [[-0.4935615, 0.10821018, 0.1830138, -0.252587...\n", + " gut\n", + " The species 'sgp130{gut}', likely derived from...\n", + " [[-0.44768405, 0.19976878, 0.17069031, -0.1916...\n", " \n", " \n", " 39\n", " mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3\n", + " sR_IL6_sgp130{gut}\n", " sR_IL6_sgp130\n", - " The species 'sR_IL6_sgp130' likely refers to a...\n", - " [[-0.2861055, 0.08323312, 0.34479225, -0.18034...\n", + " gut\n", + " Based on the provided context and general know...\n", + " [[-0.45934308, 0.19494462, 0.22395587, -0.1774...\n", " \n", " \n", " 40\n", " mwf7796221_1fea_4274_a93e_c00adbf5778c\n", + " Ab{gut}\n", " Ab\n", - " Based on the provided context, there is no dir...\n", - " [[-0.37095174, 0.32116163, 0.20662963, -0.2790...\n", + " gut\n", + " Based on the context provided and general know...\n", + " [[-0.3002606, 0.34374207, 0.15582994, -0.14586...\n", " \n", " \n", " 41\n", " mw5d764bb8_5693_4ac8_9557_f65992cc5eb0\n", + " Ab_sR{gut}\n", " Ab_sR\n", - " The provided context does not include specific...\n", - " [[-0.15027289, 0.31890064, 0.17519885, -0.2029...\n", + " gut\n", + " The context provided does not contain specific...\n", + " [[-0.3193748, 0.24593732, 0.22288847, -0.09116...\n", " \n", " \n", " 42\n", " mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2\n", + " Ab_sR_IL6{gut}\n", " Ab_sR_IL6\n", - " The species \"Ab_sR_IL6\" appears to be involved...\n", - " [[-0.3795819, 0.24610856, 0.26605865, -0.28016...\n", + " gut\n", + " The context does not provide explicit informat...\n", + " [[-0.44073004, 0.20752984, 0.22041091, -0.1554...\n", " \n", " \n", " 43\n", " mwbc2f5464_81e5_43fd_8b39_f5a2756af72f\n", + " Ab{peripheral}\n", " Ab\n", - " The provided documents include information tha...\n", - " [[-0.46518034, 0.22024783, 0.28029412, -0.2428...\n", + " peripheral\n", + " The context provided does not explicitly menti...\n", + " [[-0.15118778, 0.33757055, 0.18688324, -0.0879...\n", " \n", " \n", "\n", "" ], "text/plain": [ - " id name \\\n", - "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 \n", - "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130 \n", - "2 mw810ff751_fa4e_4143_bd50_169b3e325e1e sR_IL6_sgp130 \n", - "3 mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 CRP \n", - "4 mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc sR \n", - "5 mw03db56ac_8dc6_4931_ae82_fef706d2ee3d sR_IL6 \n", - "6 mwf345ed7a_0622_403c_b816_c8749a2c9ded Ab \n", - "7 mw1da111f2_a036_4392_8512_015005bdcbb7 Ab_sR \n", - "8 mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac Ab_sR_IL6 \n", - "9 CRP_Suppression___ CRP Suppression (%) \n", - "10 CRP____of_baseline CRP (% of baseline) \n", - "11 mw80848184_e2dd_47ce_86d7_7a21479342bd gp130 \n", - "12 mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a R_IL6_gp130 \n", - "13 mw4638f126_8cb8_4021_ab41_6ae195743ba0 sR_IL6 \n", - "14 mw10315fa3_6f13_4618_bda8_a8694bd3c374 R \n", - "15 mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 IL6 \n", - "16 mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 R_IL6 \n", - "17 mw0eb6c959_d408_45a0_a450_928b8c5876bb Ractive \n", - "18 mw42054cd7_17af_46da_970c_7f99151906ad STAT3 \n", - "19 mw39c2e431_fdc3_4964_be29_6ca856620b1b pSTAT3 \n", - "20 mwd5313618_89eb_4c8c_bc82_66f10f966349 CRP \n", - "21 mw2e464cf3_a09c_4b7c_9f3c_06720016a48e sR \n", - "22 mw36ea78c1_ed71_4def_96d3_857a442d7195 CRPExtracellular \n", - "23 mw147d30ec_478e_4090_b496_128a131d29eb sgp130 \n", - "24 mwab41493c_6349_45f1_a226_3030cfed0e06 sR_IL6_sgp130 \n", - "25 mwf405687b_7401_44ec_a0d6_4a2b35c13e8a Ab_sR \n", - "26 mw3667a5e1_02c9_44a0_acb4_b0431faa822d Ab \n", - "27 mw772cbf20_3fc1_4800_ae59_77884f1ae333 Ab_R \n", - "28 mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf Ab_sR_IL6 \n", - "29 mw7becb5fe_8da8_4285_a821_0d77ad811b62 sR_IL6 \n", - "30 mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca gp130 \n", - "31 mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9 R_IL6_gp130 \n", - "32 mw6cce2109_0e32_4dd9_98ec_41173e8ef07d Ractive \n", - "33 mw2b255f94_8018_4b99_bde8_918eeac45446 STAT3 \n", - "34 mw48867e93_f170_44e8_ac7a_185b23e1bf3b pSTAT3 \n", - "35 mw0083d743_836f_4238_a17f_4602193d5bc0 geneProduct \n", - "36 mwd31f52cc_04e7_40e0_885f_c7b2d9e62215 sR \n", - "37 mw2c9b0499_3325_4394_8af3_bbf653a944a0 IL6 \n", - "38 mwd65b5b39_dc1b_4e77_a999_67277a880e5e sgp130 \n", - "39 mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 sR_IL6_sgp130 \n", - "40 mwf7796221_1fea_4274_a93e_c00adbf5778c Ab \n", - "41 mw5d764bb8_5693_4ac8_9557_f65992cc5eb0 Ab_sR \n", - "42 mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2 Ab_sR_IL6 \n", - "43 mwbc2f5464_81e5_43fd_8b39_f5a2756af72f Ab \n", + " id name \\\n", + "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6{serum} \n", + "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130{serum} \n", + "2 mw810ff751_fa4e_4143_bd50_169b3e325e1e sR_IL6_sgp130{serum} \n", + "3 mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 CRP{serum} \n", + "4 mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc sR{serum} \n", + "5 mw03db56ac_8dc6_4931_ae82_fef706d2ee3d sR_IL6{serum} \n", + "6 mwf345ed7a_0622_403c_b816_c8749a2c9ded Ab{serum} \n", + "7 mw1da111f2_a036_4392_8512_015005bdcbb7 Ab_sR{serum} \n", + "8 mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac Ab_sR_IL6{serum} \n", + "9 CRP_Suppression___ CRP Suppression (%){serum} \n", + "10 CRP____of_baseline CRP (% of baseline){serum} \n", + "11 mw80848184_e2dd_47ce_86d7_7a21479342bd gp130{liver} \n", + "12 mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a R_IL6_gp130{liver} \n", + "13 mw4638f126_8cb8_4021_ab41_6ae195743ba0 sR_IL6{liver} \n", + "14 mw10315fa3_6f13_4618_bda8_a8694bd3c374 R{liver} \n", + "15 mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 IL6{liver} \n", + "16 mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 R_IL6{liver} \n", + "17 mw0eb6c959_d408_45a0_a450_928b8c5876bb Ractive{liver} \n", + "18 mw42054cd7_17af_46da_970c_7f99151906ad STAT3{liver} \n", + "19 mw39c2e431_fdc3_4964_be29_6ca856620b1b pSTAT3{liver} \n", + "20 mwd5313618_89eb_4c8c_bc82_66f10f966349 CRP{liver} \n", + "21 mw2e464cf3_a09c_4b7c_9f3c_06720016a48e sR{liver} \n", + "22 mw36ea78c1_ed71_4def_96d3_857a442d7195 CRPExtracellular{liver} \n", + "23 mw147d30ec_478e_4090_b496_128a131d29eb sgp130{liver} \n", + "24 mwab41493c_6349_45f1_a226_3030cfed0e06 sR_IL6_sgp130{liver} \n", + "25 mwf405687b_7401_44ec_a0d6_4a2b35c13e8a Ab_sR{liver} \n", + "26 mw3667a5e1_02c9_44a0_acb4_b0431faa822d Ab{liver} \n", + "27 mw772cbf20_3fc1_4800_ae59_77884f1ae333 Ab_R{liver} \n", + "28 mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf Ab_sR_IL6{liver} \n", + "29 mw7becb5fe_8da8_4285_a821_0d77ad811b62 sR_IL6{gut} \n", + "30 mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca gp130{gut} \n", + "31 mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9 R_IL6_gp130{gut} \n", + "32 mw6cce2109_0e32_4dd9_98ec_41173e8ef07d Ractive{gut} \n", + "33 mw2b255f94_8018_4b99_bde8_918eeac45446 STAT3{gut} \n", + "34 mw48867e93_f170_44e8_ac7a_185b23e1bf3b pSTAT3{gut} \n", + "35 mw0083d743_836f_4238_a17f_4602193d5bc0 geneProduct{gut} \n", + "36 mwd31f52cc_04e7_40e0_885f_c7b2d9e62215 sR{gut} \n", + "37 mw2c9b0499_3325_4394_8af3_bbf653a944a0 IL6{gut} \n", + "38 mwd65b5b39_dc1b_4e77_a999_67277a880e5e sgp130{gut} \n", + "39 mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 sR_IL6_sgp130{gut} \n", + "40 mwf7796221_1fea_4274_a93e_c00adbf5778c Ab{gut} \n", + "41 mw5d764bb8_5693_4ac8_9557_f65992cc5eb0 Ab_sR{gut} \n", + "42 mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2 Ab_sR_IL6{gut} \n", + "43 mwbc2f5464_81e5_43fd_8b39_f5a2756af72f Ab{peripheral} \n", + "\n", + " original_name compartment \\\n", + "0 IL6 serum \n", + "1 sgp130 serum \n", + "2 sR_IL6_sgp130 serum \n", + "3 CRP serum \n", + "4 sR serum \n", + "5 sR_IL6 serum \n", + "6 Ab serum \n", + "7 Ab_sR serum \n", + "8 Ab_sR_IL6 serum \n", + "9 CRP Suppression (%) serum \n", + "10 CRP (% of baseline) serum \n", + "11 gp130 liver \n", + "12 R_IL6_gp130 liver \n", + "13 sR_IL6 liver \n", + "14 R liver \n", + "15 IL6 liver \n", + "16 R_IL6 liver \n", + "17 Ractive liver \n", + "18 STAT3 liver \n", + "19 pSTAT3 liver \n", + "20 CRP liver \n", + "21 sR liver \n", + "22 CRPExtracellular liver \n", + "23 sgp130 liver \n", + "24 sR_IL6_sgp130 liver \n", + "25 Ab_sR liver \n", + "26 Ab liver \n", + "27 Ab_R liver \n", + "28 Ab_sR_IL6 liver \n", + "29 sR_IL6 gut \n", + "30 gp130 gut \n", + "31 R_IL6_gp130 gut \n", + "32 Ractive gut \n", + "33 STAT3 gut \n", + "34 pSTAT3 gut \n", + "35 geneProduct gut \n", + "36 sR gut \n", + "37 IL6 gut \n", + "38 sgp130 gut \n", + "39 sR_IL6_sgp130 gut \n", + "40 Ab gut \n", + "41 Ab_sR gut \n", + "42 Ab_sR_IL6 gut \n", + "43 Ab peripheral \n", "\n", " background \\\n", - "0 Based on the provided context, IL6 (interleuki... \n", - "1 Based on the provided context, the species 'sg... \n", - "2 Based on the provided context, 'sR_IL6_sgp130'... \n", - "3 Based on the provided context, CRP, or C-react... \n", - "4 From the provided documents, there is no speci... \n", - "5 Based on the provided context and general know... \n", - "6 The context provided from the documents appear... \n", - "7 The context provided does not contain specific... \n", - "8 From the context provided, there is no direct ... \n", - "9 Based on the context provided, \"CRP Suppressio... \n", - "10 Based on the provided context and general know... \n", - "11 Gp130 is an important protein involved in the ... \n", - "12 The species named 'R_IL6_gp130', provided with... \n", - "13 The species referred to as 'sR_IL6' in the pro... \n", - "14 Based on the provided context, the document di... \n", - "15 IL-6 (Interleukin-6) is a cytokine, a type of ... \n", - "16 The context provided from the document does no... \n", - "17 The provided context does not specifically men... \n", - "18 STAT3, or Signal Transducer and Activator of T... \n", - "19 Based on the context provided, pSTAT3 is the p... \n", - "20 C-reactive protein (CRP) is a well-known marke... \n", - "21 The provided context primarily discusses the i... \n", - "22 The context provided does not specifically men... \n", - "23 Based on the provided context, sgp130 appears ... \n", - "24 Based on the context provided and general know... \n", - "25 Based on the provided context, there is no dir... \n", - "26 The species denoted as 'Ab' in the context app... \n", - "27 Based on the provided context from the documen... \n", - "28 Based on the context provided, there is no exp... \n", - "29 Based on the context provided, specific inform... \n", - "30 Gp130, also known as glycoprotein 130, is a cr... \n", - "31 Based on the context provided, it appears ther... \n", - "32 The provided context does not contain direct i... \n", - "33 STAT3, or Signal Transducer and Activator of T... \n", - "34 pSTAT3, or phosphorylated Signal Transducer an... \n", - "35 The context provided does not specifically men... \n", - "36 Based on the provided context, the species nam... \n", - "37 Based on the provided context, here is the bac... \n", - "38 sgp130, as described in the context, refers to... \n", - "39 The species 'sR_IL6_sgp130' likely refers to a... \n", - "40 Based on the provided context, there is no dir... \n", - "41 The provided context does not include specific... \n", - "42 The species \"Ab_sR_IL6\" appears to be involved... \n", - "43 The provided documents include information tha... \n", + "0 Interleukin 6 (IL-6) is a cytokine with signif... \n", + "1 The provided documents do not offer explicit i... \n", + "2 Based on the provided context and general know... \n", + "3 C-reactive protein (CRP) is an acute-phase pro... \n", + "4 The context provided from the document does no... \n", + "5 Based on the provided context, there is no spe... \n", + "6 Based on the provided context and familiar pri... \n", + "7 The document context provided does not explici... \n", + "8 The specific species 'Ab_sR_IL6{serum}' does n... \n", + "9 Based on the provided context, there is limite... \n", + "10 C-reactive protein (CRP) is an important bioma... \n", + "11 Based on the provided context and general know... \n", + "12 The species referred to as 'R_IL6_gp130{liver}... \n", + "13 The species referred to as 'sR_IL6{liver}' in ... \n", + "14 The context provided does not include specific... \n", + "15 The provided context discusses the role of IL-... \n", + "16 The provided documents mention several compone... \n", + "17 The context provided does not contain specific... \n", + "18 Based on the provided context, the specific in... \n", + "19 The context provided does not contain specific... \n", + "20 Based on the given context, there is no specif... \n", + "21 The provided context does not contain specific... \n", + "22 C-reactive protein (CRP) is an acute-phase pro... \n", + "23 The provided context does not specifically men... \n", + "24 The species 'sR_IL6_sgp130{liver}' likely repr... \n", + "25 The provided context does not specifically men... \n", + "26 Based on the provided context, there appears t... \n", + "27 The context provided does not offer specific i... \n", + "28 Based on the provided context and general scie... \n", + "29 The species referred to as 'sR_IL6{gut}' likel... \n", + "30 The context provided does not explicitly menti... \n", + "31 The context provided does not directly mention... \n", + "32 Based on the provided context, there is no spe... \n", + "33 The context provided does not include specific... \n", + "34 The provided context does not contain direct i... \n", + "35 Based on the context provided, there appears t... \n", + "36 The context provided does not contain specific... \n", + "37 Based on the context provided, IL6{gut} likely... \n", + "38 The species 'sgp130{gut}', likely derived from... \n", + "39 Based on the provided context and general know... \n", + "40 Based on the context provided and general know... \n", + "41 The context provided does not contain specific... \n", + "42 The context does not provide explicit informat... \n", + "43 The context provided does not explicitly menti... \n", "\n", " BERT_embedding \n", - "0 [[-0.38310152, 0.14221658, 0.30036777, -0.1971... \n", - "1 [[-0.39776802, 0.102813065, 0.276282, -0.17234... \n", - "2 [[-0.41926485, 0.05604683, 0.31495243, -0.0975... \n", - "3 [[-0.44731545, 0.21171626, 0.22573717, -0.1713... \n", - "4 [[-0.24422143, 0.22741008, 0.3196285, -0.20558... \n", - "5 [[-0.38647282, 0.14947572, 0.37386724, -0.2257... \n", - "6 [[-0.35710102, 0.27481169, 0.15268518, -0.2598... \n", - "7 [[-0.2979536, 0.22971633, 0.2543159, -0.238324... \n", - "8 [[-0.3250525, 0.17176488, 0.2808889, -0.207119... \n", - "9 [[-0.47315472, 0.18459623, 0.24418907, -0.1895... \n", - "10 [[-0.36008894, 0.18380362, 0.27387857, -0.2149... \n", - "11 [[-0.35777402, 0.12645116, 0.3562525, -0.23347... \n", - "12 [[-0.3070841, 0.14377351, 0.28311783, -0.18864... \n", - "13 [[-0.41398245, 0.14713271, 0.3669848, -0.26080... \n", - "14 [[-0.35146654, 0.103895366, 0.30642122, -0.249... \n", - "15 [[-0.4627117, 0.097201906, 0.3234311, -0.21945... \n", - "16 [[-0.3934079, 0.2065271, 0.28749886, -0.225543... \n", - 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" print(node_idx)\n", " \n", " node_name = nodes_list[node_idx]\n", " node = G.nodes[node_name]\n", @@ -7714,6 +1036,9 @@ " best_sim = -1\n", " \n", " for node_name in nodes_list:\n", + " # we only consider gene/protein type nodes\n", + " if (G.nodes[node_name]['type'] != 'gene/protein'):\n", + " continue\n", " curr_emb = G.nodes[node_name]['FINAL_embedding']\n", " \n", " curr_emb = curr_emb.flatten()\n", @@ -7744,592 +1069,6 @@ "species_descriptions['best_node'] = res" ] }, - { - "cell_type": "code", - "execution_count": 15, - "id": "27bee18b-e76b-43f1-9bcd-7866ffc9d394", - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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idnamebackgroundBERT_embeddingbest_node
0mwf626e95e_543f_41e4_aad4_c6bf60ab345bIL6Based on the provided context, IL6 (interleuki...[[-0.38310152, 0.14221658, 0.30036777, -0.1971...CLEC7A (Dectin-1) signaling_(62768)
1mwbbbce920_e8dd_4320_9386_fc94bfb2fc99sgp130Based on the provided context, the species 'sg...[[-0.39776802, 0.102813065, 0.276282, -0.17234...Interleukin-2 signaling_(128499)
2mw810ff751_fa4e_4143_bd50_169b3e325e1esR_IL6_sgp130Based on the provided context, 'sR_IL6_sgp130'...[[-0.41926485, 0.05604683, 0.31495243, -0.0975...Interleukin-6 signaling_(128814)
3mw114aa90f_5f5b_4fe8_9406_361c8489b6a1CRPBased on the provided context, CRP, or C-react...[[-0.44731545, 0.21171626, 0.22573717, -0.1713...Immunoregulatory interactions between a Lympho...
4mw30ae63db_6cd3_4b6f_93ad_3350cd360bccsRFrom the provided documents, there is no speci...[[-0.24422143, 0.22741008, 0.3196285, -0.20558...G alpha (12/13) signalling events_(128349)
5mw03db56ac_8dc6_4931_ae82_fef706d2ee3dsR_IL6Based on the provided context and general know...[[-0.38647282, 0.14947572, 0.37386724, -0.2257...Interleukin-6 signaling_(128814)
6mwf345ed7a_0622_403c_b816_c8749a2c9dedAbThe context provided from the documents appear...[[-0.35710102, 0.27481169, 0.15268518, -0.2598...Interleukin-2 signaling_(128499)
7mw1da111f2_a036_4392_8512_015005bdcbb7Ab_sRThe context provided does not contain specific...[[-0.2979536, 0.22971633, 0.2543159, -0.238324...Cytoprotection by HMOX1_(63064)
8mw9947742a_0e4b_4636_9a4b_b6eef2a8f6acAb_sR_IL6From the context provided, there is no direct ...[[-0.3250525, 0.17176488, 0.2808889, -0.207119...Interleukin-2 signaling_(128499)
9CRP_Suppression___CRP Suppression (%)Based on the context provided, \"CRP Suppressio...[[-0.47315472, 0.18459623, 0.24418907, -0.1895...Immunoregulatory interactions between a Lympho...
10CRP____of_baselineCRP (% of baseline)Based on the provided context and general know...[[-0.36008894, 0.18380362, 0.27387857, -0.2149...Tezacaftor_(15045)
11mw80848184_e2dd_47ce_86d7_7a21479342bdgp130Gp130 is an important protein involved in the ...[[-0.35777402, 0.12645116, 0.3562525, -0.23347...Interleukin-6 signaling_(128814)
12mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55aR_IL6_gp130The species named 'R_IL6_gp130', provided with...[[-0.3070841, 0.14377351, 0.28311783, -0.18864...CLEC7A (Dectin-1) signaling_(62768)
13mw4638f126_8cb8_4021_ab41_6ae195743ba0sR_IL6The species referred to as 'sR_IL6' in the pro...[[-0.41398245, 0.14713271, 0.3669848, -0.26080...Interleukin-6 signaling_(128814)
14mw10315fa3_6f13_4618_bda8_a8694bd3c374RBased on the provided context, the document di...[[-0.35146654, 0.103895366, 0.30642122, -0.249...Interleukin-2 signaling_(128499)
15mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1IL6IL-6 (Interleukin-6) is a cytokine, a type of ...[[-0.4627117, 0.097201906, 0.3234311, -0.21945...Interleukin-6 signaling_(128814)
16mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83R_IL6The context provided from the document does no...[[-0.3934079, 0.2065271, 0.28749886, -0.225543...CLEC7A (Dectin-1) signaling_(62768)
17mw0eb6c959_d408_45a0_a450_928b8c5876bbRactiveThe provided context does not specifically men...[[-0.24638735, 0.19071835, 0.17823611, -0.2357...The NLRP3 inflammasome_(128804)
18mw42054cd7_17af_46da_970c_7f99151906adSTAT3STAT3, or Signal Transducer and Activator of T...[[-0.3920762, 0.21867904, 0.31682876, -0.18099...MyD88:MAL(TIRAP) cascade initiated on plasma m...
19mw39c2e431_fdc3_4964_be29_6ca856620b1bpSTAT3Based on the context provided, pSTAT3 is the p...[[-0.31854075, 0.21612896, 0.36678687, -0.2491...NOD1/2 Signaling Pathway_(127908)
20mwd5313618_89eb_4c8c_bc82_66f10f966349CRPC-reactive protein (CRP) is a well-known marke...[[-0.4524013, 0.21426782, 0.26746103, -0.18231...Regulation of Complement cascade_(127866)
21mw2e464cf3_a09c_4b7c_9f3c_06720016a48esRThe provided context primarily discusses the i...[[-0.25064346, 0.32432884, 0.2525344, -0.19168...Immunoregulatory interactions between a Lympho...
22mw36ea78c1_ed71_4def_96d3_857a442d7195CRPExtracellularThe context provided does not specifically men...[[-0.35434383, 0.24616718, 0.26500684, -0.1196...Immunoregulatory interactions between a Lympho...
23mw147d30ec_478e_4090_b496_128a131d29ebsgp130Based on the provided context, sgp130 appears ...[[-0.37740308, 0.07933396, 0.32603347, -0.1108...Interleukin-6 signaling_(128814)
24mwab41493c_6349_45f1_a226_3030cfed0e06sR_IL6_sgp130Based on the context provided and general know...[[-0.37221003, 0.1744852, 0.30792367, -0.15933...Interleukin-2 signaling_(128499)
25mwf405687b_7401_44ec_a0d6_4a2b35c13e8aAb_sRBased on the provided context, there is no dir...[[-0.23842902, 0.18786879, 0.2620399, -0.21784...CLEC7A (Dectin-1) signaling_(62768)
26mw3667a5e1_02c9_44a0_acb4_b0431faa822dAbThe species denoted as 'Ab' in the context app...[[-0.52765065, 0.27688166, 0.20610718, -0.2776...Cytoprotection by HMOX1_(63064)
27mw772cbf20_3fc1_4800_ae59_77884f1ae333Ab_RBased on the provided context from the documen...[[-0.1863702, 0.36686182, 0.22280839, -0.21697...Immunoregulatory interactions between a Lympho...
28mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cfAb_sR_IL6Based on the context provided, there is no exp...[[-0.3548704, 0.1917099, 0.28657728, -0.262703...Interleukin-2 signaling_(128499)
29mw7becb5fe_8da8_4285_a821_0d77ad811b62sR_IL6Based on the context provided, specific inform...[[-0.28405702, 0.10858213, 0.32111079, -0.2300...Interleukin-2 signaling_(128499)
30mw8c9107e6_f51d_442d_b2dc_2bfdbb8482cagp130Gp130, also known as glycoprotein 130, is a cr...[[-0.47336444, 0.08036472, 0.37820706, -0.2123...Interleukin-6 signaling_(128814)
31mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9R_IL6_gp130Based on the context provided, it appears ther...[[-0.3776276, 0.21458092, 0.3001521, -0.152129...Interleukin-6 signaling_(128814)
32mw6cce2109_0e32_4dd9_98ec_41173e8ef07dRactiveThe provided context does not contain direct i...[[-0.2948512, 0.27886307, 0.23734306, -0.22463...Regulation of TLR by endogenous ligand_(127918)
33mw2b255f94_8018_4b99_bde8_918eeac45446STAT3STAT3, or Signal Transducer and Activator of T...[[-0.32530716, 0.24720953, 0.26123106, -0.2493...Growth hormone receptor signaling_(127694)
34mw48867e93_f170_44e8_ac7a_185b23e1bf3bpSTAT3pSTAT3, or phosphorylated Signal Transducer an...[[-0.37683305, 0.3004347, 0.30100918, -0.21106...Signaling by MST1_(129128)
35mw0083d743_836f_4238_a17f_4602193d5bc0geneProductThe context provided does not specifically men...[[-0.30782086, 0.2336929, 0.23015884, -0.16083...Immunoregulatory interactions between a Lympho...
36mwd31f52cc_04e7_40e0_885f_c7b2d9e62215sRBased on the provided context, the species nam...[[-0.3048136, 0.16629891, 0.3336691, -0.178628...Interleukin-2 signaling_(128499)
37mw2c9b0499_3325_4394_8af3_bbf653a944a0IL6Based on the provided context, here is the bac...[[-0.4397936, 0.15727538, 0.35291147, -0.22082...Interleukin-6 signaling_(128814)
38mwd65b5b39_dc1b_4e77_a999_67277a880e5esgp130sgp130, as described in the context, refers to...[[-0.4935615, 0.10821018, 0.1830138, -0.252587...Cytoprotection by HMOX1_(63064)
39mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3sR_IL6_sgp130The species 'sR_IL6_sgp130' likely refers to a...[[-0.2861055, 0.08323312, 0.34479225, -0.18034...Interleukin-6 signaling_(128814)
40mwf7796221_1fea_4274_a93e_c00adbf5778cAbBased on the provided context, there is no dir...[[-0.37095174, 0.32116163, 0.20662963, -0.2790...Interleukin-2 signaling_(128499)
41mw5d764bb8_5693_4ac8_9557_f65992cc5eb0Ab_sRThe provided context does not include specific...[[-0.15027289, 0.31890064, 0.17519885, -0.2029...Immunoregulatory interactions between a Lympho...
42mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2Ab_sR_IL6The species \"Ab_sR_IL6\" appears to be involved...[[-0.3795819, 0.24610856, 0.26605865, -0.28016...Interleukin-2 signaling_(128499)
43mwbc2f5464_81e5_43fd_8b39_f5a2756af72fAbThe provided documents include information tha...[[-0.46518034, 0.22024783, 0.28029412, -0.2428...Interleukin-2 signaling_(128499)
\n", - "
" - ], - "text/plain": [ - " id name \\\n", - "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 \n", - "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130 \n", - "2 mw810ff751_fa4e_4143_bd50_169b3e325e1e sR_IL6_sgp130 \n", - "3 mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 CRP \n", - "4 mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc sR \n", - "5 mw03db56ac_8dc6_4931_ae82_fef706d2ee3d sR_IL6 \n", - "6 mwf345ed7a_0622_403c_b816_c8749a2c9ded Ab \n", - "7 mw1da111f2_a036_4392_8512_015005bdcbb7 Ab_sR \n", - "8 mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac Ab_sR_IL6 \n", - "9 CRP_Suppression___ CRP Suppression (%) \n", - "10 CRP____of_baseline CRP (% of baseline) \n", - "11 mw80848184_e2dd_47ce_86d7_7a21479342bd gp130 \n", - "12 mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a R_IL6_gp130 \n", - "13 mw4638f126_8cb8_4021_ab41_6ae195743ba0 sR_IL6 \n", - "14 mw10315fa3_6f13_4618_bda8_a8694bd3c374 R \n", - "15 mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 IL6 \n", - "16 mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 R_IL6 \n", - "17 mw0eb6c959_d408_45a0_a450_928b8c5876bb Ractive \n", - "18 mw42054cd7_17af_46da_970c_7f99151906ad STAT3 \n", - "19 mw39c2e431_fdc3_4964_be29_6ca856620b1b pSTAT3 \n", - "20 mwd5313618_89eb_4c8c_bc82_66f10f966349 CRP \n", - "21 mw2e464cf3_a09c_4b7c_9f3c_06720016a48e sR \n", - "22 mw36ea78c1_ed71_4def_96d3_857a442d7195 CRPExtracellular \n", - "23 mw147d30ec_478e_4090_b496_128a131d29eb sgp130 \n", - "24 mwab41493c_6349_45f1_a226_3030cfed0e06 sR_IL6_sgp130 \n", - "25 mwf405687b_7401_44ec_a0d6_4a2b35c13e8a Ab_sR \n", - "26 mw3667a5e1_02c9_44a0_acb4_b0431faa822d Ab \n", - "27 mw772cbf20_3fc1_4800_ae59_77884f1ae333 Ab_R \n", - "28 mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf Ab_sR_IL6 \n", - "29 mw7becb5fe_8da8_4285_a821_0d77ad811b62 sR_IL6 \n", - "30 mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca gp130 \n", - "31 mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9 R_IL6_gp130 \n", - "32 mw6cce2109_0e32_4dd9_98ec_41173e8ef07d Ractive \n", - "33 mw2b255f94_8018_4b99_bde8_918eeac45446 STAT3 \n", - "34 mw48867e93_f170_44e8_ac7a_185b23e1bf3b pSTAT3 \n", - "35 mw0083d743_836f_4238_a17f_4602193d5bc0 geneProduct \n", - "36 mwd31f52cc_04e7_40e0_885f_c7b2d9e62215 sR \n", - "37 mw2c9b0499_3325_4394_8af3_bbf653a944a0 IL6 \n", - "38 mwd65b5b39_dc1b_4e77_a999_67277a880e5e sgp130 \n", - "39 mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 sR_IL6_sgp130 \n", - "40 mwf7796221_1fea_4274_a93e_c00adbf5778c Ab \n", - "41 mw5d764bb8_5693_4ac8_9557_f65992cc5eb0 Ab_sR \n", - "42 mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2 Ab_sR_IL6 \n", - "43 mwbc2f5464_81e5_43fd_8b39_f5a2756af72f Ab \n", - "\n", - " background \\\n", - "0 Based on the provided context, IL6 (interleuki... \n", - "1 Based on the provided context, the species 'sg... \n", - "2 Based on the provided context, 'sR_IL6_sgp130'... \n", - "3 Based on the provided context, CRP, or C-react... \n", - "4 From the provided documents, there is no speci... \n", - "5 Based on the provided context and general know... \n", - "6 The context provided from the documents appear... \n", - "7 The context provided does not contain specific... \n", - "8 From the context provided, there is no direct ... \n", - "9 Based on the context provided, \"CRP Suppressio... \n", - "10 Based on the provided context and general know... \n", - "11 Gp130 is an important protein involved in the ... \n", - "12 The species named 'R_IL6_gp130', provided with... \n", - "13 The species referred to as 'sR_IL6' in the pro... \n", - "14 Based on the provided context, the document di... \n", - "15 IL-6 (Interleukin-6) is a cytokine, a type of ... \n", - "16 The context provided from the document does no... \n", - "17 The provided context does not specifically men... \n", - "18 STAT3, or Signal Transducer and Activator of T... \n", - "19 Based on the context provided, pSTAT3 is the p... \n", - "20 C-reactive protein (CRP) is a well-known marke... \n", - "21 The provided context primarily discusses the i... \n", - "22 The context provided does not specifically men... \n", - "23 Based on the provided context, sgp130 appears ... \n", - "24 Based on the context provided and general know... \n", - "25 Based on the provided context, there is no dir... \n", - "26 The species denoted as 'Ab' in the context app... \n", - "27 Based on the provided context from the documen... \n", - "28 Based on the context provided, there is no exp... \n", - "29 Based on the context provided, specific inform... \n", - "30 Gp130, also known as glycoprotein 130, is a cr... \n", - "31 Based on the context provided, it appears ther... \n", - "32 The provided context does not contain direct i... \n", - "33 STAT3, or Signal Transducer and Activator of T... \n", - "34 pSTAT3, or phosphorylated Signal Transducer an... \n", - "35 The context provided does not specifically men... \n", - "36 Based on the provided context, the species nam... \n", - "37 Based on the provided context, here is the bac... \n", - "38 sgp130, as described in the context, refers to... \n", - "39 The species 'sR_IL6_sgp130' likely refers to a... \n", - "40 Based on the provided context, there is no dir... \n", - "41 The provided context does not include specific... \n", - "42 The species \"Ab_sR_IL6\" appears to be involved... \n", - "43 The provided documents include information tha... \n", - "\n", - " BERT_embedding \\\n", - "0 [[-0.38310152, 0.14221658, 0.30036777, -0.1971... \n", - "1 [[-0.39776802, 0.102813065, 0.276282, -0.17234... \n", - "2 [[-0.41926485, 0.05604683, 0.31495243, -0.0975... \n", - "3 [[-0.44731545, 0.21171626, 0.22573717, -0.1713... \n", - "4 [[-0.24422143, 0.22741008, 0.3196285, -0.20558... \n", - "5 [[-0.38647282, 0.14947572, 0.37386724, -0.2257... \n", - "6 [[-0.35710102, 0.27481169, 0.15268518, -0.2598... \n", - "7 [[-0.2979536, 0.22971633, 0.2543159, -0.238324... \n", - "8 [[-0.3250525, 0.17176488, 0.2808889, -0.207119... \n", - "9 [[-0.47315472, 0.18459623, 0.24418907, -0.1895... \n", - "10 [[-0.36008894, 0.18380362, 0.27387857, -0.2149... \n", - "11 [[-0.35777402, 0.12645116, 0.3562525, -0.23347... \n", - "12 [[-0.3070841, 0.14377351, 0.28311783, -0.18864... \n", - "13 [[-0.41398245, 0.14713271, 0.3669848, -0.26080... \n", - "14 [[-0.35146654, 0.103895366, 0.30642122, -0.249... \n", - "15 [[-0.4627117, 0.097201906, 0.3234311, -0.21945... \n", - "16 [[-0.3934079, 0.2065271, 0.28749886, -0.225543... \n", - "17 [[-0.24638735, 0.19071835, 0.17823611, -0.2357... \n", - "18 [[-0.3920762, 0.21867904, 0.31682876, -0.18099... \n", - "19 [[-0.31854075, 0.21612896, 0.36678687, -0.2491... \n", - "20 [[-0.4524013, 0.21426782, 0.26746103, -0.18231... \n", - "21 [[-0.25064346, 0.32432884, 0.2525344, -0.19168... \n", - "22 [[-0.35434383, 0.24616718, 0.26500684, -0.1196... \n", - "23 [[-0.37740308, 0.07933396, 0.32603347, -0.1108... \n", - "24 [[-0.37221003, 0.1744852, 0.30792367, -0.15933... \n", - "25 [[-0.23842902, 0.18786879, 0.2620399, -0.21784... \n", - "26 [[-0.52765065, 0.27688166, 0.20610718, -0.2776... \n", - "27 [[-0.1863702, 0.36686182, 0.22280839, -0.21697... \n", - "28 [[-0.3548704, 0.1917099, 0.28657728, -0.262703... \n", - "29 [[-0.28405702, 0.10858213, 0.32111079, -0.2300... \n", - "30 [[-0.47336444, 0.08036472, 0.37820706, -0.2123... \n", - "31 [[-0.3776276, 0.21458092, 0.3001521, -0.152129... \n", - "32 [[-0.2948512, 0.27886307, 0.23734306, -0.22463... \n", - "33 [[-0.32530716, 0.24720953, 0.26123106, -0.2493... \n", - "34 [[-0.37683305, 0.3004347, 0.30100918, -0.21106... \n", - "35 [[-0.30782086, 0.2336929, 0.23015884, -0.16083... \n", - "36 [[-0.3048136, 0.16629891, 0.3336691, -0.178628... \n", - "37 [[-0.4397936, 0.15727538, 0.35291147, -0.22082... \n", - "38 [[-0.4935615, 0.10821018, 0.1830138, -0.252587... \n", - "39 [[-0.2861055, 0.08323312, 0.34479225, -0.18034... \n", - "40 [[-0.37095174, 0.32116163, 0.20662963, -0.2790... \n", - "41 [[-0.15027289, 0.31890064, 0.17519885, -0.2029... \n", - "42 [[-0.3795819, 0.24610856, 0.26605865, -0.28016... \n", - "43 [[-0.46518034, 0.22024783, 0.28029412, -0.2428... \n", - "\n", - " best_node \n", - "0 CLEC7A (Dectin-1) signaling_(62768) \n", - "1 Interleukin-2 signaling_(128499) \n", - "2 Interleukin-6 signaling_(128814) \n", - "3 Immunoregulatory interactions between a Lympho... \n", - "4 G alpha (12/13) signalling events_(128349) \n", - "5 Interleukin-6 signaling_(128814) \n", - "6 Interleukin-2 signaling_(128499) \n", - "7 Cytoprotection by HMOX1_(63064) \n", - "8 Interleukin-2 signaling_(128499) \n", - "9 Immunoregulatory interactions between a Lympho... \n", - "10 Tezacaftor_(15045) \n", - "11 Interleukin-6 signaling_(128814) \n", - "12 CLEC7A (Dectin-1) signaling_(62768) \n", - "13 Interleukin-6 signaling_(128814) \n", - "14 Interleukin-2 signaling_(128499) \n", - "15 Interleukin-6 signaling_(128814) \n", - "16 CLEC7A (Dectin-1) signaling_(62768) \n", - "17 The NLRP3 inflammasome_(128804) \n", - "18 MyD88:MAL(TIRAP) cascade initiated on plasma m... \n", - "19 NOD1/2 Signaling Pathway_(127908) \n", - "20 Regulation of Complement cascade_(127866) \n", - "21 Immunoregulatory interactions between a Lympho... \n", - "22 Immunoregulatory interactions between a Lympho... \n", - "23 Interleukin-6 signaling_(128814) \n", - "24 Interleukin-2 signaling_(128499) \n", - "25 CLEC7A (Dectin-1) signaling_(62768) \n", - "26 Cytoprotection by HMOX1_(63064) \n", - "27 Immunoregulatory interactions between a Lympho... \n", - "28 Interleukin-2 signaling_(128499) \n", - "29 Interleukin-2 signaling_(128499) \n", - "30 Interleukin-6 signaling_(128814) \n", - "31 Interleukin-6 signaling_(128814) \n", - "32 Regulation of TLR by endogenous ligand_(127918) \n", - "33 Growth hormone receptor signaling_(127694) \n", - "34 Signaling by MST1_(129128) \n", - "35 Immunoregulatory interactions between a Lympho... \n", - "36 Interleukin-2 signaling_(128499) \n", - "37 Interleukin-6 signaling_(128814) \n", - "38 Cytoprotection by HMOX1_(63064) \n", - "39 Interleukin-6 signaling_(128814) \n", - "40 Interleukin-2 signaling_(128499) \n", - "41 Immunoregulatory interactions between a Lympho... \n", - "42 Interleukin-2 signaling_(128499) \n", - "43 Interleukin-2 signaling_(128499) " - ] - }, - "execution_count": 15, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "species_descriptions" - ] - }, { "cell_type": "markdown", "id": "a6a2d263-446c-4c38-9d02-21daa9624c02", @@ -8340,7 +1079,7 @@ }, { "cell_type": "code", - "execution_count": 18, + "execution_count": 15, "id": "98e737b2-b175-463b-9506-d4294c4138ce", "metadata": {}, "outputs": [ @@ -8369,7 +1108,7 @@ }, { "cell_type": "code", - "execution_count": 19, + "execution_count": 16, "id": "1df9bdee-b9ac-4aa6-a2df-16580930a547", "metadata": {}, "outputs": [], @@ -8390,7 +1129,7 @@ }, { "cell_type": "code", - "execution_count": 21, + "execution_count": 17, "id": "d2ab74b6-6fe2-41c8-8ca3-a2d543ba9dd5", "metadata": {}, "outputs": [], @@ -8405,7 +1144,7 @@ }, { "cell_type": "code", - "execution_count": 22, + "execution_count": 18, "id": "96db0b07-74df-4ff6-b851-a6f273d828ae", "metadata": {}, "outputs": [ @@ -8432,6 +1171,8 @@ " \n", " id\n", " name\n", + " original_name\n", + " compartment\n", " background\n", " BERT_embedding\n", " best_node\n", @@ -8442,590 +1183,678 @@ " \n", " 0\n", " mwf626e95e_543f_41e4_aad4_c6bf60ab345b\n", + " IL6{serum}\n", " IL6\n", - " Based on the provided context, IL6 (interleuki...\n", - " [[-0.38310152, 0.14221658, 0.30036777, -0.1971...\n", - " CLEC7A (Dectin-1) signaling_(62768)\n", - " R-HSA-5607764\n", + " serum\n", + " Interleukin 6 (IL-6) is a cytokine with signif...\n", + " [[-0.36046556, 0.1984801, 0.34831223, -0.13759...\n", + " CXCL8_(2978)\n", + " 3576\n", " \n", " \n", " 1\n", " mwbbbce920_e8dd_4320_9386_fc94bfb2fc99\n", + " sgp130{serum}\n", " sgp130\n", - " Based on the provided context, the species 'sg...\n", - " [[-0.39776802, 0.102813065, 0.276282, -0.17234...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " serum\n", + " The provided documents do not offer explicit i...\n", + " [[-0.33606362, 0.14078653, 0.28409472, -0.1816...\n", + " IL2RA_(7059)\n", + " 3559\n", " \n", " \n", " 2\n", " mw810ff751_fa4e_4143_bd50_169b3e325e1e\n", + " sR_IL6_sgp130{serum}\n", " sR_IL6_sgp130\n", - " Based on the provided context, 'sR_IL6_sgp130'...\n", - " [[-0.41926485, 0.05604683, 0.31495243, -0.0975...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " serum\n", + " Based on the provided context and general know...\n", + " [[-0.35146952, 0.10439779, 0.35805824, -0.1242...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 3\n", " mw114aa90f_5f5b_4fe8_9406_361c8489b6a1\n", + " CRP{serum}\n", " CRP\n", - " Based on the provided context, CRP, or C-react...\n", - " [[-0.44731545, 0.21171626, 0.22573717, -0.1713...\n", - " Immunoregulatory interactions between a Lympho...\n", - " R-HSA-198933\n", + " serum\n", + " C-reactive protein (CRP) is an acute-phase pro...\n", + " [[-0.51451033, 0.34030703, 0.27825356, -0.1979...\n", + " CXCL8_(2978)\n", + " 3576\n", " \n", " \n", " 4\n", " mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc\n", + " sR{serum}\n", " sR\n", - " From the provided documents, there is no speci...\n", - " [[-0.24422143, 0.22741008, 0.3196285, -0.20558...\n", - " G alpha (12/13) signalling events_(128349)\n", - " R-HSA-416482\n", + " serum\n", + " The context provided from the document does no...\n", + " [[-0.19817938, 0.3326699, 0.28404108, -0.11455...\n", + " CRP_(2384)\n", + " 1401\n", " \n", " \n", " 5\n", " mw03db56ac_8dc6_4931_ae82_fef706d2ee3d\n", + " sR_IL6{serum}\n", " sR_IL6\n", - " Based on the provided context and general know...\n", - " [[-0.38647282, 0.14947572, 0.37386724, -0.2257...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " serum\n", + " Based on the provided context, there is no spe...\n", + " [[-0.38143575, 0.16730621, 0.33593783, -0.1761...\n", + " IL2RA_(7059)\n", + " 3559\n", " \n", " \n", " 6\n", " mwf345ed7a_0622_403c_b816_c8749a2c9ded\n", + " Ab{serum}\n", " Ab\n", - " The context provided from the documents appear...\n", - " [[-0.35710102, 0.27481169, 0.15268518, -0.2598...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " serum\n", + " Based on the provided context and familiar pri...\n", + " [[-0.26659864, 0.37297052, 0.12752607, -0.0740...\n", + " CRP_(2384)\n", + " 1401\n", " \n", " \n", " 7\n", " mw1da111f2_a036_4392_8512_015005bdcbb7\n", + " Ab_sR{serum}\n", " Ab_sR\n", - " The context provided does not contain specific...\n", - " [[-0.2979536, 0.22971633, 0.2543159, -0.238324...\n", - " Cytoprotection by HMOX1_(63064)\n", - " R-HSA-9707564\n", + " serum\n", + " The document context provided does not explici...\n", + " [[-0.25748405, 0.3326551, 0.22365786, -0.12952...\n", + " CRP_(2384)\n", + " 1401\n", " \n", " \n", " 8\n", " mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac\n", + " Ab_sR_IL6{serum}\n", " Ab_sR_IL6\n", - " From the context provided, there is no direct ...\n", - " [[-0.3250525, 0.17176488, 0.2808889, -0.207119...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " serum\n", + " The specific species 'Ab_sR_IL6{serum}' does n...\n", + " [[-0.37747848, 0.26106745, 0.29221672, -0.1456...\n", + " IL2RA_(7059)\n", + " 3559\n", " \n", " \n", " 9\n", " CRP_Suppression___\n", + " CRP Suppression (%){serum}\n", " CRP Suppression (%)\n", - " Based on the context provided, \"CRP Suppressio...\n", - " [[-0.47315472, 0.18459623, 0.24418907, -0.1895...\n", - " Immunoregulatory interactions between a Lympho...\n", - " R-HSA-198933\n", + " serum\n", + " Based on the provided context, there is limite...\n", + " [[-0.4193665, 0.19158283, 0.2804547, -0.165872...\n", + " IL2RA_(7059)\n", + " 3559\n", " \n", " \n", " 10\n", " CRP____of_baseline\n", + " CRP (% of baseline){serum}\n", " CRP (% of baseline)\n", - " Based on the provided context and general know...\n", - " [[-0.36008894, 0.18380362, 0.27387857, -0.2149...\n", - " Tezacaftor_(15045)\n", - " DB11712\n", + " serum\n", + " C-reactive protein (CRP) is an important bioma...\n", + " [[-0.39912638, 0.23087408, 0.27915168, -0.1415...\n", + " CRP_(2384)\n", + " 1401\n", " \n", " \n", " 11\n", " mw80848184_e2dd_47ce_86d7_7a21479342bd\n", + " gp130{liver}\n", " gp130\n", - " Gp130 is an important protein involved in the ...\n", - " [[-0.35777402, 0.12645116, 0.3562525, -0.23347...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " liver\n", + " Based on the provided context and general know...\n", + " [[-0.33445, 0.23918422, 0.2927546, -0.17028718...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 12\n", " mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a\n", + " R_IL6_gp130{liver}\n", " R_IL6_gp130\n", - " The species named 'R_IL6_gp130', provided with...\n", - " [[-0.3070841, 0.14377351, 0.28311783, -0.18864...\n", - " CLEC7A (Dectin-1) signaling_(62768)\n", - " R-HSA-5607764\n", + " liver\n", + " The species referred to as 'R_IL6_gp130{liver}...\n", + " [[-0.40478626, 0.17814767, 0.27589074, -0.1340...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 13\n", " mw4638f126_8cb8_4021_ab41_6ae195743ba0\n", + " sR_IL6{liver}\n", " sR_IL6\n", - " The species referred to as 'sR_IL6' in the pro...\n", - " [[-0.41398245, 0.14713271, 0.3669848, -0.26080...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " liver\n", + " The species referred to as 'sR_IL6{liver}' in ...\n", + " [[-0.45756304, 0.17891681, 0.36423725, -0.2334...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 14\n", " mw10315fa3_6f13_4618_bda8_a8694bd3c374\n", + " R{liver}\n", " R\n", - " Based on the provided context, the document di...\n", - " [[-0.35146654, 0.103895366, 0.30642122, -0.249...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " liver\n", + " The context provided does not include specific...\n", + " [[-0.4199063, 0.25244138, 0.23973583, -0.12047...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 15\n", " mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1\n", + " IL6{liver}\n", " IL6\n", - " IL-6 (Interleukin-6) is a cytokine, a type of ...\n", - " [[-0.4627117, 0.097201906, 0.3234311, -0.21945...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " liver\n", + " The provided context discusses the role of IL-...\n", + " [[-0.5299805, 0.20470381, 0.21622677, -0.16921...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 16\n", " mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83\n", + " R_IL6{liver}\n", " R_IL6\n", - " The context provided from the document does no...\n", - " [[-0.3934079, 0.2065271, 0.28749886, -0.225543...\n", - " CLEC7A (Dectin-1) signaling_(62768)\n", - " R-HSA-5607764\n", + " liver\n", + " The provided documents mention several compone...\n", + " [[-0.40827248, 0.1906287, 0.36825097, -0.23810...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 17\n", " mw0eb6c959_d408_45a0_a450_928b8c5876bb\n", + " Ractive{liver}\n", " Ractive\n", - " The provided context does not specifically men...\n", - " [[-0.24638735, 0.19071835, 0.17823611, -0.2357...\n", - " The NLRP3 inflammasome_(128804)\n", - " R-HSA-844456\n", + " liver\n", + " The context provided does not contain specific...\n", + " [[-0.29601544, 0.32257238, 0.11635402, -0.1388...\n", + " MMP9_(3474)\n", + " 4318\n", " \n", " \n", " 18\n", " mw42054cd7_17af_46da_970c_7f99151906ad\n", + " STAT3{liver}\n", " STAT3\n", - " STAT3, or Signal Transducer and Activator of T...\n", - " [[-0.3920762, 0.21867904, 0.31682876, -0.18099...\n", - " MyD88:MAL(TIRAP) cascade initiated on plasma m...\n", - " R-HSA-166058\n", + " liver\n", + " Based on the provided context, the specific in...\n", + " [[-0.48407704, 0.26490304, 0.2329331, -0.23542...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 19\n", " mw39c2e431_fdc3_4964_be29_6ca856620b1b\n", + " pSTAT3{liver}\n", " pSTAT3\n", - " Based on the context provided, pSTAT3 is the p...\n", - " [[-0.31854075, 0.21612896, 0.36678687, -0.2491...\n", - " NOD1/2 Signaling Pathway_(127908)\n", - " R-HSA-168638\n", + " liver\n", + " The context provided does not contain specific...\n", + " [[-0.31865203, 0.20982854, 0.33414608, -0.1467...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 20\n", " mwd5313618_89eb_4c8c_bc82_66f10f966349\n", + " CRP{liver}\n", " CRP\n", - " C-reactive protein (CRP) is a well-known marke...\n", - " [[-0.4524013, 0.21426782, 0.26746103, -0.18231...\n", - " Regulation of Complement cascade_(127866)\n", - " R-HSA-977606\n", + " liver\n", + " Based on the given context, there is no specif...\n", + " [[-0.28650454, 0.28451994, 0.22697207, -0.1883...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 21\n", " mw2e464cf3_a09c_4b7c_9f3c_06720016a48e\n", + " sR{liver}\n", " sR\n", - " The provided context primarily discusses the i...\n", - " [[-0.25064346, 0.32432884, 0.2525344, -0.19168...\n", - " Immunoregulatory interactions between a Lympho...\n", - " R-HSA-198933\n", + " liver\n", + " The provided context does not contain specific...\n", + " [[-0.3657858, 0.18391879, 0.26731104, -0.14256...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 22\n", " mw36ea78c1_ed71_4def_96d3_857a442d7195\n", + " CRPExtracellular{liver}\n", " CRPExtracellular\n", - " The context provided does not specifically men...\n", - " [[-0.35434383, 0.24616718, 0.26500684, -0.1196...\n", - " Immunoregulatory interactions between a Lympho...\n", - " R-HSA-198933\n", + " liver\n", + " C-reactive protein (CRP) is an acute-phase pro...\n", + " [[-0.52379715, 0.26640716, 0.24741346, -0.2049...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 23\n", " mw147d30ec_478e_4090_b496_128a131d29eb\n", + " sgp130{liver}\n", " sgp130\n", - " Based on the provided context, sgp130 appears ...\n", - " [[-0.37740308, 0.07933396, 0.32603347, -0.1108...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " liver\n", + " The provided context does not specifically men...\n", + " [[-0.41315806, 0.19693111, 0.18671003, -0.1230...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 24\n", " mwab41493c_6349_45f1_a226_3030cfed0e06\n", + " sR_IL6_sgp130{liver}\n", " sR_IL6_sgp130\n", - " Based on the context provided and general know...\n", - " [[-0.37221003, 0.1744852, 0.30792367, -0.15933...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " liver\n", + " The species 'sR_IL6_sgp130{liver}' likely repr...\n", + " [[-0.43109208, 0.25532103, 0.27182448, -0.1714...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 25\n", " mwf405687b_7401_44ec_a0d6_4a2b35c13e8a\n", + " Ab_sR{liver}\n", " Ab_sR\n", - " Based on the provided context, there is no dir...\n", - " [[-0.23842902, 0.18786879, 0.2620399, -0.21784...\n", - " CLEC7A (Dectin-1) signaling_(62768)\n", - " R-HSA-5607764\n", + " liver\n", + " The provided context does not specifically men...\n", + " [[-0.31681302, 0.38205892, 0.13448949, -0.1530...\n", + " CRP_(2384)\n", + " 1401\n", " \n", " \n", " 26\n", " mw3667a5e1_02c9_44a0_acb4_b0431faa822d\n", + " Ab{liver}\n", " Ab\n", - " The species denoted as 'Ab' in the context app...\n", - " [[-0.52765065, 0.27688166, 0.20610718, -0.2776...\n", - " Cytoprotection by HMOX1_(63064)\n", - " R-HSA-9707564\n", + " liver\n", + " Based on the provided context, there appears t...\n", + " [[-0.25571656, 0.41298026, 0.169575, -0.146192...\n", + " CRP_(2384)\n", + " 1401\n", " \n", " \n", " 27\n", " mw772cbf20_3fc1_4800_ae59_77884f1ae333\n", + " Ab_R{liver}\n", " Ab_R\n", - " Based on the provided context from the documen...\n", - " [[-0.1863702, 0.36686182, 0.22280839, -0.21697...\n", - " Immunoregulatory interactions between a Lympho...\n", - " R-HSA-198933\n", + " liver\n", + " The context provided does not offer specific i...\n", + " [[-0.2570913, 0.29179507, 0.19184656, -0.14854...\n", + " CRP_(2384)\n", + " 1401\n", " \n", " \n", " 28\n", " mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf\n", + " Ab_sR_IL6{liver}\n", " Ab_sR_IL6\n", - " Based on the context provided, there is no exp...\n", - " [[-0.3548704, 0.1917099, 0.28657728, -0.262703...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " liver\n", + " Based on the provided context and general scie...\n", + " [[-0.3885418, 0.18170443, 0.34147617, -0.20549...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 29\n", " mw7becb5fe_8da8_4285_a821_0d77ad811b62\n", + " sR_IL6{gut}\n", " sR_IL6\n", - " Based on the context provided, specific inform...\n", - " [[-0.28405702, 0.10858213, 0.32111079, -0.2300...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " gut\n", + " The species referred to as 'sR_IL6{gut}' likel...\n", + " [[-0.4339128, 0.22657649, 0.25634766, -0.19923...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 30\n", " mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca\n", + " gp130{gut}\n", " gp130\n", - " Gp130, also known as glycoprotein 130, is a cr...\n", - " [[-0.47336444, 0.08036472, 0.37820706, -0.2123...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " gut\n", + " The context provided does not explicitly menti...\n", + " [[-0.39961886, 0.21250604, 0.20553315, -0.1531...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 31\n", " mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9\n", + " R_IL6_gp130{gut}\n", " R_IL6_gp130\n", - " Based on the context provided, it appears ther...\n", - " [[-0.3776276, 0.21458092, 0.3001521, -0.152129...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " gut\n", + " The context provided does not directly mention...\n", + " [[-0.4055007, 0.20729655, 0.2815721, -0.172021...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 32\n", " mw6cce2109_0e32_4dd9_98ec_41173e8ef07d\n", + " Ractive{gut}\n", " Ractive\n", - " The provided context does not contain direct i...\n", - " [[-0.2948512, 0.27886307, 0.23734306, -0.22463...\n", - " Regulation of TLR by endogenous ligand_(127918)\n", - " R-HSA-5686938\n", + " gut\n", + " Based on the provided context, there is no spe...\n", + " [[-0.19464502, 0.30159003, 0.034058932, -0.134...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 33\n", " mw2b255f94_8018_4b99_bde8_918eeac45446\n", + " STAT3{gut}\n", " STAT3\n", - " STAT3, or Signal Transducer and Activator of T...\n", - " [[-0.32530716, 0.24720953, 0.26123106, -0.2493...\n", - " Growth hormone receptor signaling_(127694)\n", - " R-HSA-982772\n", + " gut\n", + " The context provided does not include specific...\n", + " [[-0.3604745, 0.23800118, 0.19214159, -0.21026...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 34\n", " mw48867e93_f170_44e8_ac7a_185b23e1bf3b\n", + " pSTAT3{gut}\n", " pSTAT3\n", - " pSTAT3, or phosphorylated Signal Transducer an...\n", - " [[-0.37683305, 0.3004347, 0.30100918, -0.21106...\n", - " Signaling by MST1_(129128)\n", - " R-HSA-8852405\n", + " gut\n", + " The provided context does not contain direct i...\n", + " [[-0.41001073, 0.18395737, 0.21566965, -0.1557...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 35\n", " mw0083d743_836f_4238_a17f_4602193d5bc0\n", + " geneProduct{gut}\n", " geneProduct\n", - " The context provided does not specifically men...\n", - " [[-0.30782086, 0.2336929, 0.23015884, -0.16083...\n", - " Immunoregulatory interactions between a Lympho...\n", - " R-HSA-198933\n", + " gut\n", + " Based on the context provided, there appears t...\n", + " [[-0.1892068, 0.32208663, 0.13539186, -0.07255...\n", + " MMP9_(3474)\n", + " 4318\n", " \n", " \n", " 36\n", " mwd31f52cc_04e7_40e0_885f_c7b2d9e62215\n", + " sR{gut}\n", " sR\n", - " Based on the provided context, the species nam...\n", - " [[-0.3048136, 0.16629891, 0.3336691, -0.178628...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " gut\n", + " The context provided does not contain specific...\n", + " [[-0.366351, 0.21531877, 0.2917647, -0.1173586...\n", + " CRP_(2384)\n", + " 1401\n", " \n", " \n", " 37\n", " mw2c9b0499_3325_4394_8af3_bbf653a944a0\n", + " IL6{gut}\n", " IL6\n", - " Based on the provided context, here is the bac...\n", - " [[-0.4397936, 0.15727538, 0.35291147, -0.22082...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " gut\n", + " Based on the context provided, IL6{gut} likely...\n", + " [[-0.38345662, 0.14892936, 0.283594, -0.155339...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 38\n", " mwd65b5b39_dc1b_4e77_a999_67277a880e5e\n", + " sgp130{gut}\n", " sgp130\n", - " sgp130, as described in the context, refers to...\n", - " [[-0.4935615, 0.10821018, 0.1830138, -0.252587...\n", - " Cytoprotection by HMOX1_(63064)\n", - " R-HSA-9707564\n", + " gut\n", + " The species 'sgp130{gut}', likely derived from...\n", + " [[-0.44768405, 0.19976878, 0.17069031, -0.1916...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 39\n", " mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3\n", + " sR_IL6_sgp130{gut}\n", " sR_IL6_sgp130\n", - " The species 'sR_IL6_sgp130' likely refers to a...\n", - " [[-0.2861055, 0.08323312, 0.34479225, -0.18034...\n", - " Interleukin-6 signaling_(128814)\n", - " R-HSA-1059683\n", + " gut\n", + " Based on the provided context and general know...\n", + " [[-0.45934308, 0.19494462, 0.22395587, -0.1774...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 40\n", " mwf7796221_1fea_4274_a93e_c00adbf5778c\n", + " Ab{gut}\n", " Ab\n", - " Based on the provided context, there is no dir...\n", - " [[-0.37095174, 0.32116163, 0.20662963, -0.2790...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " gut\n", + " Based on the context provided and general know...\n", + " [[-0.3002606, 0.34374207, 0.15582994, -0.14586...\n", + " CXCL8_(2978)\n", + " 3576\n", " \n", " \n", " 41\n", " mw5d764bb8_5693_4ac8_9557_f65992cc5eb0\n", + " Ab_sR{gut}\n", " Ab_sR\n", - " The provided context does not include specific...\n", - " [[-0.15027289, 0.31890064, 0.17519885, -0.2029...\n", - " Immunoregulatory interactions between a Lympho...\n", - " R-HSA-198933\n", + " gut\n", + " The context provided does not contain specific...\n", + " [[-0.3193748, 0.24593732, 0.22288847, -0.09116...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 42\n", " mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2\n", + " Ab_sR_IL6{gut}\n", " Ab_sR_IL6\n", - " The species \"Ab_sR_IL6\" appears to be involved...\n", - " [[-0.3795819, 0.24610856, 0.26605865, -0.28016...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " gut\n", + " The context does not provide explicit informat...\n", + " [[-0.44073004, 0.20752984, 0.22041091, -0.1554...\n", + " IL1B_(1004)\n", + " 3553\n", " \n", " \n", " 43\n", " mwbc2f5464_81e5_43fd_8b39_f5a2756af72f\n", + " Ab{peripheral}\n", " Ab\n", - " The provided documents include information tha...\n", - " [[-0.46518034, 0.22024783, 0.28029412, -0.2428...\n", - " Interleukin-2 signaling_(128499)\n", - " R-HSA-9020558\n", + " peripheral\n", + " The context provided does not explicitly menti...\n", + " [[-0.15118778, 0.33757055, 0.18688324, -0.0879...\n", + " CRP_(2384)\n", + " 1401\n", " \n", " \n", "\n", "" ], "text/plain": [ - " id name \\\n", - "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6 \n", - "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130 \n", - "2 mw810ff751_fa4e_4143_bd50_169b3e325e1e sR_IL6_sgp130 \n", - "3 mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 CRP \n", - "4 mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc sR \n", - "5 mw03db56ac_8dc6_4931_ae82_fef706d2ee3d sR_IL6 \n", - "6 mwf345ed7a_0622_403c_b816_c8749a2c9ded Ab \n", - "7 mw1da111f2_a036_4392_8512_015005bdcbb7 Ab_sR \n", - "8 mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac Ab_sR_IL6 \n", - "9 CRP_Suppression___ CRP Suppression (%) \n", - "10 CRP____of_baseline CRP (% of baseline) \n", - "11 mw80848184_e2dd_47ce_86d7_7a21479342bd gp130 \n", - "12 mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a R_IL6_gp130 \n", - "13 mw4638f126_8cb8_4021_ab41_6ae195743ba0 sR_IL6 \n", - "14 mw10315fa3_6f13_4618_bda8_a8694bd3c374 R \n", - "15 mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 IL6 \n", - "16 mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 R_IL6 \n", - "17 mw0eb6c959_d408_45a0_a450_928b8c5876bb Ractive \n", - "18 mw42054cd7_17af_46da_970c_7f99151906ad STAT3 \n", - "19 mw39c2e431_fdc3_4964_be29_6ca856620b1b pSTAT3 \n", - "20 mwd5313618_89eb_4c8c_bc82_66f10f966349 CRP \n", - "21 mw2e464cf3_a09c_4b7c_9f3c_06720016a48e sR \n", - "22 mw36ea78c1_ed71_4def_96d3_857a442d7195 CRPExtracellular \n", - "23 mw147d30ec_478e_4090_b496_128a131d29eb sgp130 \n", - "24 mwab41493c_6349_45f1_a226_3030cfed0e06 sR_IL6_sgp130 \n", - "25 mwf405687b_7401_44ec_a0d6_4a2b35c13e8a Ab_sR \n", - "26 mw3667a5e1_02c9_44a0_acb4_b0431faa822d Ab \n", - "27 mw772cbf20_3fc1_4800_ae59_77884f1ae333 Ab_R \n", - "28 mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf Ab_sR_IL6 \n", - "29 mw7becb5fe_8da8_4285_a821_0d77ad811b62 sR_IL6 \n", - "30 mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca gp130 \n", - "31 mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9 R_IL6_gp130 \n", - "32 mw6cce2109_0e32_4dd9_98ec_41173e8ef07d Ractive \n", - "33 mw2b255f94_8018_4b99_bde8_918eeac45446 STAT3 \n", - "34 mw48867e93_f170_44e8_ac7a_185b23e1bf3b pSTAT3 \n", - "35 mw0083d743_836f_4238_a17f_4602193d5bc0 geneProduct \n", - "36 mwd31f52cc_04e7_40e0_885f_c7b2d9e62215 sR \n", - "37 mw2c9b0499_3325_4394_8af3_bbf653a944a0 IL6 \n", - "38 mwd65b5b39_dc1b_4e77_a999_67277a880e5e sgp130 \n", - "39 mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 sR_IL6_sgp130 \n", - "40 mwf7796221_1fea_4274_a93e_c00adbf5778c Ab \n", - "41 mw5d764bb8_5693_4ac8_9557_f65992cc5eb0 Ab_sR \n", - "42 mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2 Ab_sR_IL6 \n", - "43 mwbc2f5464_81e5_43fd_8b39_f5a2756af72f Ab \n", + " id name \\\n", + "0 mwf626e95e_543f_41e4_aad4_c6bf60ab345b IL6{serum} \n", + "1 mwbbbce920_e8dd_4320_9386_fc94bfb2fc99 sgp130{serum} \n", + "2 mw810ff751_fa4e_4143_bd50_169b3e325e1e sR_IL6_sgp130{serum} \n", + "3 mw114aa90f_5f5b_4fe8_9406_361c8489b6a1 CRP{serum} \n", + "4 mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc sR{serum} \n", + "5 mw03db56ac_8dc6_4931_ae82_fef706d2ee3d sR_IL6{serum} \n", + "6 mwf345ed7a_0622_403c_b816_c8749a2c9ded Ab{serum} \n", + "7 mw1da111f2_a036_4392_8512_015005bdcbb7 Ab_sR{serum} \n", + "8 mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac Ab_sR_IL6{serum} \n", + "9 CRP_Suppression___ CRP Suppression (%){serum} \n", + "10 CRP____of_baseline CRP (% of baseline){serum} \n", + "11 mw80848184_e2dd_47ce_86d7_7a21479342bd gp130{liver} \n", + "12 mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a R_IL6_gp130{liver} \n", + "13 mw4638f126_8cb8_4021_ab41_6ae195743ba0 sR_IL6{liver} \n", + "14 mw10315fa3_6f13_4618_bda8_a8694bd3c374 R{liver} \n", + "15 mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1 IL6{liver} \n", + "16 mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83 R_IL6{liver} \n", + "17 mw0eb6c959_d408_45a0_a450_928b8c5876bb Ractive{liver} \n", + "18 mw42054cd7_17af_46da_970c_7f99151906ad STAT3{liver} \n", + "19 mw39c2e431_fdc3_4964_be29_6ca856620b1b pSTAT3{liver} \n", + "20 mwd5313618_89eb_4c8c_bc82_66f10f966349 CRP{liver} \n", + "21 mw2e464cf3_a09c_4b7c_9f3c_06720016a48e sR{liver} \n", + "22 mw36ea78c1_ed71_4def_96d3_857a442d7195 CRPExtracellular{liver} \n", + "23 mw147d30ec_478e_4090_b496_128a131d29eb sgp130{liver} \n", + "24 mwab41493c_6349_45f1_a226_3030cfed0e06 sR_IL6_sgp130{liver} \n", + "25 mwf405687b_7401_44ec_a0d6_4a2b35c13e8a Ab_sR{liver} \n", + "26 mw3667a5e1_02c9_44a0_acb4_b0431faa822d Ab{liver} \n", + "27 mw772cbf20_3fc1_4800_ae59_77884f1ae333 Ab_R{liver} \n", + "28 mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf Ab_sR_IL6{liver} \n", + "29 mw7becb5fe_8da8_4285_a821_0d77ad811b62 sR_IL6{gut} \n", + "30 mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca gp130{gut} \n", + "31 mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9 R_IL6_gp130{gut} \n", + "32 mw6cce2109_0e32_4dd9_98ec_41173e8ef07d Ractive{gut} \n", + "33 mw2b255f94_8018_4b99_bde8_918eeac45446 STAT3{gut} \n", + "34 mw48867e93_f170_44e8_ac7a_185b23e1bf3b pSTAT3{gut} \n", + "35 mw0083d743_836f_4238_a17f_4602193d5bc0 geneProduct{gut} \n", + "36 mwd31f52cc_04e7_40e0_885f_c7b2d9e62215 sR{gut} \n", + "37 mw2c9b0499_3325_4394_8af3_bbf653a944a0 IL6{gut} \n", + "38 mwd65b5b39_dc1b_4e77_a999_67277a880e5e sgp130{gut} \n", + "39 mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3 sR_IL6_sgp130{gut} \n", + "40 mwf7796221_1fea_4274_a93e_c00adbf5778c Ab{gut} \n", + "41 mw5d764bb8_5693_4ac8_9557_f65992cc5eb0 Ab_sR{gut} \n", + "42 mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2 Ab_sR_IL6{gut} \n", + "43 mwbc2f5464_81e5_43fd_8b39_f5a2756af72f Ab{peripheral} \n", "\n", - " background \\\n", - "0 Based on the provided context, IL6 (interleuki... \n", - "1 Based on the provided context, the species 'sg... \n", - "2 Based on the provided context, 'sR_IL6_sgp130'... \n", - "3 Based on the provided context, CRP, or C-react... \n", - "4 From the provided documents, there is no speci... \n", - "5 Based on the provided context and general know... \n", - "6 The context provided from the documents appear... \n", - "7 The context provided does not contain specific... \n", - "8 From the context provided, there is no direct ... \n", - "9 Based on the context provided, \"CRP Suppressio... \n", - "10 Based on the provided context and general know... \n", - "11 Gp130 is an important protein involved in the ... \n", - "12 The species named 'R_IL6_gp130', provided with... \n", - "13 The species referred to as 'sR_IL6' in the pro... \n", - "14 Based on the provided context, the document di... \n", - "15 IL-6 (Interleukin-6) is a cytokine, a type of ... \n", - "16 The context provided from the document does no... \n", - "17 The provided context does not specifically men... \n", - "18 STAT3, or Signal Transducer and Activator of T... \n", - "19 Based on the context provided, pSTAT3 is the p... \n", - "20 C-reactive protein (CRP) is a well-known marke... \n", - "21 The provided context primarily discusses the i... \n", - "22 The context provided does not specifically men... \n", - "23 Based on the provided context, sgp130 appears ... \n", - "24 Based on the context provided and general know... \n", - "25 Based on the provided context, there is no dir... \n", - "26 The species denoted as 'Ab' in the context app... \n", - "27 Based on the provided context from the documen... \n", - "28 Based on the context provided, there is no exp... \n", - "29 Based on the context provided, specific inform... \n", - "30 Gp130, also known as glycoprotein 130, is a cr... \n", - "31 Based on the context provided, it appears ther... \n", - "32 The provided context does not contain direct i... \n", - "33 STAT3, or Signal Transducer and Activator of T... \n", - "34 pSTAT3, or phosphorylated Signal Transducer an... \n", - "35 The context provided does not specifically men... \n", - "36 Based on the provided context, the species nam... \n", - "37 Based on the provided context, here is the bac... \n", - "38 sgp130, as described in the context, refers to... \n", - "39 The species 'sR_IL6_sgp130' likely refers to a... \n", - "40 Based on the provided context, there is no dir... \n", - "41 The provided context does not include specific... \n", - "42 The species \"Ab_sR_IL6\" appears to be involved... \n", - "43 The provided documents include information tha... \n", + " original_name compartment \\\n", + "0 IL6 serum \n", + "1 sgp130 serum \n", + "2 sR_IL6_sgp130 serum \n", + "3 CRP serum \n", + "4 sR serum \n", + "5 sR_IL6 serum \n", + "6 Ab serum \n", + "7 Ab_sR serum \n", + "8 Ab_sR_IL6 serum \n", + "9 CRP Suppression (%) serum \n", + "10 CRP (% of baseline) serum \n", + "11 gp130 liver \n", + "12 R_IL6_gp130 liver \n", + "13 sR_IL6 liver \n", + "14 R liver \n", + "15 IL6 liver \n", + "16 R_IL6 liver \n", + "17 Ractive liver \n", + "18 STAT3 liver \n", + "19 pSTAT3 liver \n", + "20 CRP liver \n", + "21 sR liver \n", + "22 CRPExtracellular liver \n", + "23 sgp130 liver \n", + "24 sR_IL6_sgp130 liver \n", + "25 Ab_sR liver \n", + "26 Ab liver \n", + "27 Ab_R liver \n", + "28 Ab_sR_IL6 liver \n", + "29 sR_IL6 gut \n", + "30 gp130 gut \n", + "31 R_IL6_gp130 gut \n", + "32 Ractive gut \n", + "33 STAT3 gut \n", + "34 pSTAT3 gut \n", + "35 geneProduct gut \n", + "36 sR gut \n", + "37 IL6 gut \n", + "38 sgp130 gut \n", + "39 sR_IL6_sgp130 gut \n", + "40 Ab gut \n", + "41 Ab_sR gut \n", + "42 Ab_sR_IL6 gut \n", + "43 Ab peripheral \n", "\n", - " BERT_embedding \\\n", - "0 [[-0.38310152, 0.14221658, 0.30036777, -0.1971... \n", - "1 [[-0.39776802, 0.102813065, 0.276282, -0.17234... \n", - "2 [[-0.41926485, 0.05604683, 0.31495243, -0.0975... \n", - "3 [[-0.44731545, 0.21171626, 0.22573717, -0.1713... \n", - "4 [[-0.24422143, 0.22741008, 0.3196285, -0.20558... \n", - "5 [[-0.38647282, 0.14947572, 0.37386724, -0.2257... \n", - "6 [[-0.35710102, 0.27481169, 0.15268518, -0.2598... \n", - "7 [[-0.2979536, 0.22971633, 0.2543159, -0.238324... \n", - "8 [[-0.3250525, 0.17176488, 0.2808889, -0.207119... \n", - "9 [[-0.47315472, 0.18459623, 0.24418907, -0.1895... \n", - "10 [[-0.36008894, 0.18380362, 0.27387857, -0.2149... \n", - "11 [[-0.35777402, 0.12645116, 0.3562525, -0.23347... \n", - "12 [[-0.3070841, 0.14377351, 0.28311783, -0.18864... \n", - "13 [[-0.41398245, 0.14713271, 0.3669848, -0.26080... \n", - "14 [[-0.35146654, 0.103895366, 0.30642122, -0.249... \n", - "15 [[-0.4627117, 0.097201906, 0.3234311, -0.21945... \n", - "16 [[-0.3934079, 0.2065271, 0.28749886, -0.225543... \n", - "17 [[-0.24638735, 0.19071835, 0.17823611, -0.2357... \n", - "18 [[-0.3920762, 0.21867904, 0.31682876, -0.18099... \n", - "19 [[-0.31854075, 0.21612896, 0.36678687, -0.2491... \n", - "20 [[-0.4524013, 0.21426782, 0.26746103, -0.18231... \n", - "21 [[-0.25064346, 0.32432884, 0.2525344, -0.19168... \n", - "22 [[-0.35434383, 0.24616718, 0.26500684, -0.1196... \n", - "23 [[-0.37740308, 0.07933396, 0.32603347, -0.1108... \n", - "24 [[-0.37221003, 0.1744852, 0.30792367, -0.15933... \n", - "25 [[-0.23842902, 0.18786879, 0.2620399, -0.21784... \n", - "26 [[-0.52765065, 0.27688166, 0.20610718, -0.2776... \n", - "27 [[-0.1863702, 0.36686182, 0.22280839, -0.21697... \n", - "28 [[-0.3548704, 0.1917099, 0.28657728, -0.262703... \n", - "29 [[-0.28405702, 0.10858213, 0.32111079, -0.2300... \n", - "30 [[-0.47336444, 0.08036472, 0.37820706, -0.2123... \n", - "31 [[-0.3776276, 0.21458092, 0.3001521, -0.152129... \n", - "32 [[-0.2948512, 0.27886307, 0.23734306, -0.22463... \n", - "33 [[-0.32530716, 0.24720953, 0.26123106, -0.2493... \n", - "34 [[-0.37683305, 0.3004347, 0.30100918, -0.21106... \n", - "35 [[-0.30782086, 0.2336929, 0.23015884, -0.16083... \n", - "36 [[-0.3048136, 0.16629891, 0.3336691, -0.178628... \n", - "37 [[-0.4397936, 0.15727538, 0.35291147, -0.22082... \n", - "38 [[-0.4935615, 0.10821018, 0.1830138, -0.252587... \n", - "39 [[-0.2861055, 0.08323312, 0.34479225, -0.18034... \n", - "40 [[-0.37095174, 0.32116163, 0.20662963, -0.2790... \n", - "41 [[-0.15027289, 0.31890064, 0.17519885, -0.2029... \n", - "42 [[-0.3795819, 0.24610856, 0.26605865, -0.28016... \n", - "43 [[-0.46518034, 0.22024783, 0.28029412, -0.2428... \n", + " background \\\n", + "0 Interleukin 6 (IL-6) is a cytokine with signif... \n", + "1 The provided documents do not offer explicit i... \n", + "2 Based on the provided context and general know... \n", + "3 C-reactive protein (CRP) is an acute-phase pro... \n", + "4 The context provided from the document does no... \n", + "5 Based on the provided context, there is no spe... \n", + "6 Based on the provided context and familiar pri... \n", + "7 The document context provided does not explici... \n", + "8 The specific species 'Ab_sR_IL6{serum}' does n... \n", + "9 Based on the provided context, there is limite... \n", + "10 C-reactive protein (CRP) is an important bioma... \n", + "11 Based on the provided context and general know... \n", + "12 The species referred to as 'R_IL6_gp130{liver}... \n", + "13 The species referred to as 'sR_IL6{liver}' in ... \n", + "14 The context provided does not include specific... \n", + "15 The provided context discusses the role of IL-... \n", + "16 The provided documents mention several compone... \n", + "17 The context provided does not contain specific... \n", + "18 Based on the provided context, the specific in... \n", + "19 The context provided does not contain specific... \n", + "20 Based on the given context, there is no specif... \n", + "21 The provided context does not contain specific... \n", + "22 C-reactive protein (CRP) is an acute-phase pro... \n", + "23 The provided context does not specifically men... \n", + "24 The species 'sR_IL6_sgp130{liver}' likely repr... \n", + "25 The provided context does not specifically men... \n", + "26 Based on the provided context, there appears t... \n", + "27 The context provided does not offer specific i... \n", + "28 Based on the provided context and general scie... \n", + "29 The species referred to as 'sR_IL6{gut}' likel... \n", + "30 The context provided does not explicitly menti... \n", + "31 The context provided does not directly mention... \n", + "32 Based on the provided context, there is no spe... \n", + "33 The context provided does not include specific... \n", + "34 The provided context does not contain direct i... \n", + "35 Based on the context provided, there appears t... \n", + "36 The context provided does not contain specific... \n", + "37 Based on the context provided, IL6{gut} likely... \n", + "38 The species 'sgp130{gut}', likely derived from... \n", + "39 Based on the provided context and general know... \n", + "40 Based on the context provided and general know... \n", + "41 The context provided does not contain specific... \n", + "42 The context does not provide explicit informat... \n", + "43 The context provided does not explicitly menti... \n", "\n", - " best_node best_code \n", - "0 CLEC7A (Dectin-1) signaling_(62768) R-HSA-5607764 \n", - "1 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "2 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "3 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", - "4 G alpha (12/13) signalling events_(128349) R-HSA-416482 \n", - "5 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "6 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "7 Cytoprotection by HMOX1_(63064) R-HSA-9707564 \n", - "8 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "9 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", - "10 Tezacaftor_(15045) DB11712 \n", - "11 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "12 CLEC7A (Dectin-1) signaling_(62768) R-HSA-5607764 \n", - "13 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "14 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "15 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "16 CLEC7A (Dectin-1) signaling_(62768) R-HSA-5607764 \n", - "17 The NLRP3 inflammasome_(128804) R-HSA-844456 \n", - "18 MyD88:MAL(TIRAP) cascade initiated on plasma m... R-HSA-166058 \n", - "19 NOD1/2 Signaling Pathway_(127908) R-HSA-168638 \n", - "20 Regulation of Complement cascade_(127866) R-HSA-977606 \n", - "21 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", - "22 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", - "23 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "24 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "25 CLEC7A (Dectin-1) signaling_(62768) R-HSA-5607764 \n", - "26 Cytoprotection by HMOX1_(63064) R-HSA-9707564 \n", - "27 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", - "28 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "29 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "30 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "31 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "32 Regulation of TLR by endogenous ligand_(127918) R-HSA-5686938 \n", - "33 Growth hormone receptor signaling_(127694) R-HSA-982772 \n", - "34 Signaling by MST1_(129128) R-HSA-8852405 \n", - "35 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", - "36 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "37 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "38 Cytoprotection by HMOX1_(63064) R-HSA-9707564 \n", - "39 Interleukin-6 signaling_(128814) R-HSA-1059683 \n", - "40 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "41 Immunoregulatory interactions between a Lympho... R-HSA-198933 \n", - "42 Interleukin-2 signaling_(128499) R-HSA-9020558 \n", - "43 Interleukin-2 signaling_(128499) R-HSA-9020558 " + " BERT_embedding best_node best_code \n", + "0 [[-0.36046556, 0.1984801, 0.34831223, -0.13759... CXCL8_(2978) 3576 \n", + "1 [[-0.33606362, 0.14078653, 0.28409472, -0.1816... IL2RA_(7059) 3559 \n", + "2 [[-0.35146952, 0.10439779, 0.35805824, -0.1242... IL1B_(1004) 3553 \n", + "3 [[-0.51451033, 0.34030703, 0.27825356, -0.1979... CXCL8_(2978) 3576 \n", + "4 [[-0.19817938, 0.3326699, 0.28404108, -0.11455... CRP_(2384) 1401 \n", + "5 [[-0.38143575, 0.16730621, 0.33593783, -0.1761... IL2RA_(7059) 3559 \n", + "6 [[-0.26659864, 0.37297052, 0.12752607, -0.0740... CRP_(2384) 1401 \n", + "7 [[-0.25748405, 0.3326551, 0.22365786, -0.12952... CRP_(2384) 1401 \n", + "8 [[-0.37747848, 0.26106745, 0.29221672, -0.1456... IL2RA_(7059) 3559 \n", + "9 [[-0.4193665, 0.19158283, 0.2804547, -0.165872... IL2RA_(7059) 3559 \n", + "10 [[-0.39912638, 0.23087408, 0.27915168, -0.1415... CRP_(2384) 1401 \n", + "11 [[-0.33445, 0.23918422, 0.2927546, -0.17028718... IL1B_(1004) 3553 \n", + "12 [[-0.40478626, 0.17814767, 0.27589074, -0.1340... IL1B_(1004) 3553 \n", + "13 [[-0.45756304, 0.17891681, 0.36423725, -0.2334... IL1B_(1004) 3553 \n", + "14 [[-0.4199063, 0.25244138, 0.23973583, -0.12047... IL1B_(1004) 3553 \n", + "15 [[-0.5299805, 0.20470381, 0.21622677, -0.16921... IL1B_(1004) 3553 \n", + "16 [[-0.40827248, 0.1906287, 0.36825097, -0.23810... IL1B_(1004) 3553 \n", + "17 [[-0.29601544, 0.32257238, 0.11635402, -0.1388... MMP9_(3474) 4318 \n", + "18 [[-0.48407704, 0.26490304, 0.2329331, -0.23542... IL1B_(1004) 3553 \n", + "19 [[-0.31865203, 0.20982854, 0.33414608, -0.1467... IL1B_(1004) 3553 \n", + "20 [[-0.28650454, 0.28451994, 0.22697207, -0.1883... IL1B_(1004) 3553 \n", + "21 [[-0.3657858, 0.18391879, 0.26731104, -0.14256... IL1B_(1004) 3553 \n", + "22 [[-0.52379715, 0.26640716, 0.24741346, -0.2049... IL1B_(1004) 3553 \n", + "23 [[-0.41315806, 0.19693111, 0.18671003, -0.1230... IL1B_(1004) 3553 \n", + "24 [[-0.43109208, 0.25532103, 0.27182448, -0.1714... IL1B_(1004) 3553 \n", + "25 [[-0.31681302, 0.38205892, 0.13448949, -0.1530... CRP_(2384) 1401 \n", + "26 [[-0.25571656, 0.41298026, 0.169575, -0.146192... CRP_(2384) 1401 \n", + "27 [[-0.2570913, 0.29179507, 0.19184656, -0.14854... CRP_(2384) 1401 \n", + "28 [[-0.3885418, 0.18170443, 0.34147617, -0.20549... IL1B_(1004) 3553 \n", + "29 [[-0.4339128, 0.22657649, 0.25634766, -0.19923... IL1B_(1004) 3553 \n", + "30 [[-0.39961886, 0.21250604, 0.20553315, -0.1531... IL1B_(1004) 3553 \n", + "31 [[-0.4055007, 0.20729655, 0.2815721, -0.172021... IL1B_(1004) 3553 \n", + "32 [[-0.19464502, 0.30159003, 0.034058932, -0.134... IL1B_(1004) 3553 \n", + "33 [[-0.3604745, 0.23800118, 0.19214159, -0.21026... IL1B_(1004) 3553 \n", + "34 [[-0.41001073, 0.18395737, 0.21566965, -0.1557... IL1B_(1004) 3553 \n", + "35 [[-0.1892068, 0.32208663, 0.13539186, -0.07255... MMP9_(3474) 4318 \n", + "36 [[-0.366351, 0.21531877, 0.2917647, -0.1173586... CRP_(2384) 1401 \n", + "37 [[-0.38345662, 0.14892936, 0.283594, -0.155339... IL1B_(1004) 3553 \n", + "38 [[-0.44768405, 0.19976878, 0.17069031, -0.1916... IL1B_(1004) 3553 \n", + "39 [[-0.45934308, 0.19494462, 0.22395587, -0.1774... IL1B_(1004) 3553 \n", + "40 [[-0.3002606, 0.34374207, 0.15582994, -0.14586... CXCL8_(2978) 3576 \n", + "41 [[-0.3193748, 0.24593732, 0.22288847, -0.09116... IL1B_(1004) 3553 \n", + "42 [[-0.44073004, 0.20752984, 0.22041091, -0.1554... IL1B_(1004) 3553 \n", + "43 [[-0.15118778, 0.33757055, 0.18688324, -0.0879... CRP_(2384) 1401 " ] }, - "execution_count": 22, + "execution_count": 18, "metadata": {}, "output_type": "execute_result" } @@ -9037,15 +1866,7 @@ { "cell_type": "code", "execution_count": null, - "id": "70697134-924f-4594-9dd1-c6e52bc166c0", - "metadata": {}, - "outputs": [], - "source": [] - }, - { - "cell_type": "code", - "execution_count": null, - "id": "e1ae5b43-e036-48a9-8c4b-924e5fcbc87d", + "id": "535fa61e-2d7a-4c44-9e92-f8124ac60b27", "metadata": {}, "outputs": [], "source": [] diff --git a/notebook/model537_mapping.csv b/notebook/model537_mapping.csv new file mode 100644 index 00000000..1a9bba50 --- /dev/null +++ b/notebook/model537_mapping.csv @@ -0,0 +1,45 @@ +Species Name ,Original Identifiers,Annotated Identifiers +Ab_R,"P08887, FMA:62871","Gene ID: 3570, SNOMEDCT:112133008" +Ab_sR_IL6{gut},"P08887, P05231, FMA:62871, PATO:0001537","Gene ID: 3570, Gene ID: 3569, BTO:0000545, SNOMEDCT:112133008" +Ab_sR_IL6{liver},"P08887, P05231, FMA:62871, PATO:0001537","Gene ID: 3570, Gene ID: 3569, BTO:0000759, SNOMEDCT:112133008" +Ab_sR_IL6{serum},"P08887, P05231, FMA:62871, PATO:0001537","Gene ID: 3570, Gene ID: 3569, BTO:0001239, SNOMEDCT:112133008" +Ab_sR{gut},"P08887, FMA:62871, PATO:0001537","Gene ID: 3570, BTO:0000545, SNOMEDCT:112133008" +Ab_sR{liver},"P08887, FMA:62871, PATO:0001537","Gene ID: 3570, BTO:0000759, SNOMEDCT:112133008" +Ab_sR{serum},"P08887, FMA:62871, PATO:0001537","Gene ID: 3570, BTO:0001239, SNOMEDCT:112133008" +Ab{gut},FMA:62871,"BTO:0000545, SNOMEDCT:112133008" +Ab{liver},FMA:62871,"BTO:0000759, SNOMEDCT:112133008" +Ab{peripheral},FMA:62871,"PATO:0002107, SNOMEDCT:112133008" +Ab{serum},"FMA:62871, CHEBI:52217","BTO:0001239, SNOMEDCT:112133008" +CRP (% of baseline),P02741,Gene ID: 1401 +CRP Suppression (%),P02741,"Gene ID: 1401, SNOMEDCT:8063300" +CRPExtracellular,P02741,"Gene ID: 1401, SNOMEDCT:69320009" +CRP{liver},P02741,"Gene ID: 1401, BTO:0000759" +CRP{serum},P02741,"Gene ID: 1401, BTO:0001239" +geneProduct,CCO:U0000003,FMA:293363 +gp130{gut},PR:000001868,"Gene ID: 3572, BTO:0000545" +gp130{liver},PR:000001868,"Gene ID: 3572, BTO:0000759" +IL6{gut},P05231,"Gene ID: 3569, BTO:0000545" +IL6{liver},P05231,"Gene ID: 3569, BTO:0000759" +IL6{serum},P05231,"Gene ID: 3569, BTO:0001239" +pSTAT3{gut},"PR:000002089, SBO:0000216","Gene ID: 6774, BTO:0000545, PATO:0002262" +pSTAT3{liver},"PR:000002089, SBO:0000216","Gene ID: 6774, BTO:0000759, PATO:0002262" +R,P08887,Gene ID: 3570 +R_IL6,"P08887, P05231","Gene ID: 3570, Gene ID: 3569" +R_IL6_gp130{gut},"P08887, P05231, PR:000001868","Gene ID: 3570, Gene ID: 3569, Gene ID: 3572, BTO:0000545" +R_IL6_gp130{liver},"P08887, P05231, PR:000001868","Gene ID: 3570, Gene ID: 3569, Gene ID: 3572, BTO:0000759" +Reactive{gut},"P08887, P05231, PR:000001868, SBO:0000286, PATO:0002354","Gene ID: 3570, Gene ID: 3569, Gene ID: 3572, BTO:0000545" +Reactive{liver},"P08887, P05231, PR:000001868, SBO:0000286, PATO:0002354","Gene ID: 3570, Gene ID: 3569, Gene ID: 3572, BTO:0000759" +sgp130{gut},"PR:000001868, PATO:0001537"," Gene ID: 3572, BTO:0000545" +sgp130{liver},"PR:000001868, PATO:0001537"," Gene ID: 3572, BTO:0000759" +sgp130{serum},"PR:000001868, PATO:0001537"," Gene ID: 3572, BTO:0001239" +sR_IL6_sgp130{gut},"P08887, P05231, PR:000001868, PATO:0001537","Gene ID: 3570, Gene ID: 3569, Gene ID: 3572, BTO:0000545" +sR_IL6_sgp130{liver},"P08887, P05231, PR:000001868, PATO:0001537","Gene ID: 3570, Gene ID: 3569, Gene ID: 3572, BTO:0000759" +sR_IL6_sgp130{serum},"P08887, P05231, PR:000001868, PATO:0001537","Gene ID: 3570, Gene ID: 3569, Gene ID: 3572, BTO:0001239" +sR_IL6{gut},"P08887, P05231, PATO:0001537","Gene ID: 3570, Gene ID: 3569, BTO:0000545" +sR_IL6{liver},"P08887, P05231, PATO:0001537","Gene ID: 3570, Gene ID: 3569, BTO:0000759" +sR_IL6{serum},"P08887, P05231, PATO:0001537","Gene ID: 3570, Gene ID: 3569, BTO:0001239" +sR{gut},"P08887, PATO:0001537","Gene ID: 3570, BTO:0000545" +sR{liver},"P08887, PATO:0001537","Gene ID: 3570, BTO:0000759" +sR{serum},"P08887, PATO:0001537","Gene ID: 3570, BTO:0001239" +STAT3{gut},PR:000002089,"Gene ID: 6774, BTO:0000545" +STAT3{liver},PR:000002089,"Gene ID: 6774, BTO:0000759" diff --git a/notebook/sbml_rag_notebook.ipynb b/notebook/sbml_rag_notebook.ipynb index 75fd808d..722db6ef 100644 --- a/notebook/sbml_rag_notebook.ipynb +++ b/notebook/sbml_rag_notebook.ipynb @@ -2008,9 +2008,9 @@ ], "metadata": { "kernelspec": { - "display_name": "Python 3", + "display_name": "Python (myenv)", "language": "python", - "name": "python3" + "name": "myenv" }, "language_info": { "codemirror_mode": { diff --git a/notebook/species_backgrounds.csv b/notebook/species_backgrounds.csv deleted file mode 100644 index 39c3cd8c..00000000 --- a/notebook/species_backgrounds.csv +++ /dev/null @@ -1,653 +0,0 @@ -id,name,original_name,compartment,background -mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6,IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context, IL6 (Interleukin 6) is a cytokine that plays a crucial role in immune regulation, particularly in the context of inflammatory conditions such as Crohn's disease and rheumatoid arthritis. - -### Biological Function: -IL6 is involved in immune responses and inflammation. It contributes significantly to the survival of T-cells and confers resistance to apoptosis in the lamina propria, a layer of the intestinal mucosa, thereby playing an important role in the pathology of inflammatory bowel diseases like Crohn's disease. It is also associated with elevated chemokine secretion. - -### Role in Pathways: -IL6 signaling can occur through two main pathways: -1. **Classical Pathway**: This involves the membrane-bound IL-6 receptor (IL-6Rα). In this process, IL6 binds to IL-6Rα on the cell membrane, forming a complex that recruits the membrane-bound coreceptor gp130, which forms a heterotrimeric complex. This complex dimerizes into a hexameric receptor complex, activating downstream signaling cascades. -2. **Trans-signaling Pathway**: Here, IL6 binds to a soluble form of IL-6Rα (sIL-6Rα), and this complex also recruits gp130, following a similar mechanism to form an active signaling complex. Trans-signaling is particularly important in pathological conditions where traditional signaling pathways are altered or less efficient. - -### Interactions with Other Molecules: -IL6 interacts with both membrane-bound and soluble forms of its receptor IL-6Rα to initiate signaling cascades. The activated receptor complex initiates phosphorylation of Janus kinase (Jak) family proteins, which subsequently phosphorylate signal transducer and activator of transcription 3 (STAT3). This signaling cascade is pivotal in mediating the biological effects of IL6 in inflammatory and immune responses. Additionally, the model demonstrates interactions between IL6, its receptors, and therapeutic antibodies like tocilizumab, which are designed to suppress IL6 signaling. - -### Importance in the Biological System Being Modeled: -In the context of Crohn's disease, IL6 is highlighted as a significant mediator of immune regulation, particularly due to its role in enhancing T-cell survival and modulating chemokine secretion, which are key components of the disease's pathology. Targeting IL6 signaling pathways, whether through classical or trans-signaling, could be a therapeutic strategy for managing inflammatory responses associated with Crohn’s disease and similar conditions. - -In summary, IL6 is a critical cytokine involved in immune regulation and inflammatory signaling, serving as both a potential target for therapeutic intervention and a key player in the pathogenesis of diseases such as Crohn's disease and rheumatoid arthritis." -mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130,sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species 'sgp130' appears to be related to a modified version of the gp130 protein, specifically referred to as sgp130Fc. Here is a summary based on the provided context: - -1. **Biological Function**: sgp130 is primarily involved in inhibiting IL-6 trans-signaling. This is achieved by its ability to bind to the IL-6/sIL-6Rα complex. The fusion protein sgp130Fc, which combines the extracellular portion of gp130 with the Fc region of human IgG1, has been shown to inhibit this pathway in cultured cells. - -2. **Role in Pathways**: The primary pathway of interest involving sgp130 is the IL-6 signaling pathway. IL-6 is a cytokine implicated in various inflammatory processes, and its trans-signaling via the soluble IL-6 receptor (sIL-6Rα) is distinct from classical signaling. The role of sgp130 is to regulate this trans-signaling pathway by competing with cell surface gp130 receptors, thereby reducing the pro-inflammatory effects mediated by IL-6/sIL-6Rα. - -3. **Interactions with Other Molecules**: sgp130 interacts with the IL-6/sIL-6Rα complex. In the presence of high amounts of sgp130, most of the IL-6 is bound, thus preventing it from mediating its effects via the trans-signaling pathway. - -4. **Importance in the Biological System**: Despite its potential therapeutic role, the sensitivity analysis from the provided context suggests that sgp130 has a relatively low impact on the steady-state dynamics of the system being modeled. This is attributed to its high baseline concentration compared to IL-6, implying that large changes in sgp130 levels are needed to achieve significant biological effects. Therefore, the efficacy of sgp130-based therapies, like sgp130Fc, may be limited and require high doses to be effective. - -Overall, sgp130 serves as a regulatory molecule within the IL-6 signaling pathway, specifically targeting and mitigating the effects of IL-6 trans-signaling, though its standalone therapeutic potential may be limited due to high baseline levels and lower impact on system sensitivity." -mw810ff751_fa4e_4143_bd50_169b3e325e1e,sR_IL6_sgp130,sR_IL6_sgp130,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species 'sR_IL6_sgp130' appears to be involved in the system of IL-6 signaling, which plays a critical role in inflammatory responses such as those found in diseases like Crohn's disease. Based on the provided context, here's a summary of its background information: - -1. **Biological Function**: sR_IL6_sgp130 is likely related to the IL-6 signaling pathway. It is suggested to be a complex involving soluble IL-6 receptor (sIL-6R) and sgp130, which is a fusion protein comprised of the extracellular portion of the gp130 receptor and the Fc region of human IgG1. The gp130 receptor is part of the signaling pathway for IL-6, a cytokine involved in immune responses. - -2. **Role in Pathways**: sR_IL6_sgp130 is involved in the inhibition of IL-6 trans-signaling. This pathway is crucial for mediating pro-inflammatory responses. The context suggests that sgp130 can bind to the IL-6/sIL-6Rα complex, potentially blocking further signaling within this pathway. - -3. **Interactions with Other Molecules**: The species interacts with IL-6 and sIL-6Rα. The fusion protein sgp130Fc has been shown to bind to the IL-6/sIL-6Rα complex, suggesting that sR_IL6_sgp130 may act to sequester this complex and prevent it from engaging with cell surface receptors, thereby inhibiting downstream signaling, including pSTAT3 activation. - -4. **Importance in the Biological System Being Modeled**: Despite its role in inhibiting IL-6 signaling, sensitivity analyses indicate that altering sgp130 levels has a minimal effect on the steady-state dynamics of the system due to its high baseline concentration. This suggests that while sR_IL6_sgp130 has the potential to influence inflammation pathways, its impact may be limited under normal conditions and would require significant changes to yield observable effects. - -Overall, sR_IL6_sgp130 represents an important therapeutic target or molecule within the context of IL-6 mediated diseases, but its natural abundance and resultant low system sensitivity under basal conditions make it a challenging target for effective therapeutic intervention without substantial dosage alterations." -mw114aa90f_5f5b_4fe8_9406_361c8489b6a1,CRP,CRP,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"C-reactive protein (CRP) is a crucial protein in the context of inflammation and immune response regulation. Based on the provided context and general knowledge about CRP, the following summarizes its biological role and significance: - -1. **Biological Function**: - - CRP is an acute-phase protein, primarily produced in the liver in response to inflammation. It is commonly used as a marker to assess inflammatory states in various conditions. The production is typically induced by cytokines such as interleukin-6 (IL-6). - -2. **Role in Pathways**: - - CRP plays a part in the systemic response to inflammation, often used clinically as an indicator for inflammatory conditions such as infections and autoimmune diseases. In the context described, CRP levels are used to monitor and model the effect of treatments targeting components of the IL-6 signaling pathway, especially in diseases like Crohn's disease. - -3. **Interactions with Other Molecules**: - - CRP interacts with various components of the immune system. It can bind to phosphocholine on the surface of dead or dying cells (and some types of bacteria) to activate the complement system, promoting phagocytosis by macrophages, which is a crucial aspect of its role in inflammation. - - In the context of the presented data, CRP levels are modulated through pathways involving IL-6 and its receptor (IL-6Rα), showcasing its interconnected role in immune signaling pathways. - -4. **Importance in the Biological System Being Modeled**: - - Within the model described, CRP serves as a key biomarker for the effectiveness of treatment strategies targeting IL-6 signaling. The modulation of CRP levels indicates the level of inflammation and the success of therapeutic interventions aimed at reducing inflammation by inhibiting IL-6 activity. - - The document suggests the use of CRP levels to validate and predict the outcomes of therapeutic interventions, underlining its importance as a measurable outcome in clinical and modeling studies. - -Overall, CRP acts as an essential biomarker and participant in inflammatory pathways, and its levels are indicative of the inflammatory state and the impact of medical treatments in the studied model." -mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc,sR,sR,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context, there is limited direct information regarding the species 'sR' with ID mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc. However, we can infer some details based on the context of similar biological components mentioned. - -1. **Biological Function**: The context does not specify a unique biological function for 'sR'. However, it mentions interactions involving IL-6 and sIL-6R, suggesting that 'sR' might be associated with receptor or signaling functions in the IL-6 pathway. sIL-6R usually stands for soluble IL-6 receptor, which is involved in extending the effects of the IL-6 cytokine beyond cells that have membrane-bound receptors. - -2. **Role in Pathways**: Similar to sIL-6R and other molecules like sgp130, 'sR' might play a role in the modulation of signaling pathways. IL-6 signaling pathways involve activation and modulation through receptors, influencing gene transcription and protein production. It's plausible that 'sR' participates in similar pathways, potentially affecting signal transduction and biological responses. - -3. **Interactions with Other Molecules**: Although not directly mentioned, 'sR' perhaps interacts with other components in the IL-6 signaling cascade such as IL-6, its receptors (like IL-6R), and possibly soluble receptors like sgp130. Intermediates such as Jak and STAT3 are common in such pathways, and 'sR' might influence or be influenced by these interactions. - -4. **Importance in the Biological System**: The significance of 'sR' is not explicitly described, but it could be an important regulator within the system. Given the extensive discussion on IL-6 and its modulation by soluble receptors and sgp130, 'sR' might contribute to these dynamics, affecting cellular responses to IL-6 signaling and influencing conditions like inflammatory responses or chronic disease states. - -In summary, while not directly detailed, 'sR' may operate similarly to other receptors or molecules in the IL-6 signaling context, playing a part in modulation, interaction, and systemic effects within biological pathways." -mw03db56ac_8dc6_4931_ae82_fef706d2ee3d,sR_IL6,sR_IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"The species ""sR_IL6,"" identified by the ID mw03db56ac_8dc6_4931_ae82_fef706d2ee3d, is likely related to the soluble interleukin-6 receptor (sIL-6R) based on the context provided. Here is an interpretation and breakdown of its role and function: - -1. **Biological Function**: - - sR_IL6 is likely analogous to sIL-6R, which functions as a part of the IL-6 signaling pathway. The soluble receptor binds to interleukin-6 (IL-6), facilitating its interaction with gp130, an essential component for signal transduction. - -2. **Role in Pathways**: - - IL-6 can signal through classical and trans-signaling pathways. In the classical pathway, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), while in the trans-signaling pathway, the soluble receptor (sIL-6R) binds IL-6, allowing the complex to interact with gp130 on cells that do not express IL-6R. This interaction is crucial for activating downstream signaling pathways, such as the JAK/STAT pathway, specifically promoting STAT3 phosphorylation (pSTAT3), which can lead to gene transcription including the acute phase protein C-reactive protein (CRP). - -3. **Interactions with Other Molecules**: - - sR_IL6 (sIL-6R) interacts directly with IL-6 to form the IL-6/sIL-6R complex. This complex can be sequestered by the soluble gp130 (sgp130), inhibiting the signaling and potentially modulating the intensity or range of the IL-6 mediated response. - -4. **Importance in the Biological System**: - - The IL-6/sIL-6R complex plays a role in immune regulation, as indicated by its involvement in models studying conditions like Crohn’s disease. It has significance in how inflammation is managed within the body, especially in the context of inflammatory diseases. - - The model indicates the regulation of sR_IL6 levels may impact therapeutic strategies, with alterations in dosages of anti-IL-6 antibodies showing variable efficacy. - -Overall, the sR_IL6 is a critical component in mediating IL-6 trans-signaling, thus having a significant impact on immune regulation and potential therapeutic strategies for inflammatory diseases." -mwf345ed7a_0622_403c_b816_c8749a2c9ded,Ab,Ab,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context from the documents, the species named 'Ab' (ID: mwf345ed7a_0622_403c_b816_c8749a2c9ded, located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e) is likely referring to an antibody, given the context in which it's mentioned, particularly in relation to drug doses and targeting of specific molecular complexes. - -Here are the inferred details about 'Ab' based on the context: - -- **Biological Function**: The antibody ('Ab') likely functions in binding to specific target molecules, probably related to the immune system or inflammation pathways, as inferred from the association with IL-6/sIL-6Rα complexes—the interleukin-6 receptor alpha complex. - -- **Role in Pathways**: 'Ab' seems to play a role in modulating pathways related to inflammatory responses, especially through interactions with the IL-6 signaling pathway. It appears to be part of a therapeutic strategy, potentially targeting cytokines such as IL-6 and its soluble receptor complex to regulate inflammation, as noted by the mention of CRP suppression (C-reactive protein—a marker for inflammation). - -- **Interactions with Other Molecules**: The context suggests a role in interacting with IL-6 and sIL-6Rα complexes. The antibody serves as a limiting factor in neutralizing or modulating these complexes within the biological system, influencing serum biomarker levels like CRP. - -- **Importance in the Biological System Being Modeled**: 'Ab' is significant in the modeled system as a therapeutic agent, potentially used in treating inflammatory conditions by targeting cytokine pathways. By affecting IL-6-related pathways, it appears to reduce inflammatory responses, as evidenced by experiments and modeling of serum CRP suppression following treatments. - -Though specific details about 'Ab' are not explicitly provided in the excerpts, it can be inferred that 'Ab' is a therapeutic antibody with a function in targeting pro-inflammatory cytokine pathways within the given biological context, aiming to control or reduce inflammatory processes." -mw1da111f2_a036_4392_8512_015005bdcbb7,Ab_sR,Ab_sR,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the provided context, specific information about the species ""Ab_sR"" (ID: mw1da111f2_a036_4392_8512_015005bdcbb7, located in mw53ffe9e6_beef_45c4_90a5_a79197ed506e) is not directly mentioned. However, we can infer its potential role and importance in the biological system being modeled by examining the surrounding biological components and pathways mentioned in the context. - -### Inferred Background Information about Ab_sR - -1. **Biological Function:** - - The context suggests a focus on interleukin-6 (IL-6) and its receptor interactions, particularly involving the soluble IL-6 receptor (sIL-6R) and its complexes. Given the naming convention ""Ab_sR,"" it is reasonable to infer that Ab_sR could represent an antibody (Ab) specific to a soluble receptor (sR), likely related to the IL-6 signaling pathway. - -2. **Role in Pathways:** - - The IL-6 signaling pathway involves several key interactions, including the formation of complexes with sIL-6R, which are critical for signal transduction. Ab_sR might participate in modulating or inhibiting this pathway, possibly by binding to the sIL-6R or other pathway components, potentially altering the pathway's output like the downstream effects on C-reactive protein (CRP) production. - -3. **Interactions with Other Molecules:** - - Within the pathway context, Ab_sR may interact with IL-6, sIL-6R, and possibly other related components like the glycoprotein (gp130), which are crucial for IL-6 signal transduction. Its role might be to bind these molecules to modulate their activity or bioavailability in the system, akin to the action of therapeutic antibodies that target cytokine receptors. - -4. **Importance in the Biological System:** - - Ab_sR could be significant for fine-tuning the inflammatory response mediated by IL-6 signaling. By regulating or inhibiting the function of the IL-6/sIL-6R pathway, Ab_sR might contribute to controlling inflammation and related processes in tissues such as the liver and gastrointestinal tract. This modulation could be especially important in conditions where IL-6 plays a pivotal role, such as in autoimmune diseases or chronic inflammatory states. - -Overall, while direct information on Ab_sR is not available, the context allows us to hypothesize its role as a regulatory or inhibitory agent within the IL-6 signaling pathway, potentially serving as a therapeutic molecule targeting inflammation-related pathways." -mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac,Ab_sR_IL6,Ab_sR_IL6,mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the context provided, there is no specific mention of the species 'Ab_sR_IL6' by name. However, the context revolves around interactions involving IL-6, its receptor sIL-6Rα, and antibodies targeting these molecules. We can infer certain characteristics and roles this species might fulfill based on the general knowledge of similar biological components and the information presented: - -1. **Biological Function**: Proteins associated with the suffix 'Ab' usually refer to antibodies. Given the context, 'Ab_sR_IL6' likely functions as an antibody targeting the IL-6 receptor, specifically the soluble form sIL-6Rα. Antibodies like these are typically designed to bind to their target receptor, potentially blocking its interaction with its ligand (IL-6) or other molecules, resulting in modulation of a biological pathway. - -2. **Role in Pathways**: In the immune regulation context, this antibody likely plays a role in modulating IL-6-mediated signaling pathways. The data discusses targeting the IL-6/sIL-6Rα complex to modulate responses in the immune system, particularly in inflammatory conditions like Crohn’s Disease and rheumatoid arthritis. By interfering with this pathway, the antibody likely serves to suppress the pro-inflammatory effects mediated by IL-6. - -3. **Interactions with Other Molecules**: The document specifically talks about the interaction of antibodies with sIL-6Rα and IL-6, suggesting that 'Ab_sR_IL6' could interact with these components. The interaction with sIL-6Rα likely prevents the receptor from associating with IL-6 or gp130 (another crucial signaling component). This interference can result in reduced signaling through the JAK-STAT pathway, which is implicated in inflammation and autoimmune disease processes. - -4. **Importance in the Biological System**: The importance of such an antibody in the model is likely related to its ability to control inflammatory processes. By targeting sIL-6Rα, it could help reduce the production of inflammatory mediators like C-reactive protein (CRP) and other gene products important in the inflammatory response. In the context of diseases like Crohn’s Disease, the use of such an antibody could be significant for reducing symptoms and controlling disease progression. - -Given these points, 'Ab_sR_IL6' likely represents a therapeutic antibody targeted towards IL-6 signaling components, playing a crucial role in modulating immune responses in inflammatory diseases." -CRP_Suppression___,CRP Suppression (%),CRP Suppression (%),mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"CRP Suppression (%) refers to the extent to which the levels of C-reactive protein (CRP) in the serum are reduced from baseline levels. CRP is a biomarker typically used to assess inflammation and is often elevated in response to inflammatory conditions such as infections, chronic diseases, or autoimmune disorders. - -### Biological Function: -- **C-reactive protein (CRP):** CRP is a protein produced by the liver in response to inflammation. It is part of the body's immune response and acts as an opsonin, marking pathogens for destruction by immune cells. - -### Role in Pathways: -- **Inflammatory Pathways:** The suppression of CRP levels is a marker of reduced inflammation. In the context of treatments targeting cytokines like interleukin-6 (IL-6), the decrease in CRP is an indicator of the efficacy of such anti-inflammatory treatments. - -### Molecular Interactions: -- **Interaction with Interleukin-6 (IL-6):** IL-6 is a cytokine that stimulates CRP production. Anti-IL-6 or anti-IL-6 receptor therapies aim to reduce CRP levels by blocking the action of IL-6, thereby diminishing its signal for CRP synthesis. - -### Importance in the Biological System Being Modeled: -- **Treatment Efficacy Marker:** CRP Suppression (%) is used as a biomarker to evaluate the effectiveness of treatments, such as anti-IL-6 antibodies or anti-IL-6R antibodies, in reducing inflammation. The suppression percentage directly correlates with the reduction in inflammatory activity within the body. -- **Dose-response Analysis:** The relationship between drug dosage and CRP Suppression (%) is crucial for determining optimal dosing regimens. Increased CRP suppression with higher doses of anti-inflammatory drugs typically indicates greater efficacy, though it may plateau or saturate at certain dose levels. - -In summary, CRP Suppression (%) serves as a critical indicator for assessing the impact of therapeutic strategies aimed at managing inflammatory responses by targeting specific immune signaling pathways in the body." -CRP____of_baseline,CRP (% of baseline),CRP (% of baseline),mw53ffe9e6_beef_45c4_90a5_a79197ed506e,"Based on the context provided and general knowledge about C-reactive protein (CRP), I can summarize the following background information: - -1. **Biological Function**: - - CRP, or C-reactive protein, is a substance produced by the liver in response to inflammation. It is a member of the class of acute-phase proteins, which increase in concentration in response to inflammation. CRP is commonly measured in clinical settings as a marker of inflammation. - -2. **Role in Pathways**: - - CRP is part of the body's immune response and plays a role in recognizing pathogens and damaged cells, thereby promoting their clearance through interaction with the complement system and other immune pathways. The context involving IL-6 and anti–IL-6Rα antibody treatment suggests an interest in inflammatory pathways where CRP is a downstream marker of cytokine (like IL-6) activity. - -3. **Interactions with Other Molecules**: - - CRP interacts with phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) to activate the complement system. It is known that CRP levels are regulated by cytokines, particularly interleukin-6 (IL-6), which is relevant in the context of anti-IL-6 therapy described in the document. - -4. **Importance in the Biological System Being Modeled**: - - The suppression and modulation of serum CRP levels are used as a measure to validate models simulating the effects of anti-IL-6Rα antibody therapy (such as with tocilizumab) in clinical settings. In this context, CRP (% of baseline) acts as a biomarker to assess the efficacy of treatment options targeting inflammatory pathways and the IL-6 signaling axis. It indicates the level of inflammation within patients undergoing such treatments. - -The reference to CRP (% of baseline) reflects normalized data used to compare changes in serum CRP levels over time, particularly in response to medical interventions, such as administration of anti-inflammatory drugs. This emphasizes its utility as a reliable marker for evaluating treatment responses in clinical trials and models related to inflammatory diseases." -mw80848184_e2dd_47ce_86d7_7a21479342bd,gp130,gp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, the biological species named 'gp130' appears to be a critical component in the interleukin-6 (IL-6) signaling pathway. Here's a summary of its role and importance: - -### Biological Function: -- **Gp130** serves as a signal-transducing coreceptor in the IL-6 signaling pathway. -- It acts as part of a complex with the IL-6 receptor (IL-6R) and is involved in mediating the downstream effects of IL-6. - -### Role in Pathways: -- **IL-6 Signaling**: Gp130 is a key component in the assembly of the IL-6/IL-6R/gp130 complex. This is crucial for the signaling cascade that drives various inflammatory and immune responses. -- **Inhibition of IL-6 Trans-Signaling**: The soluble form of gp130 (sgp130) can inhibit IL-6 trans-signaling by binding to the IL-6/sIL-6Rα complex, preventing its interaction with membrane-bound gp130 and subsequent signaling. - -### Interactions with Other Molecules: -- **IL-6 and IL-6R**: Gp130 interacts with IL-6 bound to its receptor IL-6R, forming a complex necessary for initiating signal transduction. -- **Soluble IL-6 Receptor (sIL-6R)**: It is noted that sgp130 is a natural inhibitor of the soluble IL-6 receptor, indicating a regulatory role in modulating the availability and activity of IL-6. - -### Importance in the Biological System: -- Gp130 is vital for the modulation of immune responses and inflammation through its role in IL-6 signaling. -- **Therapeutic Potential**: Its soluble form, sgp130, has been studied for therapeutic applications, including its potential use in diseases characterized by excessive IL-6 signaling, such as Crohn's disease. The context mentions simulations of sgp130Fc (a fusion protein of sgp130 with the Fc region of an antibody) for therapeutic dosing. -- **Baseline Levels**: The high baseline levels of sgp130 compared to IL-6 indicate its prominent regulatory role in the signaling environment. - -In summary, gp130 is a crucial component of the IL-6 signaling pathway with significant implications in inflammation and immune modulation. Its interactions and regulatory capabilities make it a target for therapeutic intervention, especially in inflammatory diseases." -mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a,R_IL6_gp130,R_IL6_gp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context and general knowledge about similar biological components, the species 'R_IL6_gp130' likely refers to a complex involving interleukin-6 (IL-6), its receptor (IL-6R), and the signaling component gp130. Here's a summary of what is generally known about the components involved: - -1. **Biological Function:** - - Interleukin-6 (IL-6) is a cytokine involved in immune responses, inflammation, and hematopoiesis. It mediates its effects through the IL-6 receptor (IL-6R) and the signal transducer gp130. - - gp130 is a transmembrane protein that, upon IL-6 binding to IL-6R, forms a complex through which signal transduction occurs, initiating intracellular signaling cascades primarily involving the JAK-STAT pathway. - -2. **Role in Pathways:** - - The IL-6/IL-6R/gp130 signaling complex plays a crucial role in the JAK-STAT signaling pathway. This pathway is pivotal in promoting gene expression associated with inflammatory responses. - - The pathway can occur through classical signaling, where IL-6 binds to its membrane-bound receptor IL-6R, or through trans-signaling, where IL-6 binds to a soluble form of IL-6R (sIL-6R), interacting with membrane-bound gp130 in cells that do not express IL-6R. - -3. **Interactions with Other Molecules:** - - IL-6 binding to IL-6R and subsequent interaction with gp130 triggers gp130 dimerization and activation of associated JAK kinases, leading to phosphorylation and activation of STAT3, a transcription factor. - - Soluble gp130 (sgp130) can inhibit IL-6-mediated trans-signaling by binding to the IL-6/sIL-6R complex, preventing it from interacting with membrane-bound gp130. This natural inhibitor is significant as it selectively inhibits the trans-signaling pathway. - -4. **Importance in the Biological System Being Modeled:** - - The IL-6/gp130 signaling axis is critical in inflammatory diseases, including Crohn's disease and other autoimmune conditions. The document highlights the therapeutic potential of modulating this pathway, particularly using sgp130Fc (a fusion protein analog of gp130) to inhibit IL-6 trans-signaling. - - Pharmacokinetic (PK) studies and simulations of sgp130Fc are mentioned, indicating its evaluation as a therapeutic intervention targeting this pathway, aiming to reduce inflammation markers like CRP (C-reactive protein) and pSTAT3 in the gut. - -In summary, 'R_IL6_gp130' likely represents a signaling complex crucial for mediating inflammatory responses in various biological settings, making it a significant therapeutic target, especially in inflammatory and autoimmune diseases." -mw4638f126_8cb8_4021_ab41_6ae195743ba0,"sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The molecule in question, sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2), can be inferred to relate closely to soluble IL-6 receptor components based on its name and ID positioning within a model of IL-6 signaling. Although there is no explicit information about this exact species in the provided context, some relevant points about similar molecules can be derived. - -### **Biological Function:** -- **sIL-6R (soluble IL-6 receptor)**: Typically, sIL-6R refers to a soluble form of the IL-6 receptor, which allows IL-6 to transduce signals through cells that do not express the membrane-bound IL-6 receptor. This process is part of what is known as IL-6 trans-signaling. In the context of the model being described, sR_IL6 may play a similar role. - -### **Role in Pathways:** -- **IL-6 Signaling**: It functions within the IL-6 signaling pathway, which can occur via classical signaling or trans-signaling. Classical signaling involves membrane-bound IL-6R and gp130, while trans-signaling involves sIL-6R. -- **Interaction with sgp130**: The sIL-6R/IL-6 complex can be sequestered by another molecule, sgp130, preventing further signaling. - -### **Interactions with Other Molecules:** -- **IL-6/sIL-6R Complex**: It forms a complex with IL-6, which can engage with gp130 on cell membranes, activating downstream signaling cascades. -- **CRP Influence**: The production of sIL-6R is influenced by CRP (C-reactive protein), which mediates its shedding. - -### **Importance in the Biological System Being Modeled:** -- **Crohn’s Disease**: The IL-6/sIL-6Rα complex plays a significant role in the context of Crohn’s disease, a chronic inflammatory condition. Therapeutic strategies targeting this complex have been simulated to evaluate their effects on disease dynamics. -- **Pharmacological Efficacy**: In therapeutic models, blocking the IL-6/sIL-6Rα complex alongside free IL-6 has been shown to improve pharmacological efficacy, implying its critical role in modulating immune responses. - -In summary, sR_IL6 is likely involved in facilitating trans-signaling in IL-6 pathways, interacting with other components like IL-6, gp130, and CRP, with implications for inflammatory diseases such as Crohn’s disease. These inferred roles suggest its significance in the physiological and pathological contexts of IL-6 mediated immune regulation." -mw10315fa3_6f13_4618_bda8_a8694bd3c374,R,R,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The provided context refers to interactions and functions related to the interleukin-6 receptor (IL-6R), yet there is no explicit mention of a species or molecule specifically called 'R'. However, we can infer that 'R' might refer to the interleukin-6 receptor (IL-6R) or components associated with it based on the context of the documents provided. Here's a summary of relevant information that could be applicable to 'R', especially if it is related to IL-6R: - -1. **Biological Function**: - - The IL-6 receptor (IL-6R) plays a critical role in the immune response. It is involved in the signaling pathway for interleukin-6 (IL-6), a cytokine that influences immune regulation, inflammation, and hematopoiesis. - -2. **Role in Pathways**: - - IL-6R is a part of the Classical and Trans signaling pathways. In the Classical pathway, it binds IL-6, leading to dimerization with gp130 and activation of the JAK/STAT signaling cascade, particularly resulting in the phosphorylation and activation of STAT3. This pathway has significant implications for transcriptional regulation of various genes. - - The IL-6 trans-signaling involves soluble IL-6R (sIL-6R) and affects cells that do not naturally express IL-6R on their surface, further enabling broader physiological effects. - -3. **Interactions with Other Molecules**: - - IL-6R interacts with IL-6 and gp130 in both the Classical and Trans signaling pathways. - - Antibodies targeting IL-6R, such as those mentioned in the context (e.g., anti–IL-6Rα antibodies), are used to modulate its function, particularly as therapeutic interventions to reduce inflammation or lower C-reactive protein (CRP) levels. - -4. **Importance in the Biological System**: - - In the context of disease and therapy, IL-6R is a target for modulating inflammatory responses, as its activation leads to increased levels of acute-phase proteins such as CRP, which are markers for inflammation. - - The modulation of IL-6R, such as through the use of antibodies, is significant in clinical settings for managing conditions characterized by excessive inflammation or immune activation. - -Based on the described interactions and importance, if 'R' refers to the IL-6 receptor or a similar component, it acts as a central mediator in inflammatory pathways and is a critical target for therapeutic interventions." -mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1,"IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided and general knowledge about IL-6, here is a summary of the information regarding IL-6, particularly in the context of immune regulation and diseases like Crohn's disease: - -1. **Biological Function**: IL-6 is a cytokine that plays a critical role in the immune system. It is involved in the regulation of immune responses, inflammation, and hematopoiesis. IL-6 is an important mediator in the body's response to infections and tissue injuries, helping to stimulate immune response. - -2. **Role in Pathways**: IL-6 signaling occurs via two main pathways: - - The classical pathway, mediated by the membrane-bound IL-6 receptor (IL-6Rα), which interacts with IL-6 to initiate signaling. - - The trans-signaling pathway, which involves the soluble IL-6 receptor (sIL-6Rα). In this pathway, the IL-6/sIL-6Rα complex can bind to the gp130 membrane-bound receptor to form an active signaling complex that initiates further downstream effects, such as the activation of Janus kinase (Jak) family proteins and signal transducer and activator of transcription 3 (STAT3) phosphorylation. - -3. **Interactions with Other Molecules**: IL-6 interacts with both its membrane-bound and soluble receptors (IL-6Rα and sIL-6Rα) to form complexes that recruit gp130, leading to signal transduction. The interaction with gp130 is crucial as it leads to the formation of an active hexameric receptor complex which drives further signaling processes. - -4. **Importance in Biological Systems**: IL-6 is particularly significant in the pathology of inflammatory diseases, such as Crohn's disease. It contributes to enhanced T-cell survival and apoptosis resistance, as well as elevated chemokine secretion in the intestinal mucosa and peripheral blood. This makes IL-6 signaling a critical target for therapeutic interventions in such conditions. - -In summary, IL-6 is a multifunctional cytokine with essential roles in immune regulation and inflammatory responses, especially relevant to conditions like Crohn’s disease. Its ability to signal through multiple pathways and interact with various molecular complexes underscores its importance in maintaining immune homeostasis and its potential as a therapeutic target." -mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83,R_IL6,R_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The provided context does not explicitly detail the species 'R_IL6' with the specified ID. However, based on the information present and general biological knowledge, 'R_IL6' could potentially represent a receptor or related component involved in the Interleukin-6 (IL-6) signaling pathway. - -### General Knowledge Inference for 'R_IL6': -1. **Biological Function**: - - IL-6 is a cytokine that plays a critical role in immune response, inflammation, and hematopoiesis. It typically signals through a receptor complex that may include the IL-6 receptor (IL-6R) and a signal transducer such as gp130. - - The designation 'R_IL6' suggests it may be an IL-6 receptor component, involved in binding IL-6 and initiating downstream signaling pathways. - -2. **Role in Pathways**: - - IL-6 signaling involves the activation of the Janus kinase (Jak) and Signal Transducer and Activator of Transcription 3 (STAT3) pathway. Binding of IL-6 to its receptor complex activates these pathways, leading to the transcription of genes involved in inflammatory and immune responses. - - The context also mentions ""Classical"" and ""Trans"" pathways, suggesting classical signaling involves membrane-bound IL-6R, while trans-signaling involves soluble IL-6R (sIL-6R). - -3. **Interactions with Other Molecules**: - - IL-6 interacts with both its membrane-bound and soluble forms of IL-6R, which facilitates different signaling outcomes. - - Interaction with sIL-6R allows IL-6 to signal in cells that do not express membrane-bound IL-6R by associating with the ubiquitously expressed signal transducer, gp130. - - The term 'R_IL6' within a complex might specifically denote its interaction with these molecules in such pathways. - -4. **Importance in the Biological System**: - - IL-6 signaling is crucial for immune regulation and has been implicated in several inflammatory diseases such as Crohn’s disease and rheumatoid arthritis. - - Modulating IL-6 activity, often through its receptor interactions, is a therapeutic target for reducing chronic inflammation and autoimmune diseases. - -Overall, while the specific role of 'R_IL6' is not detailed in the provided text, understanding its potential place within IL-6 signaling pathways offers insights into its biological significance and therapeutic relevance." -mw0eb6c959_d408_45a0_a450_928b8c5876bb,Ractive,Ractive,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The provided context does not contain specific information about the species named 'Ractive' (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb, located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e). The text focuses primarily on the IL-6 signaling pathway, its associated components, and the effects of targeting this pathway with therapeutic antibodies such as anti-IL-6 and anti-IL-6Rα, particularly in the context of autoimmune diseases like Crohn's Disease and rheumatoid arthritis. - -Since there is no direct mention of 'Ractive' in the context, we can infer its nature based on the general themes discussed: - -1. **Biological Function & Role in Pathways**: Given the context's focus on the IL-6 pathway, Ractive might be hypothesized as a molecule related to cytokine signaling, possibly a receptor, a part of a signaling cascade, or even an associated regulatory protein modulating immune responses. - -2. **Interactions with Other Molecules**: In a systems biology model of immune regulation, Ractive might interact with cytokines (like IL-6), receptors (such as IL-6Rα), or downstream signaling molecules (e.g., STAT proteins). Its interactions would be crucial for understanding the dynamics of the immune response. - -3. **Importance in the Biological System**: If Ractive is indeed involved in the IL-6 mediated pathway, it would be important for modulating immune responses, potentially influencing inflammation and immune system activity, which are critical in conditions like Crohn’s Disease. - -In the absence of context-specific information about 'Ractive', it is important to consult the original source documents or related scientific literature for precise insights into this species’ characteristics and role within the biological system being modeled." -mw42054cd7_17af_46da_970c_7f99151906ad,STAT3,STAT3,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context and general knowledge, here is the background information about STAT3: - -### General Background on STAT3: -STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that is pivotal in transmitting signals from the cell surface to the nucleus. It is part of the STAT protein family and is involved in cellular processes such as cell growth and apoptosis. - -### Biological Function: -STAT3 is primarily activated through phosphorylation—a process in which a phosphate group is added, often leading to a functional change of the protein. Once phosphorylated (pSTAT3), it dimerizes and translocates to the nucleus where it can influence the expression of a variety of genes. - -### Role in Pathways: -STAT3 is a critical component of the JAK-STAT signaling pathway, which is a chain of interactions between proteins in a cell, and is also involved in mediating responses to cytokines and growth factors. In this context, it appears specifically related to IL-6 signaling. IL-6 is a cytokine that can induce the phosphorylation of STAT3, leading to its activation and subsequent gene transcription that drives processes like differentiation of lymphocytes and expression of acute-phase proteins such as C-reactive protein (CRP). - -### Interactions with Other Molecules: -STAT3 interacts with various molecules primarily through the phosphorylation process. It is closely tied to components like gp130 and sIL-6R in the IL-6 signaling cascade. In response to IL-6, the receptor complex that includes IL-6Rα and gp130 becomes activated, leading to JAK activation and subsequent phosphorylation of STAT3. - -### Importance in Biological Model: -Within the context of the provided information, STAT3 plays a significant role in diseases such as Crohn's disease, where its phosphorylated form, pSTAT3, has been observed in colon biopsies. This suggests that STAT3 might be central to inflammatory signaling pathways that underpin certain diseases, making it a potential target for therapeutic interventions. - -This inferred understanding aligns with its general role in bodily immunity and inflammation, highlighting its potential implications in both research and clinical settings relevant to cytokine signaling and immune response regulation." -mw39c2e431_fdc3_4964_be29_6ca856620b1b,pSTAT3,pSTAT3,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context and general knowledge, here's an overview of pSTAT3: - -### Biological Function: -- pSTAT3, or phosphorylated STAT3, is part of the STAT (Signal Transducer and Activator of Transcription) family of transcription factors. These proteins are crucial for relaying information from extracellular signals to the cell nucleus, where they influence gene expression. -- Upon activation, STAT3 becomes phosphorylated, hence pSTAT3, which allows it to dimerize (pair with another STAT3 molecule), translocate to the nucleus, and bind to DNA, promoting the transcription of target genes. - -### Role in Pathways: -- pSTAT3 is instrumental in the IL-6 signaling pathway. IL-6 is a cytokine that, upon binding to its receptors, activates the Janus kinase (Jak) pathway, which in turn phosphorylates STAT3. -- The context describes a trans-signaling pathway involving IL-6 and its soluble receptor sIL-6Rα, with pSTAT3 being a downstream effector of this pathway. -- This pathway is crucial for various cellular responses, including differentiation, survival, and proliferation, especially in immune and inflammatory responses. - -### Interactions with Other Molecules: -- The phosphorylation of STAT3 is a result of interactions with upstream kinases like Jak, following cytokine receptor activation (e.g., by IL-6/sIL-6Rα). -- pSTAT3 is known to interact with various co-factors and DNA sequences to regulate the expression of genes involved in inflammation and immune responses. -- It is hinted that pSTAT3 levels are elevated in inflammatory conditions like Crohn’s disease, indicating interactions with molecules or pathways involved in inflammation. - -### Importance in the Biological System: -- pSTAT3 is a critical mediator in the context of inflammatory diseases, such as Crohn’s disease, where its increased levels in colon biopsies suggest a role in the pathogenesis or progression of these diseases. -- By regulating gene expression in response to cytokine signaling, STAT3, especially in its phosphorylated form, is important for maintaining appropriate immune responses and cellular homeostasis. -- Its role extends beyond normal physiology to pathophysiological conditions, where its dysregulation is often linked to chronic inflammatory states, autoimmune disorders, and even cancers. - -In summary, pSTAT3 is a pivotal molecule within the IL-6 cytokine signaling pathway, acting as a key transcriptional regulator in immune and inflammatory responses. Its heightened activity is associated with pathological conditions, highlighting its importance as a potential therapeutic target in such diseases." -mwd5313618_89eb_4c8c_bc82_66f10f966349,"CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",CRP,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, here is the background information about the species 'CRP (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)': - -1. **Biological Function**: CRP, or C-reactive protein, is a biomarker of inflammation in the body. It is produced by the liver in response to inflammation and its levels increase in the bloodstream during inflammatory processes. - -2. **Role in Pathways**: CRP is primarily associated with the body's immune response to inflammation. It is part of the acute phase response, which is a rapid systemic response to injury, infection, or other inflammatory stimuli. The context suggests that CRP is being used in a model to evaluate inflammation levels, particularly in relation to Crohn’s disease and the effects of anti-inflammatory drugs like tocilizumab. - -3. **Interactions with Other Molecules**: CRP interacts with various components of the immune system. In the context of the document, CRP levels are used to assess the effectiveness of inhibiting IL-6 signaling—a cytokine involved in inflammation by targeting IL-6 or its receptors. Thus, CRP serves as an indicator for the efficacy of this anti-inflammatory strategy. - -4. **Importance in the Biological System Being Modeled**: In the model described, CRP is a critical marker used to validate and predict the outcomes of drug treatments aimed at reducing inflammation, such as those used in Crohn's disease. The model uses CRP as a metric to evaluate the suppression of inflammation due to the therapeutic inhibition of IL-6 signaling pathways. - -In summary, CRP is an important inflammatory marker used in the modeling of immune response and drug efficacy in inflammatory diseases, particularly for evaluating interventions targeting IL-6 signaling." -mw2e464cf3_a09c_4b7c_9f3c_06720016a48e,"sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"From the context provided, it seems that the specific species 'sR' (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) is not directly mentioned or detailed. Thus, I will infer its possible role based on the general context involving related biological components. - -1. **Biological Function:** - - Given the surrounding context of interleukin 6 (IL-6), it is likely that 'sR' refers to a soluble receptor, potentially the soluble IL-6 receptor (sIL-6R). Soluble receptors often function to sequester ligands or modulate signaling pathways by facilitating ligand interaction with cell surface receptors. - -2. **Role in Pathways:** - - 'sR', if it represents sIL-6R, participates in the IL-6 signaling pathways. IL-6 can bind to sIL-6R, forming a complex that further associates with membrane-bound gp130, leading to activation of intracellular signaling pathways such as the JAK/STAT pathway. This pathway is involved in inflammation and the regulation of the immune response. - -3. **Interactions with Other Molecules:** - - 'sR' forms part of the IL-6/sIL-6R complex interacting with gp130, a common receptor subunit involved in IL-6 family cytokine signaling. This complex formation enhances signaling across various tissues, especially when the IL-6 concentration is limited, as seen from the content discussing IL-6 and sgp130 concentrations. - -4. **Importance in the Biological System Being Modeled:** - - If 'sR' represents a soluble receptor interacting with IL-6, it plays a crucial role in modulating IL-6's effects, potentially affecting processes like acute-phase responses, immune function, and inflammation. The model suggests that perturbations in components like sgp130 have minor effects due to concentration differences, implying that the effective modulation of signaling depends heavily on components like sR/sIL-6R and IL-6 interactions. - -In summary, while 'sR' is not explicitly described, it might denote a molecule like the soluble IL-6 receptor within the context of IL-6 signaling pathways, influencing inflammatory and immune responses." -mw36ea78c1_ed71_4def_96d3_857a442d7195,CRPExtracellular,CRPExtracellular,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, it seems that specific information about the species 'CRPExtracellular' (ID: mw36ea78c1_ed71_4def_96d3_857a442d7195) within the context of mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e is not explicitly detailed. However, we can infer some information based on the general role of C-reactive protein (CRP) within biological systems and its mention in the context. - -1. **Biological Function**: CRP, or C-reactive protein, is a substance produced by the liver in response to inflammation. Its primary function is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via the C1Q complex, thus playing an important role in the body's immune response by enhancing the ability to clear pathogens and damaged cells. - -2. **Role in Pathways**: CRP is typically involved in the acute phase response to inflammation. Its production increases in response to pro-inflammatory cytokines like interleukin-6 (IL-6), as indicated by the context mentioning IL-6 and CRP in relation to various treatments aiming to modulate inflammation pathways. - -3. **Interactions with Other Molecules**: The interaction between CRP and IL-6 is highlighted, with IL-6 being a key cytokine that stimulates the production of CRP. The context also discusses various treatment strategies that involve targeting IL-6 or its receptors to reduce inflammation and subsequently decrease CRP levels, demonstrating CRP's role as a marker for inflammatory activity and the effectiveness of anti-inflammatory treatments. - -4. **Importance in the Biological System Being Modeled**: The context suggests that CRP is used as a biomarker for inflammation in Crohn’s disease, and its levels are used to monitor the effectiveness of treatment strategies that target IL-6 signaling. Therefore, CRP is a key output in the model being discussed, representing the systemic inflammatory response and providing feedback on the effectiveness of therapeutic interventions. - -In conclusion, while specific details about the species 'CRPExtracellular' in the mentioned context are not given, its role as a marker of inflammation and its regulation through pathways involving IL-6 are central to the model's focus on understanding and predicting the outcomes of therapeutic interventions in inflammatory conditions like Crohn’s disease." -mw147d30ec_478e_4090_b496_128a131d29eb,"sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sgp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the provided context, the species labeled as 'sgp130' (associated with ID: mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e) seems to be a fusion protein designed to interact with components involved in IL-6 signaling pathways. Here's a summary of its relevant aspects: - -- **Biological Function:** - - sgp130 functions as an inhibitor of IL-6 trans-signaling. It is a fusion protein that combines the extracellular portion of gp130 with the Fc region of human IgG1, termed sgp130Fc. This modification allows sgp130 to bind to the IL-6/sIL-6Rα complex. - -- **Role in Pathways:** - - It is involved in the IL-6 trans-signaling pathway. IL-6 is a cytokine that plays a crucial role in immune response and inflammation. The trans-signaling pathway involves the binding of IL-6 to a soluble receptor sIL-6Rα, which then associates with gp130 to signal. - -- **Interactions with Other Molecules:** - - sgp130 interacts specifically with the IL-6/sIL-6Rα complex. The context suggests that sgp130 binds this complex with similar affinity to natural gp130, aiming to inhibit downstream signaling events such as CRP (C-reactive protein) and pSTAT3 production in the gut. - -- **Importance in the Biological System:** - - Despite its designed purpose, simulations and sensitivity analyses indicate that sgp130 (as sgp130Fc) has relatively low impact on the biological system being modeled, particularly when used as a therapeutic agent for conditions like Crohn’s disease. Its effectiveness is noted only at very high and frequent doses due to the high baseline levels of sgp130 naturally present, in contrast to the low concentration of IL-6. - -In summary, sgp130 is primarily modeled to inhibit IL-6 trans-signaling but poses challenges as a therapeutic due to its excess presence compared to IL-6, limiting its potential impact on the system without large dosage increases." -mwab41493c_6349_45f1_a226_3030cfed0e06,"sR_IL6_sgp130 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",sR_IL6_sgp130,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"Based on the context provided, specific mentions of the species named 'sR_IL6_sgp130' (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2) are not directly available. However, we can infer its nature and potential role based on the information about similar molecules provided in the document. - -1. **Biological Function**: The context discusses sgp130, which is known to be a soluble form of the gp130 receptor. These soluble receptors, like sgp130, are known to inhibit IL-6 trans-signaling. In general, soluble receptors can bind cytokines or cytokine complexes in the extracellular environment, preventing them from triggering cell surface receptors and subsequent intracellular signaling cascades. - -2. **Role in Pathways**: The sgp130 serves as an inhibitor in the IL-6 signaling pathway, particularly in IL-6 trans-signaling. This pathway is involved in various inflammatory and immune processes. By inhibiting this pathway, sgp130 could potentially reduce inflammatory responses, which is particularly relevant in conditions like Crohn’s disease, as mentioned in the context. - -3. **Interactions with Other Molecules**: The sgp130 binds to the IL-6/sIL-6Rα complex. This specific interaction is crucial for its role as an inhibitor in the pathway. It prevents the IL-6 complex from interacting with membrane-bound gp130, thus blocking downstream signaling events. - -4. **Importance in the Biological System Being Modeled**: In the biological system modeled, sgp130 appears to represent a regulatory component that modulates the IL-6 signaling pathway. Its presence in high baseline levels as compared to free IL-6 indicates a natural buffering or regulatory role in maintaining homeostasis in the signaling environment. It suggests that significant therapeutic modulation (e.g., large doses of sgp130Fc) would be needed to observe pronounced effects. - -While specific details about 'sR_IL6_sgp130' (#2) are not available, the understanding of sgp130's role in IL-6 trans-signaling and its functional characterization can be reasonably extrapolated to gain insights into this species' potential biological importance." -mwf405687b_7401_44ec_a0d6_4a2b35c13e8a,"Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab_sR,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided does not contain specific information about the biological species or molecule named 'Ab_sR (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' or its ID 'mwf405687b_7401_44ec_a0d6_4a2b35c13e8a'. Given the lack of direct details in the documents, I can infer potential characteristics of 'Ab_sR' based on common biological concepts and patterns discussed in similar contexts. - -1. **Biological Function**: Given the use of ""Ab"" in the name, 'Ab_sR' may refer to an antibody-related species, possibly a soluble receptor (sR) or an antibody-receptor complex. In many biological systems, antibodies play crucial roles in immune responses, binding to specific antigens to neutralize them or mark them for destruction by other immune cells. - -2. **Role in Pathways**: In the context of systems biology models that often study signaling and immune pathways, 'Ab_sR' may be involved in modulating signaling cascades. Since the documents mention the IL-6/sIL-6Rα complex, 'Ab_sR' might participate in pathways related to cytokine signaling, such as the interleukin-6 (IL-6) pathway, which is crucial in inflammation and immune regulation. - -3. **Interactions with Other Molecules**: Given the similarities to components like IL-6 and sIL-6Rα, 'Ab_sR' may interact with these molecules either as a part of a complex or influence their activity. For instance, antibodies or their fragments (like those potentially represented by 'Ab_sR') can bind to cytokines or their receptors, affecting the downstream signaling events. - -4. **Importance in the Biological System Being Modeled**: Systems biology models often explore the dynamics and regulation of complex biochemical networks. If 'Ab_sR' is involved in cytokine-receptor interactions, it can be important in modulating inflammatory responses or immune system function, potentially making it a target for therapeutic interventions in diseases characterized by inflammation or immune dysfunction. - -To summarize, while 'Ab_sR' is not directly described in the context provided, it is likely associated with antibody or receptor functions within signaling or immune pathways similar to those of IL-6/sIL-6Rα in the documents referenced. If additional data is available, it could help refine or confirm these inferences." -mw3667a5e1_02c9_44a0_acb4_b0431faa822d,"Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided does not offer any specific information about the species or molecule identified as 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)' within the document. However, based on the excerpts, it is possible to infer the following general insights regarding similar biological components: - -1. **Biological Function**: The molecule labeled 'Ab' is likely an antibody, which are proteins used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. In this context, 'Ab' might refer to an antibody targeting a particular biological pathway or molecule. - -2. **Role in Pathways**: Antibodies are typically involved in immune response pathways. The document mentions interactions that involve the cytokine IL-6 and its receptor, IL-6Rα. It is possible that 'Ab' could be an antibody aimed at either IL-6 or IL-6Rα, or their complex, to modulate immune responses. - -3. **Interactions with Other Molecules**: The document excerpt references the targeting of IL-6 or its receptor, sIL-6Rα. These molecules play roles in inflammatory processes, indicating that 'Ab' might interact with these molecules and potentially be used to suppress inflammation or other immune responses. - -4. **Importance in the Biological System**: Antibodies like 'Ab' are important in a biological system because they can help to precisely modulate pathways that involve cytokines like IL-6, which are crucial in inflammatory and immune responses. This suggests its relevance in therapeutic interventions, especially in conditions where regulating immune activity is necessary. - -An understanding of similar antibodies, like anti-IL-6 or anti-IL-6R antibodies, typically helps in reducing inflammation and is useful in treating conditions like rheumatoid arthritis and other autoimmune diseases. - -In conclusion, while there is no direct information about 'Ab (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)', it can be inferred to be an antibody with potential functions related to immune modulation, likely within pathways involving IL-6 and its receptor(s)." -mw772cbf20_3fc1_4800_ae59_77884f1ae333,Ab_R,Ab_R,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The context provided does not specifically mention the species 'Ab_R' with the ID mw772cbf20_3fc1_4800_ae59_77884f1ae333 located in mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e. However, the documents discuss the use of antibodies in modulating interleukin pathways, specifically targeting IL-6 and its receptor variants. - -Based on general knowledge and the context provided, Ab_R might represent an antibody related to the regulation or interaction with the IL-6 pathway or its receptors. - -1. **Biological Function**: If Ab_R is an antibody, its primary function might be to bind to specific targets, such as antigens or receptors like IL-6, sIL-6Rα, or the IL-6/IL-6R complex, to modulate immune responses or inflammatory pathways. - -2. **Role in Pathways**: An antibody resembling Ab_R in this context could be involved in reducing inflammation by blocking the interaction between IL-6 and its receptor, preventing downstream signaling and overactivation of the immune response. This could be relevant in the context of diseases with inflammatory components. - -3. **Interactions with Other Molecules**: Ab_R might interact with proteins like IL-6, its receptors, or complexes such as IL-6/IL-6R, aiming to modulate their activity or presence in the system, leading to changed concentrations of downstream inflammatory markers such as C-reactive protein (CRP). - -4. **Importance in the Biological System**: In the modeled biological system, such an antibody would be crucial for understanding and predicting therapeutic responses in diseases involving chronic inflammation, autoimmune conditions, or cancer. Its efficacious application could provide insights into novel therapeutic strategies. - -While specific information about 'Ab_R' is not available from the context, the inference aligns it with potentially important roles in immunological regulation through mechanisms of blocking or interacting with cytokine pathways, as seen in therapeutic antibodies targeting the IL-6 signaling axis." -mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf,"Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)",Ab_sR_IL6,mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e,"The provided context lacks specific information about the species identified as 'Ab_sR_IL6 (mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, #2)'. However, based on general knowledge and the context concerning IL-6 and its soluble receptor sIL-6Rα, we can infer the following: - -1. **Biological Function**: The molecule 'Ab_sR_IL6' likely functions as an antibody targeting the IL-6/sIL-6R complex. IL-6 is a cytokine involved in inflammatory and immune responses, and sIL-6R is its soluble receptor form. Antibodies targeting these molecules are typically designed to modulate the immune response, particularly in diseases characterized by excessive inflammatory signaling such as Crohn’s Disease. - -2. **Role in Pathways**: This antibody likely plays a role in blocking or modulating the pathway involving IL-6-mediated signaling. By binding to IL-6 and/or sIL-6R, it prevents their interaction with gp130, a co-receptor necessary for signal transduction, thereby inhibiting downstream signaling effects like the activation of STAT3 and the subsequent transcription of inflammatory genes. - -3. **Interactions with Other Molecules**: The primary interaction of 'Ab_sR_IL6' would be with IL-6 and sIL-6Rα, limiting their availability to participate in inflammatory signaling. This kind of interaction is often employed to reduce levels of inflammatory mediators like C-reactive protein (CRP) in the circulation. - -4. **Importance in the Biological System**: In the context of the document, which seems to be related to inflammatory diseases such as Crohn's Disease, the importance of 'Ab_sR_IL6' would be in its potential therapeutic application. By reducing IL-6 signaling, it could help in controlling inflammation and alleviating disease symptoms. - -In summary, while specific details about 'Ab_sR_IL6' are not provided, its naming and context imply it is an antibody targeting key components of the IL-6 signaling pathway with potential significance in therapeutic interventions for inflammatory conditions." -mw7becb5fe_8da8_4285_a821_0d77ad811b62,"sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR_IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The species 'sR_IL6' (ID: mw7becb5fe_8da8_4285_a821_0d77ad811b62) located in 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5' likely refers to a soluble receptor component involved in IL-6 signaling pathways. Although the provided context does not give explicit details about 'sR_IL6', we can infer its role based on the mention of 'sIL-6R' and related IL-6 signaling pathways: - -1. **Biological Function**: 'sR_IL6' is likely a soluble form of the IL-6 receptor, similar to 'sIL-6R'. Soluble receptors often serve to modulate cytokine signaling, either by extending the half-life of the cytokine in circulation, facilitating its transport, or altering its activity. - -2. **Role in Pathways**: The context suggests that IL-6 signals through both classical and trans-signaling pathways. In the context of immune regulation and Crohn's disease, the IL-6/sIL-6Rα complex is involved in the modulation of inflammatory responses. 'sR_IL6' is expected to participate in these pathways, potentially influencing the interaction with sgp130, a natural inhibitor of the trans-signaling route. - -3. **Interactions with Other Molecules**: 'sR_IL6' would interact with IL-6, forming complexes that could be sequestered by sgp130, as well as interact with factors involved in immune signaling, such as STAT3, CRP, and possibly others involved in downstream signaling and gene transcription related to immune modulation. - -4. **Importance in the Biological System**: The role of such soluble receptors is crucial in modulating the availability and activity of cytokines like IL-6. They can influence the strength and duration of signaling in different compartments, vital for maintaining balance in immune responses, particularly in diseases like Crohn's where cytokine signaling can be dysregulated. - -Based on this inference, 'sR_IL6' appears to be an important modulator within the IL-6 signaling network potentially involved in regulatory mechanisms relevant to inflammation and immune response in the context of Crohn’s disease." -mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca,"gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",gp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, the species 'gp130' is involved in the interleukin-6 (IL-6) signaling pathway. Gp130 plays a crucial role as a signal transducer for the IL-6 family of cytokines. It forms a complex with the IL-6/IL-6 receptor (IL-6R) to propagate intracellular signaling leading to various biological responses. - -1. **Biological Function**: Gp130 is involved in mediating the effects of cytokines, particularly IL-6. It is a part of the receptor complex that includes the IL-6 receptor and gp130. When IL-6 binds to its receptor, gp130 is recruited to form a signaling complex, which then initiates downstream signaling pathways such as JAK/STAT, MAPK, and PI3K/Akt. - -2. **Role in Pathways**: Gp130 is central to the IL-6 signaling pathway, which is involved in immune responses, inflammation, and cell survival. It is indispensable for the transmission of signals that lead to the activation of transcription factors such as STAT3, which can then affect the expression of various genes involved in inflammatory responses. - -3. **Interactions with Other Molecules**: Gp130 interacts specifically with the IL-6/IL-6R complex to transmit cytokine-mediated signals. Additionally, soluble forms of gp130 (sgp130) act as natural inhibitors of IL-6 signaling by binding to IL-6/soluble IL-6R complexes, thereby preventing them from interacting with membrane-bound gp130. - -4. **Importance in the Biological System**: In the context of inflammatory diseases such as Crohn's disease, modulation of gp130 and its associated signaling pathways represents a potential therapeutic strategy. Soluble gp130 (sgp130Fc), a fusion protein combining the extracellular portion of gp130 with an Fc region, has been studied for its ability to inhibit IL-6 trans-signaling, highlighting its therapeutic potential in conditions characterized by excessive or dysregulated IL-6 activity. - -Overall, gp130 is a critical component of the IL-6 signaling pathway, with its function as both a necessary signal transducer and a target for therapeutic inhibition in inflammatory diseases." -mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9,"R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",R_IL6_gp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context and information provided, the specifics about the species named 'R_IL6_gp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' are not directly detailed. However, by piecing together related information and general knowledge, we can infer some aspects of its characteristics and role in biological systems: - -1. **Biological Function**: 'R_IL6_gp130' likely represents the interaction or complex involving the interleukin-6 (IL-6) signaling pathway and the gp130 co-receptor. IL-6 is a cytokine involved in immune responses, inflammation, and hematopoiesis. Gp130 is a signal transducer for cytokines in the IL-6 family and plays a crucial role in transmitting signals from cytokine receptors. - -2. **Role in Pathways**: The IL-6/gp130 complex is essential in the IL-6 signaling pathway, which influences various biological processes including inflammation, immune response, and acute phase reactions. This pathway can operate through classical signaling using membrane-bound receptors or trans-signaling with soluble receptors and receptors like gp130. - -3. **Interactions with Other Molecules**: The IL-6 signaling pathway involves interactions between IL-6, soluble IL-6 receptor (sIL-6R), and gp130. It is noted that soluble gp130 (sgp130) can inhibit IL-6 trans-signaling, which suggests that 'R_IL6_gp130' might be relevant in modulating or forming complexes crucial for either inhibiting or promoting the IL-6 signal. - -4. **Importance in Biological System**: In the context of the system being modeled (likely involving conditions like Crohn's disease), targeting the IL-6/gp130 pathway may have therapeutic implications. Efforts such as using sgp130Fc fusion proteins to inhibit IL-6 trans-signaling highlight the importance of understanding and manipulating this complex in disease models for potential treatment strategies. - -Therefore, 'R_IL6_gp130' in this context probably signifies a key component or step within the IL-6 signaling pathway, with potential roles in modulating inflammatory responses, significant to modeling diseases like Crohn's disease." -mw6cce2109_0e32_4dd9_98ec_41173e8ef07d,"Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",Ractive,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The provided context does not directly reference the species named 'Ractive (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)' or its ID: mw6cce2109_0e32_4dd9_98ec_41173e8ef07d. However, we can attempt to infer its possible characteristics and role based on the general information available in the context, which focuses on IL-6-mediated immune regulation in Crohn's Disease, using a multiscale model. - -1. **Biological Function:** - The document is centered around the regulation of IL-6, interleukin-6, which is an important cytokine involved in inflammatory and immune responses. While Ractive itself is not mentioned, it could potentially be related to or a component interacting within the IL-6 signaling pathways. - -2. **Role in Pathways:** - Since the context enlightens the importance of the IL-6/sIL-6Rα complex in IL-6 signaling, Ractive might play a role in a related or auxiliary pathway, possibly as a regulatory or signaling molecule. - -3. **Interactions with Other Molecules:** - The IL-6 signaling pathway involves interactions between IL-6, IL-6 receptors, sIL-6Rα (soluble IL-6 receptor), and antibodies like tocilizumab (anti-IL-6Rα). It's plausible that Ractive could interact with similar molecules or influence the pathway indirectly. - -4. **Importance in the Biological System:** - Given the context's focus on immune regulation and Crohn's Disease, Ractive could be assumed as an important component in the signaling or regulatory mechanisms within this biological model, potentially influencing cytokine behavior, immune response modulation, or drug interactions. - -In summary, while there's no specific information on Ractive, its inferred role might be associated with IL-6 signaling, immune pathway interactions, or drug (such as antibody) responses within the described model of immune regulation." -mw2b255f94_8018_4b99_bde8_918eeac45446,"STAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",STAT3,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the available context from the provided documents, STAT3 appears to refer to ""signal transducer and activator of transcription 3"". This molecule is a critical component in the JAK/STAT signaling pathway, which is involved in transducing extracellular signals into cellular responses. The context mentions that phosphorylation of STAT3 is important, suggesting that it becomes activated through the addition of a phosphate group. Activated or phosphorylated STAT3 (pSTAT3) can then translocate to the nucleus where it functions as a transcription factor regulating the expression of various genes. - -**Biological Function:** -STAT3 plays a key role in mediating the effects of various cytokines and growth factors by regulating gene expression. It is involved in controlling multiple cellular processes such as cell growth, apoptosis, and differentiation. - -**Role in Pathways:** -STAT3 is a central player in the JAK/STAT signaling pathway. It is specifically mentioned in the context of IL-6 signaling, where it is activated downstream of interleukin-6 receptor engagement, which can involve both classical and trans-signaling mechanisms. - -**Interactions with Other Molecules:** -STAT3 interacts with IL-6 and its receptors (such as sIL-6R and gp130), and phosphorylation of STAT3 can be triggered by cytokines binding to these receptors. The document implies interactions with components like C-reactive protein (CRP) and possibly engagements involving soluble forms of receptors like sgp130, which can modulate signaling. - -**Importance in the Biological System Being Modeled:** -STAT3's significance in the biological model investigated (likely related to inflammatory diseases like Crohn’s disease) lies in its role in mediating cytokine signaling that could lead to inflammation and other immune responses. The upregulation of phosphorylated STAT3 in specific tissue biopsies, such as those from the colon in Crohn’s disease, suggests its involvement in inflammatory pathogenic mechanisms. - -Overall, STAT3 is a crucial component in understanding how intracellular pathways translate external signals into gene expression changes that affect biological outcomes and diseases." -mw48867e93_f170_44e8_ac7a_185b23e1bf3b,"pSTAT3 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #2)",pSTAT3,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The provided context does not contain detailed or specific information about the species pSTAT3 identified by the ID mw48867e93_f170_44e8_ac7a_185b23e1bf3b, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5. Therefore, I will provide a summary based on general knowledge about pSTAT3 and its role in biological systems. - -**Background Information on pSTAT3:** - -- **Biological Function:** - pSTAT3 refers to the phosphorylated form of the STAT3 protein, which stands for Signal Transducer and Activator of Transcription 3. STAT3 is a transcription factor that, when phosphorylated, becomes activated and dimerizes. This activated dimer can then translocate to the nucleus to modulate the expression of specific target genes. - -- **Role in Pathways:** - STAT3 is primarily involved in the JAK-STAT signaling pathway. Upon activation, typically through cytokine signaling such as IL-6, STAT3 is phosphorylated by Janus kinases (JAKs). pSTAT3 plays a crucial role in mediating responses to extracellular signaling and is involved in various biological processes such as cell growth, differentiation, and survival. - -- **Interactions with Other Molecules:** - pSTAT3 interacts with JAKs as part of its activation. It is also involved in crosstalk with other signaling molecules and pathways, including IL-6, sIL-6R (soluble IL-6 receptor), and gp130. These interactions facilitate a range of cellular responses, including modulation of immune response, inflammation, and cellular proliferation. - -- **Importance in the Biological System:** - pSTAT3 is an important mediator in immune responses and inflammation. It has been implicated in various diseases, including inflammatory bowel diseases like Crohn's disease, where increased levels of pSTAT3 have been observed in affected tissues. It also plays a role in cancer progression, where aberrant STAT3 activity contributes to tumorigenesis. - -In the context of the document, mention of pSTAT3 suggests its potential involvement in IL-6 signaling pathways, possibly related to immune and inflammatory responses as well as transcriptional regulation of genes relevant to the conditions being discussed (e.g., Crohn’s disease or similar inflammatory conditions)." -mw0083d743_836f_4238_a17f_4602193d5bc0,geneProduct,geneProduct,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The provided context does not specifically describe the species named 'geneProduct' with the ID 'mw0083d743_836f_4238_a17f_4602193d5bc0' located in 'mwe9501423_9fb4_494b_b5b6_288f3fcb17b5'. However, based on the general context and common knowledge within systems biology, we can infer some plausible information about 'geneProduct' in relation to similar biological components: - -1. **Biological Function**: Given that 'geneProduct' is mentioned in the context of IL-6 signaling and STAT3 activation, it could be a gene product related to cytokine signaling pathways. Gene products involved in this pathway typically play roles in immune responses, inflammation, cell survival, and proliferation. - -2. **Role in Pathways**: The context includes references to IL-6, sIL-6R, and associated signaling pathways, such as those involving STAT3 and SOCS. 'geneProduct' may be involved in modulating these pathways, possibly influencing downstream effects such as gene transcription. - -3. **Interactions with Other Molecules**: 'geneProduct' might interact with key proteins and receptors in the IL-6 signaling pathway, such as IL-6, sIL-6R, gp130, and sgp130. These interactions could be crucial for the regulation and fine-tuning of the signaling pathway. - -4. **Importance in the Biological System**: If 'geneProduct' participates in IL-6 signaling, it could be important for processes like acute phase responses, immune regulation, and potentially in the context of diseases where IL-6 plays a role, such as autoimmune disorders or chronic inflammatory conditions. - -Without specific information, these inferences are speculative but based on common roles and interactions seen within such pathways." -mwd31f52cc_04e7_40e0_885f_c7b2d9e62215,"sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is specific mention of an interaction between sR and IL-6. Although the document does not explicitly describe the species labeled as 'sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)', we can infer its potential role and importance by drawing parallels to similar entities mentioned in the system's model involving IL-6 signaling. - -### Inferred Information about sR: - -- **Biological Function**: - - The 'sR' is likely a soluble receptor or receptor component involved in the IL-6 signaling pathway, given its contextual relationship with IL-6 and similar naming conventions to 'sIL-6R' and its complex with IL-6 ('IL-6:sR'). - -- **Role in Pathways**: - - It seems to participate in modulating IL-6 activity. The mention of 'IL-6:sR' implies that the sR might form complexes with IL-6, influencing the signaling dynamics, possibly acting as a decoy receptor or as a mediator that facilitates or modifies downstream signaling. - -- **Interactions with Other Molecules**: - - The document discusses complexes such as 'IL-6:sR' and 'IL-6:sR:sgp130'. This suggests that sR interacts directly with IL-6 and possibly with other soluble components like sgp130, which is known to modulate IL-6 trans-signaling. - -- **Importance in the Biological System**: - - While sR's specific function was not detailed, its involvement in forming complexes such as 'IL-6:sR' suggests a regulatory role in the IL-6 pathway, which is crucial for inflammatory and immune responses. - - The interaction between sR and IL-6 may have implications for therapeutic targets, particularly in conditions where IL-6 signaling is dysregulated. - -In summary, 'sR' likely plays a critical part in the IL-6 signaling pathway, influencing the biological effects of IL-6 through complex formation and interaction with other soluble proteins like sgp130. Understanding its role would be important for modeling systemic inflammatory responses and potentially informs therapeutic strategies targeting IL-6 pathways." -mw2c9b0499_3325_4394_8af3_bbf653a944a0,"IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, IL-6 (likely referring to the cytokine Interleukin-6) is a significant player in the immune regulation associated with Crohn’s disease. Here is a summary of the relevant information extracted about IL-6: - -1. **Biological Function**: IL-6 is a cytokine that plays a critical role in immune responses. It is involved in the survival of T-cells and contributes to their apoptosis resistance, especially in the lamina propria, a tissue layer in the intestines. This function is particularly relevant in the context of inflammatory diseases such as Crohn's disease. - -2. **Role in Pathways**: IL-6 signaling can occur through two main pathways: - - The **classical pathway**, mediated by a membrane-bound IL-6 receptor (IL-6Rα). - - The **trans-signaling pathway**, mediated by a soluble form of the IL-6 receptor (sIL-6Rα). Both pathways involve the recruitment of a membrane-bound gp130 coreceptor to form an active complex that leads to downstream signaling events, including the phosphorylation of Janus kinase (Jak) family proteins and the activation of signal transducer and activator of transcription 3 (STAT3). - -3. **Interactions with Other Molecules**: IL-6 interacts with its receptor IL-6Rα (both in its membrane-bound and soluble forms) to initiate signaling. In the classical signaling pathway, the IL-6/IL-6Rα complex recruits gp130 to form a functional receptor complex. This interaction initiates a cascade, leading to the activation of downstream signaling molecules, including Jak and STAT3. - -4. **Importance in the Biological System**: IL-6 is crucial in the modulation of immune responses, which are essential in the context of inflammatory diseases like Crohn’s disease. It enhances the survival of T-cells, contributing to the chronic inflammation characteristic of this condition. The trans-signaling pathway, involving the soluble IL-6Rα, is particularly noted for its importance in disease, highlighting IL-6's role in promoting inflammatory pathways. - -Overall, IL-6 is depicted as a pivotal cytokine in driving the immune responses that characterize inflammatory diseases, and its pathways and interactions are potential targets for therapeutic intervention." -mwd65b5b39_dc1b_4e77_a999_67277a880e5e,"sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sgp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The species or molecule 'sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)' seems to be referring to a soluble form of gp130, which is a component of the IL-6 signaling pathway. Here is a summary of the relevant background information based on the provided excerpts: - -1. **Biological Function**: - - sgp130 functions as an inhibitor of IL-6 trans-signaling, which is a process involving the IL-6 signaling pathway. This occurs when sgp130 binds to the IL-6/sIL-6Rα complex, effectively blocking its ability to signal. - -2. **Role in Pathways**: - - sgp130 is involved in the IL-6 signaling pathway, particularly in the inhibition of IL-6 trans-signaling. This pathway is significant in inflammation and immune response, and it involves interactions with the soluble IL-6 receptor (sIL-6Rα). - -3. **Interactions with Other Molecules**: - - sgp130 interacts with the IL-6/sIL-6Rα complex. By binding to this complex, sgp130 prevents IL-6 from engaging with membrane-bound gp130, thus inhibiting downstream signaling events. - -4. **Importance in the Biological System Being Modeled**: - - In the modeling context provided, altering the levels of sgp130 has minimal effect on the system due to its high baseline levels compared to the much lower concentrations of free IL-6. This suggests that while sgp130 is present in excess, significant changes in its levels are required to observe an impact on system outputs. - - The effectiveness of sgp130-based therapies appears limited under normal conditions and requires high doses for observable effects, particularly in the suppression of CRP (C-reactive protein) levels and pSTAT3 in the gut. - - The sensitivity analysis of the system model indicates that sgp130 is among the least influential parameters for output biomarkers, suggesting that targeting IL-6 and its receptor may be more effective for therapeutic interventions. - -Overall, sgp130 plays a regulatory role in the IL-6 signaling pathway by acting as a natural inhibitor, but in the context of the model discussed, its predominant presence makes it less impactful for modifying system dynamics without high interventions." -mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3,"sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",sR_IL6_sgp130,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the context provided, there is no specific mention of the species ""sR_IL6_sgp130 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)"" with the ID ""mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3."" However, we can infer its role and importance based on the information regarding similar biological components described in the context. - -### Inferred Background Information on sR_IL6_sgp130: - -1. **Biological Function:** - - The molecule seems to relate to the signaling pathway of IL-6 (Interleukin-6), a cytokine important in immune response. - - sR_IL6_sgp130 likely involves binding interactions similar to natural sgp130, which acts to inhibit IL-6 signaling by interfering with the IL-6/sIL-6R complex. - -2. **Role in Pathways:** - - It may be involved in pathways such as IL-6 trans-signaling, which is mediated by the soluble IL-6 receptor (sIL-6R) and amplifies responses, particularly in diseases like Crohn's. - - It could potentially modulate signaling cascades involving STAT3 (Signal Transducer and Activator of Transcription 3), as IL-6 activates STAT3 through its receptor complexes. - -3. **Interactions with Other Molecules:** - - Likely interacts with components such as IL-6, sIL-6Rα, and sgp130 to modulate signaling. - - Its interaction may focus on forming a complex that either facilitates or inhibits further downstream signaling, affecting the activity of proteins like pSTAT3 (phosphorylated STAT3). - -4. **Importance in the Biological System:** - - Given the high baseline level of sgp130 relative to free IL-6, sR_IL6_sgp130 may play a role in maintaining a steady state of signaling through sequestration of signaling complexes. - - Its importance could be in contexts requiring modulation of IL-6 activity, either as a natural response or therapeutic intervention, particularly in inflammatory conditions. - -This inference is based on the role of similar molecules and the described importance of IL-6 signaling modulation in immunological and inflammatory contexts." -mwf7796221_1fea_4274_a93e_c00adbf5778c,"Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no direct or specific information about the species 'Ab (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)'. However, we can infer what this species might be based on general knowledge about similar biological components mentioned in the context. - -From page 5 of the document, we see references to ""anti-IL-6 Ab"" and interactions with ""IL-6Rα/sIL-6Rα"" complexes, which suggest that 'Ab' could potentially be an antibody, possibly involved in targeting IL-6 or its receptor sIL-6Rα in the biological system being studied. - -**Inferred Biological Function of Ab:** -- 'Ab' is likely an antibody that interacts with IL-6 or IL-6Rα. Antibodies are proteins produced by the immune system that can bind to specific antigens, such as proteins on pathogens or other molecules like interleukins. - -**Role in Pathways:** -- The context mentions dose-response changes impacting serum CRP (C-reactive protein), indicating that 'Ab' might play a role in inflammatory pathways, particularly associated with modulating the immune response. - -**Interactions with Other Molecules:** -- If 'Ab' is an anti-IL-6 antibody, its primary interaction would be with interleukin-6 (IL-6) and its receptor complex, IL-6/sIL-6Rα. This interaction can impede the IL-6 signaling pathway, which is involved in inflammation and immune regulation. - -**Importance in the Biological System:** -- The efficacy of 'Ab' in modulating serum CRP levels implies it holds significance in controlling inflammatory responses, potentially offering therapeutic benefits in conditions characterized by excessive inflammation, such as inflammatory bowel diseases or other chronic inflammatory conditions. - -This inferred role highlights the importance of 'Ab' in potentially therapeutic contexts where modulation of specific cytokine pathways is desired." -mw5d764bb8_5693_4ac8_9557_f65992cc5eb0,"Ab_sR (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab_sR,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"The context provided does not include any specific mention of the species named 'Ab_sR' (ID: mw5d764bb8_5693_4ac8_9557_f65992cc5eb0, located in mwe9501423_9fb4_494b_b5b6_288f3fcb17b5). Therefore, I will infer what this species might be based on general knowledge and the context provided. - -The context provided mentions interactions around IL-6, sIL-6R (soluble interleukin-6 receptor), and the IL-6/sIL-6R complex, which are significant components in the IL-6 signaling pathway. The mention of molecules such as CRP (C-reactive protein) suggests it is related to inflammatory responses. - -Given general biological knowledge, 'Ab_sR' could be hypothesized to represent an antibody or another protein involved in regulating or interacting with soluble receptors like sIL-6R. These soluble receptors often participate in signaling pathways where they modulate the activity of cytokines like IL-6. - -- **Biological Function**: 'Ab_sR' might function as a regulator in the IL-6 signaling pathway. -- **Role in Pathways**: It could play a role in modulating the inflammatory response or could be involved in the same pathway as IL-6/sIL-6R by affecting their interaction or function. -- **Interactions with Other Molecules**: It could potentially interact with IL-6, sIL-6R, or related complexes to modulate signaling and downstream effects such as CRP production. -- **Importance in the Biological System**: If it is analogous to components like antibodies or receptor regulators, its importance could lie in its potential to modulate immune responses and inflammation. - -Conclusively, without explicit details from the text, we extrapolate that 'Ab_sR' might be involved in related pathways and interactions as a regulatory molecule based on the IL-6/sIL-6R context and general knowledge of similar biological systems." -mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2,"Ab_sR_IL6 (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3)",Ab_sR_IL6,mwe9501423_9fb4_494b_b5b6_288f3fcb17b5,"Based on the provided context, there is no specific mention of the biological species or molecule named 'Ab_sR_IL6' (mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, #3). However, we can infer some relevant details from the general context regarding IL-6 and related pathways. - -1. **Biological Function**: - - IL-6 is a cytokine involved in various immune responses, inflammation, and hematopoiesis. In the provided context, it's part of the signaling pathways that modulate immune responses. - -2. **Role in Pathways**: - - IL-6 interacts with its receptor, IL-6R, and the soluble form sIL-6Rα, to initiate signaling cascades involving pathways such as the JAK/STAT pathway (notably STAT3 phosphorylation). This can lead to the transcription of various genes, impacting inflammation and other immune responses. - - The mentioned pathways are part of a model studying IL-6 mediated immune regulation in diseases like Crohn’s disease, emphasizing IL-6's role in immune modulation. - -3. **Interactions with Other Molecules**: - - IL-6 typically binds to its receptor IL-6R or its soluble form sIL-6Rα. This complex can further interact with a signaling receptor gp130 to trigger downstream signaling events. - - In therapeutic contexts, antibodies targeting IL-6 or IL-6Rα, such as tocilizumab, interrupt these interactions to modulate immune responses, particularly in inflammatory diseases. - -4. **Importance in the Biological System Being Modeled**: - - The provided context describes a model exploring IL-6/sIL-6Rα interactions, and their targeting implications for modulating immune responses in inflammatory conditions. - - The simulations suggest that targeting both IL-6 and the IL-6/sIL-6Rα complex can potentially enhance therapeutic outcomes, highlighting the importance of these interactions in therapeutic strategies. - -Therefore, if 'Ab_sR_IL6' is related to IL-6/IL-6R interactions, it might be an antibody or related agent involved in modulating these interactions, potentially playing a role in therapeutic interventions for diseases involving IL-6 dysregulation." -mwbc2f5464_81e5_43fd_8b39_f5a2756af72f,"Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)",Ab,mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87,"The provided context does not explicitly mention specific background information or direct details about the species or molecule named 'Ab (mw8fbcbf3b_47d8_4adc_8ad4_f9fc547d3e87, #4)'. However, based on the surrounding context and general biological knowledge, some inferences can be made: - -### Inferred Background Information: -1. **Biological Function:** - - The abbreviation 'Ab' typically refers to an antibody. Antibodies are proteins that play crucial roles in the immune system by identifying and neutralizing foreign objects such as bacteria and viruses. - -2. **Role in Pathways:** - - Given the context mentioning IL-6 and IL-6Rα, it is likely that this antibody might be involved in the immune response pathway, possibly targeting components like interleukin-6 (IL-6) or its receptor. This suggests its participation in pathways that modulate inflammation or immune signaling. - -3. **Interactions with Other Molecules:** - - The context suggests interaction or targeting of the IL-6 or IL-6 receptor (IL-6Rα), indicating that this antibody might bind to these molecules, influencing inflammatory processes or immune responses. - -4. **Importance in the Biological System Being Modeled:** - - The system described seems to focus on understanding therapeutic strategies and modeling responses, possibly related to inflammatory diseases like inflammatory bowel diseases (IBDs) or conditions involving cytokines like IL-6. The antibody may be important for modulating these responses as part of a treatment strategy or for experimental observation. - -### General Inference: -- In systems biology, antibodies such as the one referred to, are often used experimentally or therapeutically to modulate biological pathways for research or treatment, particularly in immune response pathways dealing with cytokines. The context of IL-6 pathway targeting implies its significance in diseases managed by controlling inflammation, such as autoimmune or chronic inflammatory diseases. - -This inferred summary is based on typical roles and interactions of antibodies in biological research and therapeutic contexts, especially within the immune signaling pathways referenced in the context." diff --git a/notebook/species_backgrounds_final.csv b/notebook/species_backgrounds_final.csv new file mode 100644 index 00000000..1f62cf51 --- /dev/null +++ b/notebook/species_backgrounds_final.csv @@ -0,0 +1,751 @@ +id,name,original_name,compartment,background +mwf626e95e_543f_41e4_aad4_c6bf60ab345b,IL6{serum},IL6,serum,"Interleukin 6 (IL-6) is a cytokine with significant roles in the immune response, inflammation, and hematopoiesis. In the serum compartment, IL-6 acts as a key signaling molecule that can influence many biological functions and pathways. + +**Biological Function in Serum:** +IL-6 in serum is responsible for initiating and regulating the acute phase response during inflammation. It stimulates the production of acute-phase proteins such as C-reactive protein (CRP) by the liver, which helps in systemic inflammatory responses. IL-6's presence in serum is critical for mediating the communication between immune cells and influencing the adaptive immune system. + +**Role in Serum-specific Pathways:** +In the serum, IL-6 is involved in pathways related to the inflammatory response and cytokine signaling. It plays a central role in the cytokine release involved in inflammation, injury, and infection processes. IL-6 can activate various signaling pathways such as the JAK/STAT pathway that is crucial for transmitting signals from the cell surface to the DNA in the cell nucleus, ultimately affecting gene expression related to immune responses. + +**Interactions with Other Molecules in Serum:** +IL-6 interacts with soluble interleukin-6 receptor (sIL-6R) and glycoprotein 130 (gp130) to form a complex that can activate cells that do not naturally express the membrane-bound receptor for IL-6. This ""trans-signaling"" mechanism broadens the range of cells that can respond to IL-6. Additionally, IL-6 is a target of therapeutic antibodies like tocilizumab, which can attenuate its inflammatory effects by blocking IL-6 signaling pathways. + +**Importance of Serum Location for IL-6:** +The serum is an essential compartment for IL-6 as it facilitates the distribution of this cytokine throughout the body, allowing it to exert its effects on distal organs, particularly the liver, for the production of acute-phase proteins. The concentration of IL-6 in serum can also serve as a biomarker for various inflammatory and autoimmune conditions, reflecting the systemic inflammatory status of an individual. + +In summary, IL-6 in serum plays a vital role in mediating systemic inflammation and immune responses, participating in complex signaling networks, and interacting with other molecules to exert its effects across different tissues and organs." +mwbbbce920_e8dd_4320_9386_fc94bfb2fc99,sgp130{serum},sgp130,serum,"The provided documents do not offer explicit information specifically about sgp130 in the serum compartment (ID: mwbbbce920_e8dd_4320_9386_fc94bfb2fc99). However, based on general knowledge about sgp130 (soluble glycoprotein 130) and its relevance in serum, the following points can be inferred: + +1. **Biological Function in Serum:** + - sgp130 serves as a natural inhibitor of the interleukin-6 (IL-6) trans-signaling pathway in serum. It achieves this by binding to the IL-6/sIL-6Rα complexes, thereby preventing them from interacting with membrane-bound gp130 on cells and initiating signal transduction. + +2. **Role in Serum Pathways:** + - The primary role of sgp130 in serum is to modulate inflammatory responses. By specifically inhibiting IL-6 trans-signaling, sgp130 can help regulate processes such as immune response, inflammation, and acute phase reactions, which are crucial in various physiological and pathological conditions. + +3. **Interactions with Other Molecules:** + - sgp130 interacts with the IL-6/sIL-6Rα complex. It competitively prevents this complex from binding to cell surface gp130, thereby acting as a decoy receptor. + - The high baseline levels of sgp130 in serum compared to IL-6 suggest that the binding of sgp130 to the complex is a significant regulatory mechanism under normal physiological conditions. + +4. **Importance of Serum Location:** + - The presence of sgp130 in serum is crucial for maintaining homeostasis of the inflammatory response. Its ability to circulate allows it to systemically modulate IL-6 activity, thereby preventing excessive inflammatory signaling which could lead to chronic inflammation or autoimmune disorders. + +5. **Therapeutic Implications:** + - In therapeutic contexts, the use of sgp130Fc (a fusion protein combining sgp130 with an Fc region of an antibody) has been explored to enhance its inhibitory effects on IL-6 trans-signaling. In conditions like Crohn’s disease, high doses of sgp130Fc are needed for observable therapeutic effects, likely due to its role in modulating systemic inflammation. + +In summary, sgp130 in serum functions primarily as a modulator of IL-6-mediated inflammatory responses, providing regulatory control over signaling that could otherwise lead to pathological inflammation. Its significance in the serum lies in its systemic availability to modulate these responses effectively." +mw810ff751_fa4e_4143_bd50_169b3e325e1e,sR_IL6_sgp130{serum},sR_IL6_sgp130,serum,"Based on the provided context and general knowledge of similar biological components, the species named 'sR_IL6_sgp130{serum}' likely refers to the complex formed between soluble interleukin-6 receptor (sIL-6R), interleukin-6 (IL-6), and soluble glycoprotein 130 (sgp130) present in the serum compartment. + +1. **Biological Function in Serum:** + - The sgp130 protein serves as a natural inhibitor of IL-6 trans-signaling. In the serum, it binds to the IL-6/sIL-6R complex, thereby preventing this complex from engaging membrane-bound gp130 on cells. This inhibition modulates the inflammatory responses mediated by IL-6 trans-signaling pathways. + +2. **Role in Pathways Specific to Serum:** + - The IL-6/sIL-6R/sgp130 complex is involved in controlling inflammatory processes. By inhibiting IL-6 trans-signaling, sgp130 reduces the downstream activation of signal transducer and activator of transcription 3 (STAT3), which is crucial in several inflammatory and immune responses. + +3. **Interactions with Other Molecules in Serum:** + - The sgp130 interacts primarily with the IL-6/sIL-6R complex. The high baseline level of sgp130 in serum suggests it is in large excess compared to the low concentration of free IL-6, which limits the formation of the IL-6/sIL-6R complex. This ensures that sgp130 effectively inhibits IL-6-mediated signaling at typical physiological concentrations. + - sR_IL6_sgp130 may also have implications in serum protein, such as C-reactive protein (CRP) responses, which are indicators of inflammation. + +4. **Importance of Serum Location:** + - Serum is a key compartment where IL-6 signaling can exert systemic effects. The presence of sgp130 in serum is crucial as it provides check and balance for IL-6 signaling, maintaining homeostasis and preventing excessive inflammatory responses. + - The serum location permits the sgp130 to effectively intercept circulating IL-6/sIL-6R complexes before they can interact with cell surfaces, modulating widespread inflammatory responses. + +Overall, the primary role of sR_IL6_sgp130{serum} in the serum compartment is to regulate the activity of IL-6 by inhibiting its ability to signal through its soluble receptor, thus modulating inflammation and immune responses in the body." +mw114aa90f_5f5b_4fe8_9406_361c8489b6a1,CRP{serum},CRP,serum,"C-reactive protein (CRP) is an acute-phase protein predominantly found in the serum, where it is primarily produced by the liver in response to inflammation. Its biological function in the serum involves acting as a marker of inflammation, with its levels increasing significantly in response to inflammatory stimuli. This reaction typically occurs as a result of cytokine signaling, particularly through interleukin-6 (IL-6), which enhances CRP production as part of the body's systemic response to infection, injury, or other inflammatory conditions. + +In terms of its role in pathways specific to serum, CRP is part of the acute phase response, which involves the rapid increase or decrease of specific proteins in reaction to inflammation or infection. CRP operates as an opsonin, marking pathogens and dying cells for elimination by binding to phosphocholine on their surface and helping activate the complement system. This process facilitates phagocytosis by immune cells and contributes to the clearance of cellular debris and pathogens. + +CRP interacts with several other molecules in the serum. It is closely associated with IL-6's signaling pathway, as mentioned, which triggers its production. It can bind to ligands such as phosphocholine, initiating complement activation and enhancing phagocytosis. Additionally, CRP interacts with immune system components like complement protein C1q, augmenting the classical complement pathway, which is vital for immune defense. + +The serum location for CRP is crucial because it serves as a systemic marker for inflammation, providing a readily accessible metric for diagnosing and monitoring inflammatory diseases, infections, and tissue damage. Its presence in circulation allows it to rapidly respond to acute inflammatory signals, facilitating its role in immune surveillance and response initiation. + +In conclusion, CRP in serum functions as a critical inflammatory marker and immune system activator. Its levels provide clinical insights into the inflammatory status of an organism, assisting in the diagnosis and management of various conditions. The serum compartment is integral to its function due to the widespread availability and rapid response capability this location affords." +mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc,sR{serum},sR,serum,"The context provided from the document does not specifically mention a species named 'sR{serum}' in the serum compartment. However, the document does mention several other molecules and components in the serum, such as IL-6, sIL-6R, sgp130, and CRP, along with their roles and interactions. + +To infer based on general knowledge about similar biological components: + +1. **Biological Function in Serum**: Components in serum, often referred to by abbreviations like sIL-6R or sgp130, typically play roles in immune response regulation. For instance, soluble receptors like sIL-6R can modify cytokine activity, such as interleukin-6 (IL-6), by binding and transporting them to target cells, impacting inflammation and immune responses. + +2. **Role in Pathways Specific to Serum**: Soluble receptors in serum often interact with cytokines, mediating pathways that control inflammation, immune response, and cellular communication. These interactions are crucial in modulating conditions by affecting cytokine availability and activity. + +3. **Interactions with Other Molecules in Serum**: Molecules like sIL-6R interact with IL-6 to form complexes that can bind to receptors on cell surfaces, modifying the signaling pathway that typically involves the cytokine and its receptor. This interaction is vital for processes related to immune regulation and response. + +4. **Importance of Serum Location**: The serum compartment is important for such species as it acts as a conduit for transportation and interaction of signaling molecules, enabling the widespread distribution of soluble receptors and cytokines throughout the body. The presence in serum allows for quick systemic effects, crucial for immune surveillance and response. + +Given this, 'sR{serum}' might refer to a soluble receptor or similar molecule known for altering the activity of cytokines or other bioactive molecules in the serum, facilitating regulation of physiological or immune responses." +mw03db56ac_8dc6_4931_ae82_fef706d2ee3d,sR_IL6{serum},sR_IL6,serum,"Based on the provided context, there is no specific mention of a biological species or molecule named 'sR_IL6{serum}'. However, the context does provide information about related components like sIL-6R (soluble Interleukin-6 receptor), IL-6 (Interleukin-6), and their interactions in serum, which allows us to infer relevant background information. + +### Biological Function in Serum +IL-6 is a cytokine that plays a crucial role in the immune response, inflammation, and hematopoiesis. In serum, its biological activities are often mediated through its interaction with its receptor complex, which includes the membrane-bound receptor (IL-6R) and soluble forms (sIL-6R). + +### Role in Pathways Specific to Serum +IL-6 can signal through two main pathways: classical signaling and trans-signaling. Classical signaling occurs when IL-6 binds to the membrane-bound IL-6R, leading to the recruitment of gp130 and initiation of downstream signaling. Trans-signaling, on the other hand, involves the binding of IL-6 to sIL-6R in the serum, allowing the complex to interact with gp130 on cells that do not express IL-6R, thereby expanding the range of IL-6 effects. + +### Interactions with Other Molecules in Serum +The soluble Interleukin-6 receptor (sIL-6R) in serum can interact with IL-6 to form a complex, which is crucial in trans-signaling. This complex can subsequently associate with another protein, sgp130, which can act as a buffer to modulate the activity of the IL-6/sIL-6R complex. Pharmacological targeting of these molecules, as indicated by the effects of anti-IL-6Rα antibodies, can lead to changes in serum CRP levels, a marker of inflammation. + +### Importance of Serum Location for this Species +The presence of sIL-6R in serum is critical for IL-6 trans-signaling, allowing the cytokine to exert effects on a broader range of cells, including those that do not have the membrane-bound IL-6R. This mechanism enables systemic responses to inflammation and is a target for therapeutic interventions aimed at modulating immune responses. + +In summary, although there is no direct information about 'sR_IL6{serum}', the soluble Interleukin-6 receptor (sIL-6R) in serum plays a pivotal role in mediating the effects of IL-6 through trans-signaling pathways. This mechanism allows IL-6 to have systemic effects beyond cells expressing the membrane-bound receptor, influencing inflammation and immune response throughout the body." +mwf345ed7a_0622_403c_b816_c8749a2c9ded,Ab{serum},Ab,serum,"Based on the provided context and familiar principles of systems biology, I can infer some potential information about a species titled ""Ab{serum}"" in the serum compartment. However, there seems to be no specific reference to ""Ab{serum}"" in the provided excerpts, so I'll make educated assumptions based on general knowledge of antibodies in serum. + +### Biological Function in Serum +Antibodies (Ab) in serum typically serve the role of identifying and neutralizing foreign objects such as bacteria and viruses. They are crucial components of the immune system, allowing for the recognition of antigens and aiding in their destruction or neutralization. + +### Role in Serum-Specific Pathways +In the serum, antibodies participate in pathways such as the complement system, which helps to clear pathogens from an organism, and antibody-dependent cellular cytotoxicity (ADCC), which plays a role in the destruction of infected cells. They may also be involved in modulating inflammatory responses by interacting with receptors and signaling molecules in serum. + +### Interactions with Other Molecules +Antibodies in serum interact with a variety of other molecules, including antigens, components of the complement system, and various cell surface receptors. This can include binding to free antigens or those presented on cell surfaces, forming immune complexes that can be recognized and taken up by immune cells like macrophages. + +### Importance of Serum Location +The presence of antibodies in serum is vital as it allows them to circulate throughout the body, providing a systemic defense mechanism against pathogens. The serum compartment acts as a reservoir where these molecules can be rapidly distributed to infection sites, playing a crucial role in both recognition and effector phases of the immune response. + +Given the general behavior of antibodies and related molecules in serum, it's plausible that ""Ab{serum}"" refers to an antibody or antibody-like molecule playing a similar role in immune surveillance or a specialized immune response in the serum compartment. If ""Ab{serum}"" is something unique or specific to a particular study, it could similarly be an engineered or study-specific antibody variant used for research purposes, possibly to highlight changes in serum concentrations in response to a stimulus or drug treatment, as hinted at by the metrics of serum concentrations and interactions displayed in the provided context." +mw1da111f2_a036_4392_8512_015005bdcbb7,Ab_sR{serum},Ab_sR,serum,"The document context provided does not explicitly mention a species or molecule labeled 'Ab_sR{serum}' within the serum compartment. Therefore, I can infer its possible role based on general knowledge of similar biological components that are typically found in serum. + +1. **Biological Function in Serum:** + - If 'Ab_sR{serum}' is analogous to an antibody or receptor in the serum, it would be crucial in immune function. Antibodies in serum typically identify and neutralize pathogens such as bacteria and viruses. + +2. **Role in Pathways Specific to Serum:** + - In the context provided, antibodies (such as anti–IL-6 or anti–IL-6Rα) target specific cytokines and receptors, participating in pathways that modulate immune responses and inflammation. Thus, 'Ab_sR{serum}' could be involved in similar pathways where antibodies interact with cytokine receptors to regulate inflammatory responses. + +3. **Interactions with Other Molecules in Serum:** + - Again, assuming 'Ab_sR{serum}' is similar to antibodies, it might interact with antigens (like pathogens or proteins such as cytokines) or immune complexes in the serum. These interactions could influence the pathway outcomes, such as the suppression or promotion of inflammatory markers like C-reactive protein (CRP). + +4. **Importance of Serum Location:** + - Serum is the component of blood that remains after coagulation and is rich in proteins, including antibodies. The location allows for the circulation of antibodies throughout the body to quickly respond to potential threats. If 'Ab_sR{serum}' functions as an antibody, its presence in serum is vital for systemic immunity, allowing it to access and neutralize pathogens or regulate signaling pathways throughout the body. + +In summary, while specific details on 'Ab_sR{serum}' in the context are not provided, interpreting from general immune functions of serum components, it likely plays a role in pathogen neutralization and inflammation regulation within the circulatory system." +mw9947742a_0e4b_4636_9a4b_b6eef2a8f6ac,Ab_sR_IL6{serum},Ab_sR_IL6,serum,"The specific species 'Ab_sR_IL6{serum}' does not seem to be directly mentioned in the provided context. However, I can provide inferred background information based on the related biological components noted in the context and general knowledge. + +1. **Biological Function in Serum**: Inferred from similar entities such as IL-6/sIL-6R complex, antibodies against IL-6 (like anti–IL-6Rα), and the role of interleukin-6 (IL-6) in serum, it is likely that 'Ab_sR_IL6{serum}' functions as an antibody targeting IL-6 or its receptor complex in serum. Such antibodies usually work to modulate immune responses, reduce inflammation, and alter signaling processes that IL-6 is involved in, particularly in inflammatory diseases. + +2. **Role in Pathways Specific to Serum**: IL-6 is a cytokine involved in the immune response, inflammation, and hematopoiesis. In the serum, antibodies targeting IL-6 or its soluble receptor play roles in pathways that involve modulation of inflammation and immune system regulation. The context mentions the reduction of serum C-reactive protein (CRP), a marker of inflammation, which suggests this antibody's role in anti-inflammatory pathways by disrupting IL-6 mediated signaling. + +3. **Interactions with Other Molecules in Serum**: Based on the context, antibodies targeting IL-6 and its receptor would interact primarily with the IL-6/sIL-6R complex, IL-6 itself, or sIL-6R. They might inhibit the binding of IL-6 to its receptor, reducing downstream signaling and inflammatory responses. The presence of other molecules like sgp130, which can modulate IL-6 signaling, indicates potential interactions and broader network modulation within serum. + +4. **Importance of Serum Location**: Serum is a crucial compartment for immune signaling due to its role in transporting cytokines, antibodies, and signaling molecules throughout the body. The location of 'Ab_sR_IL6{serum}' in serum is vital as it allows for systemic modulation of IL-6 signaling, affecting both local and distant sites of inflammation and immune response. This is particularly important for therapeutic interventions aimed at managing systemic inflammatory conditions. + +In summary, while 'Ab_sR_IL6{serum}' isn't directly cited in the context, it likely functions as an antibody targeting IL-6 pathways in serum, integral in modulating inflammation and immune responses." +CRP_Suppression___,CRP Suppression (%){serum},CRP Suppression (%),serum,"Based on the provided context, there is limited specific information directly referring to a species named ""CRP Suppression (%){serum}"". However, the context does provide some relevant details about related mechanisms. + +### General Understanding of CRP Suppression in Serum: +1. **C-Reactive Protein (CRP)**: + - **Biological Function**: CRP is a critical acute-phase protein found in the serum, which increases in response to inflammation. + - **Serum Functionality**: It is a major component measured to assess levels of inflammation and is often used to monitor inflammatory diseases. + +2. **Role in Pathways Specific to Serum**: + - **Inflammatory Pathways**: CRP plays a role in the body's inflammatory response. In serum, its levels can change due to various factors, including infections and chronic inflammatory conditions. + +3. **Interactions with Other Molecules in Serum**: + - **Cytokine Interactions**: The context mentions interactions involving interleukin-6 (IL-6), a pro-inflammatory cytokine. IL-6 stimulates the production of CRP in the liver, affecting its serum levels. + - **Pharmacological Interventions**: The suppression of CRP levels in the serum is noted as a result of anti-IL-6 and anti-IL-6R antibody treatments. These treatments aim to reduce inflammation and CRP levels by blocking the IL-6 signaling pathway. + +4. **Importance of Serum Location for CRP**: + - **Diagnostic Marker**: Serum is the primary compartment where CRP levels are measured clinically. Its concentration in serum serves as a marker of inflammation and response to therapies. + +### Inferred Details Regarding ""CRP Suppression"" in Serum: +- ""CRP Suppression (%)"" likely refers to the reduction in CRP levels due to therapeutic interventions, especially those targeting the IL-6/IL-6R axis. +- The context indicates varying effectiveness of treatments (e.g., sgp130Fc, anti-IL-6, and anti-IL-6R antibodies) in modifying CRP levels in the serum. +- The reported suppression percentage would relate to assessing the efficacy of these interventions. + +### Summary: +Although ""CRP Suppression (%){serum}"" does not directly correspond to a unique species, it represents a measure of how effective modulation of systemic inflammation is achieved through pharmaceutical targeting of the IL-6 pathway in the serum compartment. CRP levels in serum are used as critical biomarkers to understand and monitor inflammation-related processes and the effectiveness of anti-inflammatory treatments." +CRP____of_baseline,CRP (% of baseline){serum},CRP (% of baseline),serum,"C-reactive protein (CRP) is an important biomarker and plays several critical roles when present in the serum compartment. Here is a summary of its biological function, role in pathways, interactions, and the significance of its serum location, based on the context and general knowledge: + +1. **Biological Function in Serum**: CRP is an acute-phase protein, predominantly produced by the liver in response to inflammation. Its levels in serum rise significantly during acute inflammatory responses, making it a reliable marker for gauging the presence and severity of inflammation. The measurement in the serum as a percentage of baseline is a method to assess changes relative to a standardized starting point. + +2. **Role in Serum Pathways**: In the serum, CRP is involved in the body's immune response to injury and infection. It enhances opsonization, which promotes the clearance of pathogens and damaged cells by macrophages. It plays a role in the classical complement pathway, which is crucial for immune system signaling and response amplification. + +3. **Interactions with Other Molecules in Serum**: CRP interacts with multiple other molecules in the serum. It binds to phosphocholine on the surface of dead or dying cells and some types of bacteria, facilitating their clearance. Additionally, it interacts with components of the complement system, such as C1q, to promote phagocytosis. CRP levels are regulated by cytokines such as interleukin-6 (IL-6), which is referenced in the context regarding treatments impacting IL-6 pathways. + +4. **Importance of Serum Location for CRP**: The serum location is critical for CRP because it allows for widespread distribution through the bloodstream, enabling it to efficiently reach sites of inflammation or injury. The serum-based measurement of CRP provides vital clinical information, serving as a diagnostic and prognostic tool for various inflammatory conditions. + +In conclusion, CRP (% of baseline) in serum is a fundamental indicator of inflammation, playing integral roles in immune response pathways and interacting with other serum components to effectuate its functions." +mw80848184_e2dd_47ce_86d7_7a21479342bd,gp130{liver},gp130,liver,"Based on the provided context and general knowledge about the molecule gp130, here is a summary of relevant information about gp130 in the liver compartment: + +**Biological Function in the Liver:** +- Gp130 is a transmembrane protein that serves as a signal transducer for a variety of cytokines, including interleukin-6 (IL-6). It is involved in transmitting the IL-6 signal inside the cell, which plays a crucial role in liver functions, such as mediating acute-phase responses, immune regulation, and liver regeneration. + +**Role in Liver-Specific Pathways:** +- In the liver, gp130 is particularly significant in the IL-6 signaling pathway. IL-6 binds to its specific receptor (IL-6R), which can either be membrane-bound or in a soluble form. The IL-6/IL-6R complex then associates with gp130 to initiate intracellular signaling cascades via the phosphorylation of the STAT3 protein. +- This signaling is crucial for the liver’s response to inflammation, stress, and injury, promoting hepatocyte survival and proliferation. + +**Interactions with Other Molecules in Liver:** +- Gp130 interacts with the IL-6/IL-6R complex to mediate signaling. +- It is also involved in complex formation with other cytokine receptors and coreceptors, which are essential for signal transduction. +- The soluble form of gp130 (sgp130) can act as an antagonist by binding to soluble IL-6/IL-6R complexes, thereby modulating the signaling intensity and preventing overactivation of the pathway, which is significant in regulating liver inflammation. + +**Importance of Liver Location:** +- The liver is a central organ in managing acute-phase responses and systemic inflammation, making the role of gp130 critical. In liver tissue, regulation of IL-6 signaling through gp130 is essential for controlling inflammation and maintaining homeostasis. +- Gp130’s expression and function in hepatocytes highlight its importance in liver-specific pathophysiological conditions, such as liver injury and repair processes. + +Though the provided context does not specify gp130’s interactions and functions exclusively in the liver, these inferred roles align with the known functions of gp130 and IL-6 signaling pathways in hepatic tissue." +mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a,R_IL6_gp130{liver},R_IL6_gp130,liver,"The species referred to as 'R_IL6_gp130{liver}' appears to be an interaction complex involving the interleukin-6 receptor (IL-6R), gp130 (the common signal transducer), and the cytokine interleukin-6 (IL-6) in the liver compartment. Although there is no specific mention of 'R_IL6_gp130{liver}' in the provided context, we can infer its potential roles based on the general understanding of IL-6 signaling in the liver: + +1. **Biological Function in Liver:** + - The IL-6/gp130 signaling pathway plays a critical role in the liver by mediating acute-phase responses. This involves the production of acute-phase proteins like C-reactive protein (CRP) that are crucial during inflammation and immune responses. + +2. **Role in Liver-specific Pathways:** + - IL-6 signaling through gp130 leads to the activation of signal transducer and activator of transcription 3 (STAT3), which is vital in the transcription of genes involved in inflammation, cell survival, and proliferation. In the liver, this pathway helps in regeneration and repair after injury. + +3. **Interactions with Other Molecules in the Liver:** + - The gp130 component is a common receptor subunit used by several cytokines, highlighting its broad significance in various signaling pathways. It forms complexes with IL-6 bound to its receptor (IL-6R) to initiate downstream signaling. + - The soluble form of gp130 (sgp130) can act as a natural inhibitor by sequestering the IL-6/IL-6R complex, preventing excessive signaling that could lead to uncontrolled inflammation. + +4. **Importance of Liver Location:** + - The liver is a primary site for the synthesis of serum proteins, including many acute-phase reactants, making it a crucial location for IL-6 signaling. The high expression of gp130 in hepatocytes underscores its significance in mediating IL-6-driven responses in the liver. + +The interaction between IL-6, its receptor, and gp130 is essential for proper liver function, particularly during immune challenges, underscoring the importance of the liver compartment for this signaling species." +mw4638f126_8cb8_4021_ab41_6ae195743ba0,sR_IL6{liver},sR_IL6,liver,"The species referred to as 'sR_IL6{liver}' in the context of the liver is likely a soluble form of the Interleukin-6 receptor (sIL-6R), based on general knowledge about similar biological components. + +### Biological Function in Liver: +- **sIL-6R in the liver** functions as a mediator of IL-6 signaling pathways. Soluble IL-6 receptors can bind to circulating IL-6, forming a complex that can interact with gp130, another receptor component. This interaction triggers intracellular signaling cascades involved in inflammation and immune responses. + +### Role in Liver-Specific Pathways: +- **IL-6 Signaling**: Both classical and trans-signaling pathways are relevant, with IL-6 signaling playing a critical role in liver inflammation and acute-phase protein synthesis. The soluble receptor facilitates trans-signaling, allowing cells that do not express the membrane-bound IL-6R to respond to IL-6. +- **C-Reactive Protein (CRP) Production**: IL-6 signaling via sIL-6R is associated with the induction of acute-phase proteins like CRP, a marker of inflammation commonly synthesized in the liver. + +### Interactions with Other Molecules: +- **IL-6**: The soluble receptor sIL-6R can form a complex with IL-6, enhancing its functional range by allowing cells lacking IL-6R to be activated by IL-6. +- **sgp130**: It acts as an antagonist to IL-6 trans-signaling by binding to the IL-6/sIL-6R complex, thereby neutralizing it and preventing excessive inflammatory signaling. +- **STAT3**: IL-6 signaling leads to the activation of STAT3 (Signal Transducer and Activator of Transcription 3), a major transcription factor that regulates genes involved in cell survival, proliferation, and inflammatory response. + +### Importance of Liver Location: +- **Central Role in Metabolism and Detoxification**: The liver is central to metabolic processes and detoxification, and its role in producing acute-phase proteins like CRP underscores the importance of IL-6 signaling in maintaining systemic and hepatic homeostasis. +- **Inflammation and Acute-Phase Response**: The liver's response to IL-6 through sIL-6R is crucial for orchestrating the systemic inflammatory response and synthesizing proteins that counteract inflammation and infection. + +Overall, sR_IL6's involvement in liver IL-6 signaling pathways suggests its significant role in mediating immune and inflammatory responses crucial for liver function and overall systemic health." +mw10315fa3_6f13_4618_bda8_a8694bd3c374,R{liver},R,liver,"The context provided does not include specific information about a species or molecule labeled ""R{liver}"" in the liver compartment with the specified ID. However, I can infer and provide relevant information based on general knowledge about common biological components found in the liver and their roles. + +### General Information about Common Species/molecules in the Liver: + +#### Interleukin-6 (IL-6) and Its Receptors in the Liver: + +1. **Biological Function in the Liver:** + - IL-6 is a cytokine that plays a significant role in immune responses. It is known to regulate acute-phase protein synthesis in the liver, such as C-reactive protein (CRP), which is mentioned in the context. + - The IL-6 signaling pathway in the liver involves the classical pathway and trans-signaling mechanisms. IL-6 binding leads to the activation of Signal Transducers and Activators of Transcription 3 (STAT3), which then translocates to the nucleus to mediate gene expression changes. + +2. **Role in Liver-Specific Pathways:** + - IL-6 is inherently involved in acute phase response pathways, crucial for the liver's reaction to inflammation and infection. + - The STAT3 signaling pathway is pivotal in hepatocytes for liver regeneration and repair. + +3. **Interactions with Other Molecules in the Liver:** + - In the context of liver function, IL-6 interacts with soluble IL-6 receptor (sIL-6R) and gp130, a signal transducing receptor component, which results in homodimerization and activation of intracellular signaling cascades. + - The liver exchanges these soluble components, such as CRP and other acute-phase reactants, into the bloodstream. + +4. **Importance of Liver Location:** + - The liver is a central organ in the systemic response to inflammation and is responsible for producing many proteins that mediate these effects. Its unique blood supply makes it an ideal site for the filtration and synthesis of these proteins. + +### Conclusion + +While specific details regarding ""R{liver}"" in the provided context are unavailable, the knowledge on IL-6 and associated signaling molecules provides an understanding of important cytokine functions in the liver compartment. These molecules are crucial for mediating the liver's response to systemic inflammation and regulating immune responses through pathways like those involving STAT3." +mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1,IL6{liver},IL6,liver,"The provided context discusses the role of IL-6 (Interleukin 6) in different tissues, with a focus on its involvement in signaling pathways associated with Crohn's disease. While the document does not provide detailed specific information about IL-6 function exclusively in the liver compartment, we can infer certain roles based on general knowledge of IL-6 and the available context. + +### Biological Function of IL-6 in the Liver: +IL-6 is a cytokine that plays a crucial role in the immune response and inflammation. In the liver, IL-6 is primarily involved in the acute-phase response, where it is responsible for inducing the production of acute-phase proteins such as C-reactive protein (CRP). The context mentions the liver's significant role in upregulating these proteins in diseases like Crohn's. + +### Role in Liver-Specific Pathways: +IL-6 signaling in the liver is central to initiating the Jak/STAT3 signaling pathway. This begins with IL-6 binding to its receptor IL-6Rα, which can be membrane-bound or soluble. The binding leads to the recruitment of the gp130 coreceptor, forming a receptor complex that activates Janus kinase (Jak) proteins. This subsequently leads to the phosphorylation of signal transducer and activator of transcription 3 (STAT3), culminating in the promotion of transcription of genes involved in the acute-phase response. + +### Interactions with Other Molecules in the Liver: +IL-6 forms a complex with its receptor that interacts with gp130, triggering intracellular signaling cascades. This interaction is crucial for the liver's response to systemic inflammation and the synthesis of proteins like CRP. The context suggests that the exchange of soluble components through blood serum is crucial for liver signaling dynamics. + +### Importance of Liver Location for IL-6: +The liver's role as a primary site for acute-phase protein production underscores the importance of IL-6 signaling in this organ. Its strategic location allows it to modulate systemic inflammation by producing proteins that circulate in the blood and affect other tissues. The liver's involvement in maintaining homeostasis during inflammatory responses highlights IL-6's significance in this location. + +In summary, while the specific document does not provide exclusive information on IL6 in the liver, we can deduce that IL-6 is vital in the liver for initiating and managing inflammatory responses, particularly through the production of acute-phase proteins via the Jak/STAT3 pathway. These processes underline the liver's essential function in response to systemic inflammation and diseases such as Crohn's." +mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83,R_IL6{liver},R_IL6,liver,"The provided documents mention several components related to interleukin-6 (IL-6) signaling, including soluble IL-6 receptor (sIL-6R) and the signaling regulator sgp130, within the contexts of different tissues, including the liver. However, they do not directly address the biological entity 'R_IL6{liver}' within the specified liver compartment. Based on general biological knowledge and the information provided, here is an inferred summary regarding the IL-6 receptor (R_IL6) and its significance in the liver: + +1. **Biological Function in Liver:** + - In the liver, the IL-6 receptor (R_IL6) participates in the signaling pathways initiated by IL-6, a key cytokine involved in immune responses, inflammation, and tissue regeneration. IL-6 binds to its receptor complex, which includes the membrane-bound IL-6 receptor (IL-6R) and the signal transducer glycoprotein 130 (gp130), leading to downstream signaling effects. + +2. **Role in Pathways Specific to Liver:** + - IL-6 is known to play a critical role in the acute-phase response in the liver, where it upregulates acute-phase proteins such as C-reactive protein (CRP). This response is part of the body's initial reaction to inflammation or infection, which can be mediated via both classical and trans-signaling pathways. + +3. **Interactions with Other Molecules in Liver:** + - In the liver, IL-6 interacts with soluble IL-6 receptor (sIL-6R) to facilitate trans-signaling alongside membrane-bound receptors. This interaction can modulate the effect of IL-6 on liver cells, allowing IL-6 to act on cells that do not express the membrane-bound IL-6R. + - sgp130 acts as an inhibitor of the IL-6/sIL-6R complex, moderating IL-6 signaling pathways by sequestering this complex, thus preventing excessive signaling. + +4. **Importance of Liver Location for this Species:** + - The liver serves as a crucial site for IL-6-mediated processes due to its central role in the systemic acute-phase response. The production of acute-phase reactants, triggered by IL-6 signaling, highlights the importance of IL-6 receptor activity in this organ. + - The liver's metabolic and detoxifying capabilities make it vital for modulating systemic cytokine levels and maintaining homeostasis during inflammation. + +In summary, although specific mention of 'R_IL6{liver}' is not made within the provided documents, the IL-6 receptor is integral to IL-6 signaling activities in the liver, influencing acute-phase protein production and immune responses." +mw0eb6c959_d408_45a0_a450_928b8c5876bb,Ractive{liver},Ractive,liver,"The context provided does not contain specific information about the species named 'Ractive{liver}' in the liver compartment (ID: mw0eb6c959_d408_45a0_a450_928b8c5876bb). Therefore, to infer its potential roles based on general knowledge about biological molecules in the liver, here's what can be considered: + +### Biological Function in Liver: +The liver is a central organ in metabolism and detoxification, managing various biochemical pathways. Molecules in the liver often have roles in processes such as the synthesis and breakdown of carbohydrates, lipids, and proteins, detoxification of substances, and the regulation of plasma protein levels such as albumin and acute-phase proteins. + +### Role in Liver-Specific Pathways: +- **Metabolic Pathways**: Many molecules in the liver are involved in metabolic pathways, including glycolysis, gluconeogenesis, fatty acid oxidation, and bile acid synthesis. +- **Acute-Phase Response**: The liver plays a crucial role in the acute-phase response, especially in diseases like Crohn’s disease, as mentioned in the context. This involves the production of acute-phase proteins such as C-reactive protein (CRP). + +### Interactions with Other Molecules: +The liver often interacts with circulating molecules such as cytokines (e.g., IL-6) and hormones that regulate metabolic processes. For instance, IL-6 is involved in the induction of acute-phase proteins in the liver. + +### Importance of Liver Location for this Species: +If 'Ractive{liver}' is an active component of signaling or metabolic pathways, its location in the liver suggests it may be involved in managing responses to systemic inflammation, metabolic regulation, or detoxification processes unique or specialized within liver tissues. + +### Inference: +Given the mention of IL-6 signaling and acute-phase proteins in the context, 'Ractive{liver}' could potentially be involved in similar pathways, perhaps as a component or regulator within these processes. + +Without more specific details in the context, understanding of 'Ractive{liver}' in the liver compartment is based on these generalized functions and interactions typical of liver-resident molecules." +mw42054cd7_17af_46da_970c_7f99151906ad,STAT3{liver},STAT3,liver,"Based on the provided context, the specific information regarding STAT3{liver} in the liver compartment is not detailed. However, I can infer and summarize potential roles and importance based on general knowledge about STAT3 and its involvement in the liver: + +### Biological Function in the Liver: +- **Signal Transduction**: STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that plays a crucial role in transmitting signals from the cell surface to the nucleus upon activation by various ligands such as cytokines. +- **Acute Phase Response**: In the liver, STAT3 is prominently involved in mediating the acute phase response, which is a rapid inflammatory response to tissue injury or infection, leading to the production of acute-phase proteins like C-reactive protein (CRP). + +### Role in Liver-Specific Pathways: +- **IL-6 Signaling Pathway**: STAT3 is a key component of the IL-6 signaling pathway, which is vital for liver inflammation and tissue regeneration. The context indicates that STAT3 is phosphorylated (pSTAT3) following IL-6 signaling, highlighting its activation. +- **Interaction with Soluble IL-6 Receptor (sIL-6R)**: The context suggests that the interaction of IL-6 with its soluble receptor (sIL-6R) can activate STAT3 in hepatocytes, emphasizing its role in the liver environment. + +### Interactions with Other Molecules in the Liver: +- **C-Reactive Protein (CRP)**: STAT3 is implicated in the upregulation of acute-phase proteins such as CRP, which further indicates its role in liver inflammation. +- **gp130**: The ubiquitously expressed co-receptor gp130 facilitates signaling pathways involving STAT3 when associated with IL-6 and sIL-6R. + +### Importance of Liver Location for STAT3: +- **Liver as a Central Node for Metabolic and Inflammatory Signaling**: STAT3’s presence and activity in the liver signifies its crucial role in coordinating metabolic and inflammatory processes. The liver serves as an integration hub for systemic inflammation and metabolic regulation, where STAT3 contributes significantly to both. + +Though specific interactions or pathways exclusive to the liver compartment are not detailed in the context, these inferred functions and interactions highlight the importance of STAT3 in maintaining liver function and responding to systemic inflammatory signals." +mw39c2e431_fdc3_4964_be29_6ca856620b1b,pSTAT3{liver},pSTAT3,liver,"The context provided does not contain specific information about pSTAT3 in the liver compartment. However, based on general knowledge about the role of phosphorylated STAT3 (pSTAT3) in the liver, we can infer its functions and importance as follows: + +1. **Biological Function in Liver**: + - pSTAT3 is a phosphorylated form of the STAT3 protein, a critical transcription factor involved in cell signaling pathways. In the liver, STAT3 becomes phosphorylated in response to cytokine signaling, particularly interleukin-6 (IL-6) signaling. + - It plays a pivotal role in the liver's acute phase response, where it regulates the expression of acute-phase proteins, which are essential for the immune response and inflammation regulation. + +2. **Role in Liver-Specific Pathways**: + - In the liver, pSTAT3 is crucial for mediating the effects of cytokines like IL-6, which is prominent during liver inflammation and regeneration processes. This signaling pathway can be vital in pathological conditions such as liver fibrosis, hepatitis, and liver cancer. + - It is also involved in glucose metabolism regulation and liver regeneration, hence contributing to systemic metabolic homeostasis. + +3. **Interactions with Other Molecules in Liver**: + - pSTAT3 interacts with various proteins and cofactors in the liver to modulate gene expression. It is activated by upstream Janus kinases (JAKs) that phosphorylate STAT3 upon cytokine receptor engagement. + - pSTAT3 is known to interact with suppressors of cytokine signaling (SOCS) proteins, which are part of a negative feedback loop to inhibit excessive cytokine signaling. + - Additionally, it can interact with other transcriptional regulators and co-activators to fine-tune gene expression required for hepatic responses. + +4. **Importance of Liver Location for this Species**: + - The liver is a major site of acute-phase protein synthesis, and pSTAT3 is a key regulator of this process. Its activity in the liver ensures a rapid and effective response to injury and infection. + - The hepatic environment provides a rich tapestry of cytokine signals essential for the activation of STAT3. The liver's strategic anatomical and functional position makes it an ideal site for STAT3-mediated modulation of systemic metabolic and immune responses. + +Overall, pSTAT3 in the liver is fundamental for translating extracellular cytokine signals into appropriate intrahepatic responses, with significant implications for liver physiology and pathology." +mwd5313618_89eb_4c8c_bc82_66f10f966349,CRP{liver},CRP,liver,"Based on the given context, there is no specific information about the species 'CRP{liver}' in the liver compartment (ID: mwd5313618_89eb_4c8c_bc82_66f10f966349). However, by extrapolating from general knowledge about C-reactive protein (CRP), we can infer its role and importance in the liver: + +1. **Biological Function in the Liver:** + - CRP is a well-known acute-phase protein that is primarily synthesized in the liver. + - Its production is primarily stimulated by pro-inflammatory cytokines, particularly interleukin-6 (IL-6). + +2. **Role in Liver-Specific Pathways:** + - In the context of inflammation or infection, CRP plays a crucial role in the systemic response by binding to phosphocholine on the surface of dead or dying cells and some bacteria, aiding in their clearance by macrophages (phagocytosis). + - In the liver, CRP contributes to processes like opsonization, complement activation, and modulation of the immune response. + +3. **Interactions with Other Molecules in the Liver:** + - CRP interacts with complement proteins, notably C1q, initiating the classical complement pathway. + - It may influence liver cells' interactions with cytokines and other immune-modulating proteins, such as IL-6, as suggested in the context of its modeling in response to anti-IL-6Rα antibody treatments. + +4. **Importance of Liver Location:** + - The liver is the primary site of CRP synthesis. Hepatocytes (liver cells) are responsible for its production following stimulation by systemic cytokines. + - This localization is crucial because the liver integrates multiple systemic signals to regulate the synthesis of acute-phase proteins, adjusting the body's inflammatory response. + +In summary, while specific information about 'CRP{liver}' in the document context is absent, CRP's general role as an acute-phase reactant synthesized in the liver allows us to deduce its critical function in inflammatory responses and systemic defense mechanisms." +mw2e464cf3_a09c_4b7c_9f3c_06720016a48e,sR{liver},sR,liver,"The provided context does not contain specific information about a species named 'sR{liver}' in the liver compartment. However, it mentions several related components involved in IL-6 signaling pathways, including sIL-6R (soluble interleukin-6 receptor), IL-6, sgp130, and CRP (C-reactive protein), which provide a basis to infer the role and function of similar molecules in the liver. + +### Inferred Background Information on sR{liver} in the Liver: + +1. **Biological Function in Liver**: + - Soluble cytokine receptors like sIL-6R are typically involved in modulating inflammatory responses and cytokine signaling. In the liver, they can influence processes such as the acute phase response and hepatic regeneration. + +2. **Role in Liver-Specific Pathways**: + - The IL-6/sIL-6R complex is involved in classical and trans-signaling pathways. In the liver, IL-6 is known to activate signaling pathways leading to the phosphorylation of STAT3 (pSTAT3), a transcription factor that modulates the expression of various genes, including those related to inflammation and metabolism. + +3. **Interactions with Other Molecules in Liver**: + - sIL-6R can form complexes with IL-6, which can further bind to sgp130, affecting signal transduction. + - CRP-mediated shedding is mentioned as a mechanism for sIL-6R production, indicating interactions between CRP and sIL-6R in the liver tissue. + +4. **Importance of Liver Location**: + - The liver is central to the synthesis of many acute-phase proteins and is involved in the systemic immune response. Compounds like sIL-6R play a critical role in liver-specific signaling pathways that influence systemic inflammation and metabolic processes. + +Given this information, if sR{liver} is analogous to known soluble receptors like sIL-6R, it would likely play a role in modulating signaling pathways in the liver involved in inflammation, metabolism, and systemic immune responses." +mw36ea78c1_ed71_4def_96d3_857a442d7195,CRPExtracellular{liver},CRPExtracellular,liver,"C-reactive protein (CRP) is an acute-phase protein predominantly synthesized and secreted by the liver. In the context of the liver, CRP serves several biological functions and plays a role in various pathways: + +1. **Biological Function in the Liver:** + - CRP is primarily produced by hepatocytes in response to pro-inflammatory cytokines, particularly interleukin-6 (IL-6). Its production is part of the liver's response to inflammation, infection, and tissue damage. + +2. **Role in Liver-Specific Pathways:** + - In liver-associated pathways, CRP plays a crucial role in the acute phase response, which is a rapid inflammatory response intended to restore homeostasis. This response includes the upregulation of acute-phase proteins, such as CRP, which act to limit damage, isolate infections, and promote healing. + - The production of CRP is part of the liver's role in mediating systemic inflammation and is often a marker for inflammatory diseases, including Crohn's disease as outlined in the provided context. + +3. **Interactions with Other Molecules in the Liver:** + - CRP interacts with components of the immune system, such as complement proteins, to help in pathogen recognition and clearance. + - It is involved in the modulation of the IL-6 signaling pathway. The context mentions the IL-6 signaling module in liver cells, which suggests that CRP is part of this signaling network. It leads to the shedding of soluble IL-6 receptors (sIL-6Rα) via CRP-mediated mechanisms, implying a role in inflammatory signal modulation. + +4. **Importance of the Liver Location:** + - The liver is a central organ for the synthesis of acute phase proteins, including CRP. This specific location allows for the rapid production and release of CRP into the bloodstream in response to systemic inflammation. + - The liver's unique role in metabolism and detoxification makes it an ideal site for regulating systemic inflammatory responses and the production of proteins like CRP. + +In summary, CRPExtracellular{liver} is a significant marker of inflammation synthesized in the liver, with critical roles in the acute phase response and inflammatory pathways influenced by the cytokine IL-6. Its interactions and regulation within the liver are vital for managing systemic inflammatory responses, illustrating its importance in this compartment." +mw147d30ec_478e_4090_b496_128a131d29eb,sgp130{liver},sgp130,liver,"The provided context does not specifically mention 'sgp130{liver}' within the liver compartment. However, based on the general information about sgp130 and its biological context, I can make some inferences regarding its function in the liver. + +### General Information about sgp130 and Inferences about its Role in the Liver: + +1. **Biological Function in Liver:** + - sgp130 is a soluble form of the coreceptor gp130, which acts as a natural inhibitor of IL-6 trans-signaling. It does so by sequestering the IL-6/sIL-6Rα complex, preventing the downstream signaling pathways that are generally associated with inflammation. + - In the liver, IL-6 signaling is crucial for the expression of acute-phase proteins, such as C-reactive protein (CRP). The inhibition of IL-6 trans-signaling by sgp130 could therefore modulate the liver's acute-phase response. + +2. **Role in Liver-Specific Pathways:** + - The liver is a key organ involved in the systemic inflammatory response, and IL-6 plays a central role in mediating this response. By inhibiting IL-6 trans-signaling, sgp130 could potentially impact acute-phase protein synthesis and other IL-6 induced pathways in the liver. + - This regulation might be important in pathological conditions where IL-6 driven inflammation needs to be controlled, such as in certain liver diseases or systemic inflammatory conditions. + +3. **Interactions with Other Molecules in the Liver:** + - No specific interactions of sgp130 within the liver compartment are detailed in the context. However, its role as an inhibitor of IL-6 trans-signaling implies interactions with IL-6, sIL-6Rα, and molecules involved in the downstream signaling cascade, such as STAT3. + - The presence of sgp130 in the liver could mitigate excessive IL-6 signaling and thus interact indirectly with other hepatic signaling pathways influenced by cytokines and acute-phase reactants. + +4. **Importance of Liver Location for This Species:** + - The liver is a critical site for the synthesis and systemic release of many proteins, including those involved in immune responses. The presence and regulation of sgp130 in the liver can be crucial for maintaining a balance in cytokine signaling and preventing excessive inflammation. + - Given the liver's role in detoxification and metabolism, sgp130 might also play a part in modulating the immune response to prevent collateral damage to liver tissues during inflammatory processes. + +Although explicit details about sgp130 specifically in the liver are lacking, its general function as an inhibitor of IL-6 cytokine trans-signaling is likely relevant to its hypothetical role within this tissue, particularly in relation to managing inflammation and the acute-phase response." +mwab41493c_6349_45f1_a226_3030cfed0e06,sR_IL6_sgp130{liver},sR_IL6_sgp130,liver,"The species 'sR_IL6_sgp130{liver}' likely represents a complex involving soluble IL-6 receptor components (sIL-6R) and the soluble form of the gp130 receptor (sgp130) within the liver compartment. Here's a summary of its potential roles and interactions based on the provided context and general knowledge: + +1. **Biological Function in the Liver:** + - In the liver, IL-6 signaling plays a crucial role in mediating inflammatory responses and the acute-phase reaction, which includes the induction of proteins such as C-reactive protein (CRP). The sIL-6R allows cells that do not normally express membrane-bound IL-6R to respond to IL-6 via a process known as trans-signaling. The soluble form of gp130 (sgp130) acts as a natural inhibitor of this trans-signaling pathway by sequestering the IL-6/sIL-6R complex, potentially modulating inflammatory responses. + +2. **Role in Liver-Specific Pathways:** + - IL-6 is pivotal in liver signaling pathways that are involved in the acute-phase response. Its interaction with the liver synthesizes and releases acute-phase proteins like CRP, which are indicators of inflammation and are clinically relevant for assessing inflammatory diseases and conditions. + +3. **Interactions with Other Molecules in the Liver:** + - The complex involving sIL-6R and sgp130 interacts with the IL-6 cytokine itself. In the liver, this interaction impacts the signaling pathways leading to STAT3 phosphorylation, which is crucial for mediating responses to inflammation and stress. + - The complex can modulate the availability of IL-6 for signaling by binding to it and preventing its interaction with cell-surface receptors, thus influencing the overall inflammatory response in the liver. + +4. **Importance of Liver Location for This Species:** + - The liver is a central organ for metabolism and immune response. Location in the liver means this complex plays a crucial role in mediating systemic inflammation and in the regulation of acute-phase proteins. The expression and activity of this complex in the liver help modulate the balance between necessary immune activation and prevention of excessive inflammatory responses. + +While the context does not provide direct quotes about 'sR_IL6_sgp130{liver}', these insights are inferred from general knowledge about IL-6 signaling pathways and the role of liver in immune responses." +mwf405687b_7401_44ec_a0d6_4a2b35c13e8a,Ab_sR{liver},Ab_sR,liver,"The provided context does not specifically mention a species or molecule named 'Ab_sR{liver}' in the liver compartment. However, we can provide insights based on general knowledge regarding molecules and pathways in the liver that might align with the general idea of an ""Ab"" (antibody) related species. + +1. **Biological Function in Liver:** + In the liver, antibodies or related molecules can be involved in immune responses. The liver is a key organ in the immune system and produces various proteins, including those necessary for the immune response such as complement proteins and acute-phase proteins like C-reactive protein (CRP). + +2. **Role in Pathways Specific to Liver:** + In the context of the liver, trans-signal pathways like the IL-6 signaling are essential. IL-6 is involved in liver inflammation and the acute-phase response. If 'Ab_sR' refers to an antibody-related species, it might be interacting with or modulating the immune signaling pathways like IL-6 signaling cascade in the liver. + +3. **Interactions with Other Molecules in Liver:** + In the liver, antibodies or soluble receptors might interact with acute-phase proteins such as CRP or pathways involving interleukins like IL-6, as seen in the context. These interactions could be crucial for modulating immune responses or inflammation within the liver. + +4. **Importance of Liver Location for this Species:** + The liver is a central metabolic and immune organ, processing and clearing various substances, including antigens and immune complexes, from circulation. The location is critical for immunological surveillance and the generation of a systemic immune response, which may include the regulation of antibodies or soluble receptors. + +Given these points, if 'Ab_sR{liver}' is a specialized antibody or receptor involved in immune modulation, its presence in the liver could imply a role in the systemic immune or acute-phase response, potentially interacting with key proteins and signaling pathways active in liver tissue." +mw3667a5e1_02c9_44a0_acb4_b0431faa822d,Ab{liver},Ab,liver,"Based on the provided context, there appears to be no direct mention or specific information regarding the biological species named 'Ab{liver}' in the liver compartment. However, I can provide some inferred information based on general knowledge about biological components referencing antibodies (Ab) and the liver's role in the immune response. + +### Inferred Background Information about Ab{liver} in the Liver: + +1. **Biological Function in Liver**: + - Antibodies, often denoted as ""Ab"", have roles in the immune response by identifying and neutralizing pathogens like bacteria and viruses. In the liver, antibodies could play a crucial role in preventing infections by clearing pathogens from the bloodstream and interstitial fluid, given the liver’s role in filtering blood. + +2. **Role in Liver Pathways**: + - The liver is a key organ involved in the acute-phase response, an aspect of the immune response that can be upregulated or modulated by antibodies through interactions with the innate immune system. The acute-phase response includes the production of proteins such as C-reactive protein (CRP), which is associated with inflammation and can indicate the presence of systemic inflammatory activity—potentially upregulated during liver involvement in systemic diseases like Crohn’s disease. + +3. **Interactions with Other Molecules in Liver**: + - In the context of Crohn’s disease, as mentioned in the document, the liver plays a significant role by interacting with cytokines such as IL-6. This cytokine is pivotal in liver signaling pathways that modulate inflammation and acute-phase protein production. Antibodies specific to cytokines (e.g., Anti-IL-6 antibodies) can directly interact with these signaling molecules to suppress inflammation. + +4. **Importance of Liver Location for this Species**: + - The liver's strategic location and its ability to filter blood make it a crucial site for antibody action, where systemic antibodies can exert their function by interfacing with liver macrophages (Kupffer cells) and hepatocytes involved in detoxification and metabolic regulation of immune responses. The liver is essential in maintaining immune homeostasis and processing immune complexes and antibodies generated during immune responses. + +In essence, while the specific 'Ab{liver}' is not described in the supplied context, antibodies in general play a crucial role in the liver by engaging with the immune system and being involved in inflammatory processes, particularly related to diseases that may have systemic effects, such as Crohn's disease." +mw772cbf20_3fc1_4800_ae59_77884f1ae333,Ab_R{liver},Ab_R,liver,"The context provided does not offer specific information about a species named 'Ab_R{liver}' in the liver compartment, identified by ID mw772cbf20_3fc1_4800_ae59_77884f1ae333. However, we can infer some details based on general knowledge about antibodies and their potential role in the liver. + +1. **Biological Function in Liver**: + Antibodies in the liver can play a significant role in immune response and detoxification processes. The liver is crucial for clearing pathogens and foreign substances from the blood, and antibodies can target specific antigens for clearance. + +2. **Role in Pathways Specific to Liver**: + In the context of the liver, antibodies often participate in pathways related to immune surveillance. They may be involved in pathways related to antigen processing and presentation, potentially interacting with liver cells such as Kupffer cells, which are specialized macrophages situated in the liver. + +3. **Interactions with Other Molecules in Liver**: + Antibodies, especially those targeting cytokines like IL-6 or its receptor (as discussed in the context), can modulate inflammatory responses by interacting with cytokine signaling molecules. They might bind to proteins such as IL-6R or influence downstream signaling pathways involving molecules like STAT3 and CRP. + +4. **Importance of Liver Location for This Species**: + The liver's strategic location and function as a blood filter make it a prime site for antibodies to act. It is involved in systemic immune surveillance and can rapidly respond to pathogens or foreign molecules by mounting an immune response. + +In this context, based on the information about treatments targeting IL-6 and sIL-6R, the presence of an antibody in the liver could suggest a role in modulating inflammatory responses or autoimmune processes, playing part in therapeutic strategies aimed at reducing inflammation or cytokine-mediated damage in diseases affecting the liver or systemic circulation." +mw2ba2b802_9f07_4f4d_94c6_24c8de1a95cf,Ab_sR_IL6{liver},Ab_sR_IL6,liver,"Based on the provided context and general scientific knowledge, here is a summary of the potential role and characteristics of 'Ab_sR_IL6{liver}' in the liver compartment: + +1. **Biological Function in Liver**: + - 'Ab_sR_IL6{liver}' seems to be related to sIL-6R (soluble interleukin-6 receptor), which is a molecule involved in IL-6 signaling pathways. The liver plays a significant role in the acute phase response, and IL-6 is a critical cytokine mediating these responses. + - In the liver, IL-6 can promote the expression of acute-phase proteins such as C-reactive protein (CRP) through activation of STAT3 (Signal Transducer and Activator of Transcription 3). + +2. **Role in Liver-Specific Pathways**: + - Within the liver, IL-6/sIL-6R complex can activate classical and trans-signaling pathways involving the JAK/STAT signaling cascade. This leads to the transcriptional activation of specific genes involved in inflammatory responses. + - The liver-specific pathway includes gene products like CRP, which are crucial during systemic inflammation and infection responses. + +3. **Interactions with Other Molecules in Liver**: + - The sIL-6R, part of the IL-6/sIL-6R complex, can interact with the signaling protein gp130, leading to downstream effects including STAT3 phosphorylation. + - The interactions involve binding of IL-6 to sIL-6R, forming a complex that engages with membrane-bound gp130, which is highly expressed in the liver. + +4. **Importance of Liver Location**: + - The liver is strategically important as both a source and a target of the acute-phase response modulated by IL-6 signaling. + - The production of sIL-6R is enhanced by the shedding process mediated by CRP, emphasizing the liver’s central role in such immune signaling networks. + +In summary, while specific details about 'Ab_sR_IL6{liver}' are limited, its components, namely sIL-6R and IL-6, are central figures in liver inflammation and immune response pathways. The liver's involvement in IL-6 mediated pathways underscores its function in systemic inflammatory regulation and acute-phase protein production." +mw7becb5fe_8da8_4285_a821_0d77ad811b62,sR_IL6{gut},sR_IL6,gut,"The species referred to as 'sR_IL6{gut}' likely pertains to the soluble IL-6 receptor (sIL-6R) within the gut compartment. Here's a summary of relevant background information, inferred from the given context and general knowledge about IL-6 signaling: + +1. **Biological Function in the Gut:** + - The soluble IL-6 receptor (sIL-6R) plays a role in the trans-signaling pathway of IL-6. This involves the soluble form of the receptor, which can bind to IL-6, allowing the complex to interact with gp130, a signal-transducing component expressed on the surfaces of most cells, thus initiating signaling cascades typically involved in inflammatory responses. + - In the gut, IL-6 signaling is particularly significant due to its implication in inflammatory processes, such as those seen in Crohn’s disease, where it contributes to enhanced T-cell survival and resistance to apoptosis, aiding in chronic inflammation. + +2. **Role in Gut-Specific Pathways:** + - Trans-signaling via sIL-6R in the gut is implicated in promoting pro-inflammatory responses that are characteristic of gut-associated diseases like inflammatory bowel disease (IBD). + - It can enhance the secretion of chemokines and other inflammatory mediators which exacerbate the inflammatory environment, playing a role in the pathology of diseases affecting the gastrointestinal tract. + +3. **Interactions with Other Molecules in the Gut:** + - The sIL-6R binds to IL-6 and the complex interacts with the membrane-bound gp130 receptor. This subsequently leads to the activation of Janus kinases (Jak) and the phosphorylation of STAT3, a transcription factor that modulates the expression of various genes involved in cell survival, proliferation, and differentiation. + - Such interactions are critical in amplifying inflammatory signals and can influence the behavior of immune cells within the gut. + +4. **Importance of Gut Location:** + - The presence of sIL-6R in the gut is important because this compartment typically has high immune activity and requires tight regulation of inflammation to maintain tissue homeostasis. + - The unique environment of the gut, with its diverse microbiota and continual exposure to dietary antigens and pathogens, makes the regulation of IL-6 signaling crucial for preventing excessive inflammation that can lead to tissue damage and diseases such as IBD. + +Overall, the sIL-6R in the gut plays a vital role in modulating immune responses and can significantly impact the pathophysiology of gut-associated inflammatory diseases." +mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca,gp130{gut},gp130,gut,"The context provided does not explicitly mention ""gp130{gut}"" in relation to its biological function, role in pathways, interactions, or specific importance within the gut compartment. However, based on general knowledge about gp130 and its known biological functions, we can infer its potential roles in the gut: + +1. **Biological Function in the Gut:** + - gp130 is a signal transducing receptor component for several cytokines, notably interleukin-6 (IL-6). In the gut, gp130 mediates IL-6 signaling, which is crucial for maintaining mucosal integrity and immune response. It can influence inflammation and mucosal protection, which are vital in conditions like inflammatory bowel disease (IBD). + +2. **Role in Gut-specific Pathways:** + - In the gut, gp130 is part of the IL-6 signaling pathway, which plays a role in inflammatory processes. IL-6 is known to be elevated in conditions such as Crohn’s disease. gp130 forms part of a receptor complex with IL-6 and its soluble receptor (sIL-6R), triggering downstream signaling that can lead to the activation of transcription factors like STAT3. + +3. **Interactions with Other Molecules:** + - gp130 interacts with IL-6 and the soluble IL-6 receptor (sIL-6R) to form a signaling complex. Soluble gp130 (sgp130) acts as a natural inhibitor of IL-6 trans-signaling by binding to the IL-6/sIL-6R complex, preventing it from associating with membrane-bound gp130 and thus inhibiting inflammatory signaling. + +4. **Importance of Gut Location:** + - The gut is a significant site for immune activity and inflammation regulation, making the presence and function of signaling molecules like gp130 critical. The ability of gp130 to mediate responses to IL-6 makes it essential for responding to gut-specific challenges, such as microbial encounters and inflammatory conditions that could compromise gut barrier function. + +Overall, while the specific species ""gp130{gut}"" is not directly described, the role of gp130 as a crucial component in cytokine signaling, particularly IL-6, suggests its significant impact on gut homeostasis and its potential implications in gut-related diseases." +mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9,R_IL6_gp130{gut},R_IL6_gp130,gut,"The context provided does not directly mention the specific species 'R_IL6_gp130{gut}', but general information about related molecules allows for the following inferences: + +1. **Biological Function in Gut:** + - 'R_IL6_gp130{gut}' likely refers to a receptor complex involving Interleukin-6 (IL-6) and its signaling components, such as the glycoprotein 130 (gp130). In the gut, IL-6 plays a critical role in immune response regulation and inflammation. It is particularly involved in the pathophysiology of inflammatory bowel diseases (IBD) such as Crohn's disease. + +2. **Role in Pathways Specific to Gut:** + - The IL-6 signaling pathway in the gut involves both classical and trans-signaling mechanisms. In classical signaling, IL-6 binds to its membrane-bound receptor and gp130, leading to the activation of intracellular signaling cascades such as the JAK/STAT pathway. In trans-signaling, a soluble form of the IL-6 receptor (sIL-6R) can bind IL-6, and this complex can then interact with membrane-bound gp130 on cells that do not express the IL-6 receptor. This pathway is significant in chronic inflammatory conditions affecting the gut. + +3. **Interactions with Other Molecules in Gut:** + - Interactions include binding of IL-6 to its receptor IL-6R, followed by the recruitment of gp130 to form a signaling complex. This complex can activate pathways that lead to the production of acute-phase proteins like C-reactive protein (CRP) and other inflammatory mediators. + - In the context of therapeutic approaches, soluble gp130 (sgp130) can inhibit IL-6 trans-signaling by binding the IL-6/sIL-6R complex, preventing its interaction with membrane-bound gp130. + +4. **Importance of Gut Location for this Species:** + - The gut is a primary site for immune regulation and is often involved in inflammatory responses. IL-6 and its signaling components play a significant role here by modulating local immune responses and maintaining epithelial homeostasis. Dysregulation of IL-6 signaling in the gut can contribute to diseases such as Crohn’s disease. + +In summary, while specific details about 'R_IL6_gp130{gut}' are not provided, the likely role of this complex in the gut involves participation in IL-6-mediated signaling pathways, which are crucial for immune regulation and inflammation control within the gastrointestinal tract." +mw6cce2109_0e32_4dd9_98ec_41173e8ef07d,Ractive{gut},Ractive,gut,"Based on the provided context, there is no specific mention of a species named 'Ractive{gut}' in the gut compartment or in relation to the gut. The context mainly discusses topics related to inflammatory bowel disease, IL-6 signaling, and systems pharmacology, with a focus on Crohn’s disease and rheumatoid arthritis, involving IL-6 and its receptor components. + +In the absence of specific information about 'Ractive{gut}' in the gut, we can infer what this might relate to based on general understanding of typical biological roles and interactions within the gut: + +1. **Biological Function in the Gut**: If 'Ractive{gut}' is a molecule or species related to gut biology, it might participate in the regulation of immune responses, nutrient absorption, or microbiota interactions. The gut is integral to human immunity and digestion, and any active molecules usually aid these processes. + +2. **Role in Pathways Specific to Gut**: Common pathways in the gut include inflammatory signaling (e.g., IL-6 signaling as seen in Crohn’s disease), gut-brain axis communications, and pathways regulating gastrointestinal homeostasis and motility. If 'Ractive{gut}' is involved in these or similar pathways, it could play a regulatory role in maintaining gut health. + +3. **Interactions with Other Molecules in the Gut**: In the gut, molecules often interact with cytokines, receptors, or microorganisms. For example, IL-6 interacts with its receptors to mediate immune responses. Similar interactions might apply to 'Ractive{gut}' if it pertains to immune regulation. + +4. **Importance of Gut Location**: The gut location is crucial for any biological molecule involved in digestive or immune processes, as the gut environment hosts a unique microbiota and a distinct immune milieu that influence overall health. + +Overall, without specific details in the context, these inferences are based on typical characteristics and functions of biological agents in gut physiology and pathology." +mw2b255f94_8018_4b99_bde8_918eeac45446,STAT3{gut},STAT3,gut,"The context provided does not include specific information about the biological function, pathway roles, or molecular interactions of the species named 'STAT3{gut}' in the gut specifically. However, based on general knowledge of STAT3 (Signal Transducer and Activator of Transcription 3) and its role in various tissues, here is a summary and inference about its function in the gut: + +1. **Biological Function in Gut**: + - STAT3 is a transcription factor that is activated through phosphorylation, typically by cytokine signaling (e.g., IL-6 signaling). In the context of the gut, STAT3 is likely involved in mediating inflammatory responses and maintaining mucosal integrity. Its activation can lead to the expression of various genes involved in inflammation and immune responses. + +2. **Role in Gut-Specific Pathways**: + - In the gut, STAT3 is primarily involved in pathways associated with inflammation and immune regulation. Particularly, it is activated by IL-6 through classical IL-6 receptor complex signaling or trans-signaling involving soluble IL-6 receptors (sIL-6Rα). This pathway is crucial in conditions like inflammatory bowel diseases (IBD), such as Crohn's disease, where elevated IL-6 levels and subsequent STAT3 activation have been implicated. + +3. **Interactions with Other Molecules in Gut**: + - STAT3 interacts with various cytokines and receptors. In the gut, it is activated by IL-6 binding to its receptor, which subsequently activates the Janus kinase (JAK) family, leading to STAT3 phosphorylation (pSTAT3). The activated STAT3 then dimerizes and translocates to the nucleus to initiate transcription of target genes. It may also interact with other molecules like SOCS (Suppressor of Cytokine Signaling), which act as negative regulators. + +4. **Importance of Gut Location**: + - The specific location of STAT3 in the gut is important due to the organ's role in nutrient absorption, barrier function, and as a critical site of immune interaction with the external environment. Aberrations in STAT3 signaling can lead to dysregulated immune responses and are associated with diseases like IBD, as indicated by increased STAT3 activation in colon biopsies of affected individuals. + +In summary, though the document does not provide direct insights into 'STAT3{gut}', the general knowledge about STAT3 suggests its significant role in regulating immune responses and maintaining intestinal health, especially under inflammatory conditions." +mw48867e93_f170_44e8_ac7a_185b23e1bf3b,pSTAT3{gut},pSTAT3,gut,"The provided context does not contain direct information about the biological species 'pSTAT3{gut}' in the gut compartment. However, based on general knowledge about the role of phosphorylated STAT3 (pSTAT3) in biological systems, particularly in the gastrointestinal (GI) tract, we can infer some functions and interactions. + +1. **Biological Function in the Gut:** + - pSTAT3 is a phosphorylated form of STAT3, which is a transcription factor activated through cytokine signaling pathways, primarily via the IL-6 receptor. In the gut, it is likely involved in regulating inflammation, aiding in the maintenance of the epithelial barrier, and potentially influencing cellular proliferation and differentiation. + +2. **Role in Pathways Specific to the Gut:** + - In the context of the gastrointestinal tract, pSTAT3 is often activated in response to cytokines such as IL-6. It plays a crucial role in mediating inflammatory responses. The document notes an increase in pSTAT3 in colon biopsies of patients with Crohn's Disease, indicating its involvement in the pathogenesis of inflammatory bowel diseases (IBD). + +3. **Interactions with Other Molecules in the Gut:** + - pSTAT3 is part of the signaling cascade that involves IL-6 and its soluble receptor sIL-6R. IL-6 binds to its receptors, leading to the activation of gp130, which subsequently activates JAK kinases and results in the phosphorylation of STAT3. The IL-6/sIL-6R complex can be inhibited by sgp130, limiting pSTAT3 activation. + +4. **Importance of the Gut Location:** + - The gut is a critical compartment for immune system interactions due to its role as a barrier and site for nutrient absorption. pSTAT3's role in the gut is pivotal for managing gut homeostasis and inflammatory responses, which are essential for maintaining a balanced immune response while preventing chronic inflammation and autoimmune reactions. + +Overall, while the document does not provide detailed specific insights into 'pSTAT3{gut}', the inference can be made based on the typical role of pSTAT3 in inflammation and immunity within the gastrointestinal context, especially concerning its involvement in inflammatory bowel diseases." +mw0083d743_836f_4238_a17f_4602193d5bc0,geneProduct{gut},geneProduct,gut,"Based on the context provided, there appears to be no specific mention of the species named 'geneProduct{gut}' within the gut compartment described by the ID mw0083d743_836f_4238_a17f_4602193d5bc0. Therefore, I will infer the possible biological significance of this entity based on general knowledge about gene products in the gut. + +### Inferred Information about 'geneProduct{gut}' in the Gut: + +1. **Biological Function in the Gut:** + - Gene products in the gut commonly include enzymes, structural proteins, and signaling molecules that facilitate digestion, maintain gut integrity, and manage immune responses. + - A gene product in the gut could potentially be involved in the breakdown of nutrients, absorption processes, or the formation of the gut barrier. + +2. **Role in Gut-Specific Pathways:** + - Gene products can be integral to pathways related to nutrient metabolism, such as carbohydrate and protein digestion. + - They may also participate in signaling pathways central to gut homeostasis and protection against pathogens, such as the NF-kB signaling pathway involved in inflammatory responses. + +3. **Interactions with Other Molecules in the Gut:** + - Interactions could include binding with receptors on gut epithelial cells, collaborating with microbiota to aid in digestion, or modulating immune cell activity within the gut mucosa. + - Inflammatory cytokines like IL-6 are mentioned in the context; thus, 'geneProduct{gut}' could interact with these or similar molecules influencing inflammatory or anti-inflammatory responses. + +4. **Importance of Gut Location:** + - The gut location is crucial as it provides a unique environment where complex processes like digestion and immune surveillance occur. + - Being in the gut allows for direct interaction with ingested substances and a close association with the gut microbiome, influencing both physiological and pathological states. + +Understanding these inferred roles can provide insights into the potential biological relevance of 'geneProduct{gut}' in maintaining gut health and function." +mwd31f52cc_04e7_40e0_885f_c7b2d9e62215,sR{gut},sR,gut,"The context provided does not contain specific information about a species named 'sR{gut}' directly in the gut compartment with ID 'mwd31f52cc_04e7_40e0_885f_c7b2d9e62215'. However, there are references to related molecules and processes involving the gut, specifically related to IL-6, sIL-6R, and other components involved in trans-signaling pathways. + +### Inferred Background: +1. **Biological Function in the Gut:** + - **IL-6 and IL-6 Receptors:** IL-6 is a cytokine involved in inflammatory response. In the gut, it can influence immune responses and gut barrier integrity. + - **sIL-6R (soluble IL-6 receptor):** This soluble form of the IL-6 receptor is involved in the IL-6 trans-signaling pathway, which can enhance IL-6 activity and influence gut inflammation and other responses. + +2. **Role in Pathways Specific to the Gut:** + - The mentioned components are part of a pathway that involves the IL-6 trans-signaling via sIL-6R and sgp130. This pathway can lead to the activation of STAT3, a transcription factor that influences gene expression in response to cytokine signaling. This pathway is significant in the gut as it can affect immune responses and inflammation levels. + +3. **Interactions with Other Molecules in the Gut:** + - IL-6 in the gut interacts with its receptors (both membrane-bound and soluble, like sIL-6R) and with sgp130, which can modulate the downstream effects of IL-6 signaling. This can lead to the activation of STAT3 and production of proteins like CRP (C-reactive protein) that act as markers of inflammation. + +4. **Importance of Gut Location for this Species:** + - The presence and function of IL-6, its receptors, and associated signaling molecules like pSTAT3 in the gut are crucial for regulating local immune responses and maintaining gut homeostasis. High local concentrations of these molecules in the gut are indicative of an active response to inflammation or infections. + +### General Inference: +Given that 'sR{gut}' is not specifically mentioned, it's possible it relates to soluble receptors or regulator proteins similar to sIL-6R, which, in a broad sense, play a role in modulating cytokine activity and influencing inflammatory responses in the gut. Such components are critical in maintaining gut tissue health and responding to pathological conditions by participating in signaling pathways that regulate immune cell activity and response to injury or infection." +mw2c9b0499_3325_4394_8af3_bbf653a944a0,IL6{gut},IL6,gut,"Based on the context provided, IL6{gut} likely refers to interleukin-6 (IL-6) within the gut compartment. Here is a summary of relevant background information about IL-6 in the gut: + +1. **Biological Function in the Gut**: + - IL-6 is a cytokine that plays a key role in the inflammatory response within the gut. It is particularly known for its involvement in inflammatory bowel diseases like Crohn's disease. + - In the gut, IL-6 contributes to enhanced T-cell survival and resistance to apoptosis (programmed cell death) in the lamina propria, which is a key area within the intestinal mucosa. + - IL-6 signaling is accompanied by elevated secretion of chemokines, which are signaling proteins that attract cells to sites of inflammation. + +2. **Role in Gut-Specific Pathways**: + - IL-6 signaling in the gut can occur through two pathways: the classical pathway via membrane-bound IL-6 receptor (IL-6Rα) and the trans-signaling pathway via soluble IL-6 receptor (sIL-6Rα). + - In both pathways, the IL-6/IL-6R complex can recruit the gp130 coreceptor, forming a receptor complex that triggers further intracellular signaling. + - The activation of this signaling cascade leads to the phosphorylation of Janus kinase (Jak) family proteins and the STAT3 protein, which are crucial for propagating inflammatory signals. + +3. **Interactions with Other Molecules in the Gut**: + - IL-6 interacts with both its membrane-bound and soluble receptors, orchestrating a complex signaling mechanism crucial for mediating inflammatory responses. + - The presence of soluble forms of the gp130 receptor in humans can inhibit signals through membrane-anchored gp130, impacting the extent and nature of IL-6 signaling. + +4. **Importance of Gut Location**: + - In the context of gut inflammation and diseases like Crohn's disease, the local production and activity of IL-6 are critical. The gut represents a unique microenvironment where immune responses can have significant impacts on health and disease. + - Elevated IL-6 levels in the gut are associated with increased disease activity in conditions like Crohn's disease, highlighting its importance in local tissue-specific signaling and responses. + +These insights emphasize IL-6's significant role in the gut's immune and inflammatory environments, particularly in the context of inflammatory diseases." +mwd65b5b39_dc1b_4e77_a999_67277a880e5e,sgp130{gut},sgp130,gut,"The species 'sgp130{gut}', likely derived from the soluble form of the cell surface receptor gp130, is involved primarily in inhibiting IL-6 trans-signaling. This biological function is significant because IL-6 is a cytokine involved in inflammatory processes, and its overactivity is implicated in several diseases, including those affecting the gut, such as Crohn's disease. + +### Biological Function in Gut +- **Inhibition of IL-6 Trans-signaling:** sgp130 functions by binding the IL-6/sIL-6Rα complex, thereby preventing IL-6 from interacting with membrane-bound gp130, which would otherwise result in pro-inflammatory signaling. + +### Role in Pathways Specific to Gut +- **IL-6 Pathway Modulation:** In the gut, by inhibiting IL-6 trans-signaling, sgp130 can potentially modulate inflammatory responses, which are crucial in maintaining gut homeostasis and protecting against inflammatory diseases such as Crohn's disease. + +### Interactions with Other Molecules +- **Binding to IL-6/sIL-6Rα Complex:** sgp130 specifically interacts with the IL-6/sIL-6Rα complex to inhibit its activity. This suggests a critical role in regulating cytokine-driven signaling pathways which can lead to inflammation if unchecked. + +### Importance of Gut Location +- **Local Inflammatory Regulation:** The presence of sgp130 in the gut is particularly important for local regulation of inflammation. Given the gut's exposure to a myriad of antigens and its role in immune responses, effective modulation of signaling pathways like those of IL-6 is crucial. + +### General Knowledge Inference +While the document does not provide specific details on 'sgp130{gut}' within this compartment, based on the general role of sgp130 in modulating IL-6 pathways, it can be inferred that its presence in the gut is vital for managing localized inflammatory responses. The context suggests its potential therapeutic use in conditions like Crohn's disease, where inflammation is a key concern. + +### Limitations and Effectiveness +- **Baseline Levels:** The high baseline levels of sgp130, as indicated, suggest its effects might not be substantial unless administered in large amounts. +- **Therapeutic Potential:** Current therapeutic strategies involving sgp130, such as sgp130Fc, need high and frequent dosing to be effective, possibly due to the large excess of sgp130 over IL-6, underscoring the need for alternative or complementary approaches. + +Overall, sgp130 in the gut likely plays a crucial but contextually limited role in controlling inflammation via IL-6 trans-signaling inhibition." +mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3,sR_IL6_sgp130{gut},sR_IL6_sgp130,gut,"Based on the provided context and general knowledge, the species 'sR_IL6_sgp130{gut}' in the gut compartment appears to be related to a soluble form of gp130, which serves as a natural inhibitor of interleukin-6 (IL-6) trans-signaling. Here is a summary of relevant information: + +1. **Biological Function in Gut**: + - The 'sR_IL6_sgp130' is associated with inhibiting IL-6 trans-signaling. IL-6 is a cytokine involved in inflammation and immune response regulation. + - In the gut, particularly in conditions like Crohn’s disease, the modulation of IL-6 signaling is crucial due to its role in inflammatory processes. + +2. **Role in Pathways Specific to Gut**: + - The IL-6 pathway is significant in the gastrointestinal tract for its involvement in immune system signaling and inflammatory responses. + - The soluble gp130 (sgp130) acts by binding to the IL-6/sIL-6Rα complex, thereby preventing it from interacting with membrane-bound gp130, which is necessary for downstream signaling events that lead to inflammation. + +3. **Interactions with Other Molecules in Gut**: + - 'sR_IL6_sgp130' interacts with IL-6 and the soluble IL-6 receptor (sIL-6R). This interaction prevents further binding and signaling through membrane-bound gp130. + - The context suggests that sgp130Fc, a fusion protein incorporating sgp130, could potentially interfere with this signaling pathway, thus offering a therapeutic option for inflammatory conditions like Crohn’s disease in the gut. + +4. **Importance of Gut Location for this Species**: + - The gut is a critical location due to its role in immune response and inflammation, which are central in conditions such as inflammatory bowel diseases. + - The presence of sR_IL6_sgp130 in the gut highlights the region-specific regulation of inflammation through cytokine signaling pathways. + +In summary, 'sR_IL6_sgp130{gut}' serves as a modulator of IL-6 mediated signaling, particularly in inflammatory contexts such as those encountered in the gut. Its role as an inhibitory agent is crucial for managing inflammatory diseases like Crohn’s disease and underscores the importance of targeted therapies in such conditions." +mwf7796221_1fea_4274_a93e_c00adbf5778c,Ab{gut},Ab,gut,"Based on the context provided and general knowledge, the specific species ""Ab{gut}"" in the gut compartment (ID: mwf7796221_1fea_4274_a93e_c00adbf5778c) is not explicitly detailed in the content supplied. Therefore, let's infer potential roles and functions based on knowledge of antibodies (Ab) and gut biology: + +1. **Biological Function in the Gut:** + - Antibodies in the gut, often referred to as immunoglobulins, play a critical role in the immune defense by identifying and neutralizing pathogens, such as bacteria and viruses. In the gut, immunoglobulin A (IgA) is predominant, contributing to mucosal immunity and maintaining gut homeostasis. + +2. **Role in Pathways Specific to the Gut:** + - In the gastrointestinal tract, antibodies are involved in immune surveillance and the maintenance of the mucosal barrier. They participate in pathways that manage the balance between immune response and tolerance, preventing overreaction to commensal microbes while responding to pathogens. + +3. **Interactions with Other Molecules in the Gut:** + - Antibodies interact with antigens presented by invading pathogens or commensal bacteria in the gut lumen. This interaction helps to prevent pathogen adhesion and facilitates their removal by agglutination or neutralization. They also work in tandem with other gut immune cells, like macrophages and dendritic cells, to orchestrate a coordinated immune response. + +4. **Importance of Gut Location for This Species:** + - The localization of antibodies in the gut is crucial because the gut acts as a major entry point for pathogens. Maintaining a robust immune barrier is essential for preventing infections. The gut-associated lymphoid tissue (GALT) serves as an immune surveillance site, where antibodies are instrumental in detecting and responding to threats. + +In summary, if ""Ab{gut}"" refers to an antibody species within the gut, it likely plays a key role in maintaining immune homeostasis, interacting with pathogen-associated molecules, and integrating into gut-specific immune pathways to ensure the proper functioning of the gastrointestinal immune system." +mw5d764bb8_5693_4ac8_9557_f65992cc5eb0,Ab_sR{gut},Ab_sR,gut,"The context provided does not contain specific information about a species explicitly named 'Ab_sR{gut}' in the gut compartment. However, based on the typical nomenclature and the content from the document, here's what can be inferred: + +1. **Biological Function in Gut:** + - The IL-6 signaling pathway is highly posited in the excerpts, where IL-6 complexes with its soluble receptor (sIL-6R) to engage in signaling mechanisms. This might suggest that 'Ab_sR{gut}' could be related to similar cytokine activity and modulation within the gut. + +2. **Role in Gut-Specific Pathways:** + - Cytokines like IL-6 are integral to immune responses and inflammation in the gastrointestinal tract. They can induce the activation of STAT3, a transcription factor known to play a role in the inflammatory responses as noted in cases such as inflammatory bowel disease (IBD). Therefore, it is plausible that 'Ab_sR{gut}' could be involved in pathways related to local immune responses in the gut. + +3. **Interactions with Other Molecules:** + - If 'Ab_sR{gut}' functions similarly to known soluble receptors in gut environments, it may interact with other cytokines, their receptors, or signaling molecules like STAT3. These interactions are crucial for transmitting signals that regulate cellular responses within the gut microenvironment. + +4. **Importance of Gut Location:** + - The localization within the gut is essential for immune surveillance and response to pathogens or dietary antigens. Molecules like IL-6 and their soluble receptors need to be active and regulated in such compartments to manage local inflammatory responses efficiently. Therefore, the gut location could be significant for 'Ab_sR{gut}' in contributing to or modulating local immune processes. + +In summary, while direct information about 'Ab_sR{gut}' is not available, by inference from similar gut proteins, it likely plays a role in immune modulation and inflammatory signaling within the gut, interacting with cytokines and other signaling molecules to maintain gut homeostasis and respond to inflammatory challenges." +mwedc1bc00_adf7_4144_a1c2_7dc1a9565dc2,Ab_sR_IL6{gut},Ab_sR_IL6,gut,"The context does not provide explicit information on a species named 'Ab_sR_IL6{gut}'. However, based on the provided documents related to IL-6 and its receptor interactions in the gut, we can offer some insights based on general knowledge about similar biological components such as IL-6, sIL-6R (soluble IL-6 receptor), and their interactions. + +### Biological Function in the Gut + +IL-6 is a cytokine involved in various biological processes, including inflammation and immune responses. In the gut, IL-6 plays a key role in modulating immune responses and maintaining mucosal homeostasis. It is involved in the inflammatory processes often associated with gastrointestinal diseases like Crohn’s disease. + +### Role in Gut-Specific Pathways + +The document references the IL-6/sIL-6Rα complex and its role in Crohn’s disease, suggesting that this pathway is significant in gut immune regulation. The binding of IL-6 to its soluble receptor, sIL-6R, enables the formation of a complex that can engage gp130, initiating downstream signaling pathways. This leads to the activation of STAT3, a transcription factor, which induces the expression of various genes involved in the inflammatory response. + +### Interactions with Other Molecules in the Gut + +The IL-6/sIL-6R complex's primary interaction in the gut involves gp130, which is a signal transducer for various cytokine receptors. The subsequent activation of STAT3 is critical for mediating gene expression changes that result in inflammatory and immune responses. Moreover, CRP (C-reactive protein) is mentioned as part of the systemic response to IL-6, which might have implications for inflammation at the gut level. + +### Importance of Gut Location + +The gut is an essential component of the immune system, housing a significant portion of the body's immune cells. The specific presence and activity of IL-6 and its soluble receptor in the gut point to a specialized role in maintaining gut homeostasis and responding to pathogenic threats. The location in the gut is crucial for directly influencing local immune responses and potentially systemic inflammation through the production of inflammatory mediators like CRP. + +In summary, while 'Ab_sR_IL6{gut}' is not specifically described in the context, by analogy to sIL-6R and IL-6 pathways in the gut, one could infer that it likely plays a significant role in local immune regulation and inflammation through interaction with other molecules like gp130 and contributing to conditions such as Crohn’s disease." +mwbc2f5464_81e5_43fd_8b39_f5a2756af72f,Ab{peripheral},Ab,peripheral,"The context provided does not explicitly mention the species 'Ab{peripheral}' or provide specific details about its function, role in pathways, interactions, or the importance of its peripheral location. However, based on general knowledge about antibodies (often abbreviated as Ab), particularly in peripheral compartments such as the blood and tissues, I can infer some possibilities. + +1. **Biological Function in Peripheral:** + - Antibodies in peripheral tissues typically function as part of the immune response. They identify and neutralize foreign objects like bacteria and viruses. + +2. **Role in Pathways Specific to Peripheral:** + - In peripheral compartments, antibodies can participate in immune signaling pathways. They may interact with components of the complement system, enhance phagocytosis by binding to Fc receptors on immune cells, and neutralize toxins or pathogens. + +3. **Interactions with Other Molecules in Peripheral:** + - Antibodies frequently interact with antigens, which could be proteins or polysaccharides on the surfaces of pathogens or transformed cells. + - They can form immune complexes with soluble antigens, which may then be cleared by macrophages in the peripheral blood. + - Antibodies can also recruit other immune cells to an infection site through Fc receptor binding. + +4. **Importance of Peripheral Location for This Species:** + - The peripheral location is critical for antibodies as it enables them to circulate throughout the body and provide a rapid response to systemic infections. + - Peripheral distribution allows antibodies to access various tissues and compartments, crucial for a comprehensive immune defense. + +Without specific information about 'Ab{peripheral}' from the context, these inferences are based on the typical roles and functions of antibodies in peripheral systems such as the circulatory or lymphatic systems. Further details would require more specific data or references from the document." From ea786edd887cd7fbe98b3b2b6f2baa89e736b889 Mon Sep 17 00:00:00 2001 From: Inigo Date: Fri, 7 Mar 2025 16:23:32 +0000 Subject: [PATCH 14/14] Clean up --- notebook/embeddings_and_evaluation.ipynb | 30 +- notebook/subgraph_generation.ipynb | 3769 ---------------------- 2 files changed, 23 insertions(+), 3776 deletions(-) delete mode 100644 notebook/subgraph_generation.ipynb diff --git a/notebook/embeddings_and_evaluation.ipynb b/notebook/embeddings_and_evaluation.ipynb index 2b3926cd..5211fd3e 100644 --- a/notebook/embeddings_and_evaluation.ipynb +++ b/notebook/embeddings_and_evaluation.ipynb @@ -197,7 +197,7 @@ }, { "cell_type": "code", - "execution_count": 8, + "execution_count": 23, "id": "d9c7affa-2558-433d-a3b1-b5dcf31b7ccd", "metadata": {}, "outputs": [], @@ -209,12 +209,28 @@ " inputs = tokenizer(text, return_tensors='pt', truncation=True, padding=True, max_length=512)\n", " outputs = model(**inputs)\n", " \n", - " return outputs.last_hidden_state.mean(dim=1).detach().numpy() # Shape: (1, hidden_size)\n", - "\n", - "# Example: Get embedding for a species description\n", - "text_description = \"\"\"\n", - " IL1B belongs to gene/protein category. The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. Similarly, IL-1B has been implicated in human osteoarthritis pathogenesis. Patients with severe Coronavirus Disease 2019 (COVID-19) present elevated levels of pro-inflammatory cytokines such as IL-1B in bronchial alveolar lavage fluid samples. The lung damage induced by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to a large extent, a result of the inflammatory response promoted by cytokines such as IL-1B. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2\"\"\"\n", - "text_embedding = get_text_embedding(text_description)\n" + " return outputs.last_hidden_state.mean(dim=1).detach().numpy() # Shape: (1, hidden_size)" + ] + }, + { + "cell_type": "code", + "execution_count": 24, + "id": "110c035e-8293-4383-8f37-4b820dc23b92", + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "\"SMAD3 belongs to gene/protein category. The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022].\"" + ] + }, + "execution_count": 24, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "G.nodes[nodes_list[0]]['enriched_node']" ] }, { diff --git a/notebook/subgraph_generation.ipynb b/notebook/subgraph_generation.ipynb deleted file mode 100644 index f2763936..00000000 --- a/notebook/subgraph_generation.ipynb +++ /dev/null @@ -1,3769 +0,0 @@ -{ - "cells": [ - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "# PrimeKG Subgraph Construction" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "In this tutorial, we will showcase how to construct a subraph from PrimeKG and prepare necessary graph formats for further analysis.\n", - "\n", - "In particular, we will slice a subgraph from PrimeKG related to inflammatory bowel disease (IBD).\n", - "\n", - "The subgraph will contain all nodes and edges that are connected to IBD-related disease nodes, including the following relationships:\n", - "- Disease-Protein Relationship\n", - "- Disease-Disease Relationship (skipped as of now)\n", - "- Protein-Protein Relationship (skipped as of now)\n", - "- Drug-Protein Relationship\n", - "- Pathway-Protein Relationship\n", - "- Pathway-Pathway Relationship (skipped as of now)\n", - "- Bioprocess-Protein Relationship\n", - "- Molecular Function-Protein Relationship\n", - "- Cellular Component-Protein Relationship" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "In addition, to enrich the nodes and edges, we will perform the following tasks:\n", - "- Textual enrichment (only this task is implemented as of now) \n", - "- Multi-modal enrichment (to be added)" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "\n", - "First of all, we need to import necessary libraries as follows:" - ] - }, - { - "cell_type": "code", - "execution_count": 3, - "metadata": {}, - "outputs": [], - "source": [ - "# Import necessary libraries\n", - "import os\n", - "import numpy as np\n", - "import pandas as pd\n", - "import networkx as nx\n", - "import pickle\n", - "from tqdm import tqdm\n", - "from torch_geometric.utils import from_networkx\n", - "import sys\n", - "sys.path.append('../')\n", - "from aiagents4pharma.talk2knowledgegraphs.datasets.primekg import PrimeKG\n", - "from aiagents4pharma.talk2knowledgegraphs.datasets.starkqa_primekg import StarkQAPrimeKG\n", - "from aiagents4pharma.talk2knowledgegraphs.utils.embeddings.ollama import EmbeddingWithOllama\n", - "from aiagents4pharma.talk2knowledgegraphs.utils import kg_utils\n", - "\n", - "# # Set the logging level for httpx to WARNING to suppress INFO messages\n", - "import logging\n", - "logging.getLogger(\"httpx\").setLevel(logging.WARNING)" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "### PrimeKG" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "We utilize the `PrimeKG` class from the aiagents4pharma/talk2knowledgegraphs library.\n", - "\n", - "The `PrimeKG` needs to be initialized with the path to the PrimeKG dataset to be stored/loaded from the local directory." - ] - }, - { - "cell_type": "code", - "execution_count": 4, - "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "Loading nodes of PrimeKG dataset ...\n", - "../../data/primekg/primekg_nodes.tsv.gz already exists. Loading the data from the local directory.\n", - "Loading edges of PrimeKG dataset ...\n", - "../../data/primekg/primekg_edges.tsv.gz already exists. Loading the data from the local directory.\n" - ] - } - ], - "source": [ - "# Define primekg data by providing a local directory where the data is stored\n", - "primekg_data = PrimeKG(local_dir=\"../../data/primekg/\")\n", - "\n", - "# Invoke a method to load the data\n", - "primekg_data.load_data()\n", - "\n", - "# Get primekg_nodes and primekg_edges\n", - "primekg_nodes = primekg_data.get_nodes()\n", - "primekg_edges = primekg_data.get_edges()" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "### IBD-related Data Filtering" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### IBD-related Disease Nodes" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "As a first step, we will perform data filtering over the primekg_nodes by querying the nodes that contains the following terms:\n", - "- inflammatory bowel disease\n", - "- crohn\n", - "- ulcerative colitis\n", - "\n", - "As of now, this basic query is used to filter the data. However, this can be replaced with a more complex query that can capture more nodes related to IBD." - ] - }, - { - "cell_type": "code", - "execution_count": 31, - "metadata": {}, - "outputs": [ - { - "name": "stderr", - "output_type": "stream", - "text": [ - "/tmp/ipykernel_1377/1976418716.py:14: UserWarning: This pattern is interpreted as a regular expression, and has match groups. To actually get the groups, use str.extract.\n", - " ibd_nodes_df = ibd_nodes_df[ibd_nodes_df.node_type == \"disease\"].query(query_str, engine='python')\n" - ] - }, - { - "data": { - "text/html": [ - "
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node_indexnode_namenode_sourcenode_idnode_type
3564935649neoplasm of mature T-cells or NK-cellsMONDO5169disease
3581435814Crohn ileitis and jejunitisMONDO_grouped709_21207disease
3581535815small bowel Crohn diseaseMONDO5539disease
3778437784Crohn diseaseMONDO_grouped5011_5535disease
8377083770Crohn's colitisMONDO5532disease
9527995279Crohn jejunoileitisMONDO708disease
9528095280gastroduodenal Crohn diseaseMONDO710disease
9708897088perianal Crohn diseaseMONDO5537disease
9932599325Crohn disease of the esophagusMONDO22901disease
\n", - "
" - ], - "text/plain": [ - " node_index node_name node_source \\\n", - "35649 35649 neoplasm of mature T-cells or NK-cells MONDO \n", - "35814 35814 Crohn ileitis and jejunitis MONDO_grouped \n", - "35815 35815 small bowel Crohn disease MONDO \n", - "37784 37784 Crohn disease MONDO_grouped \n", - "83770 83770 Crohn's colitis MONDO \n", - "95279 95279 Crohn jejunoileitis MONDO \n", - "95280 95280 gastroduodenal Crohn disease MONDO \n", - "97088 97088 perianal Crohn disease MONDO \n", - "99325 99325 Crohn disease of the esophagus MONDO \n", - "\n", - " node_id node_type \n", - "35649 5169 disease \n", - "35814 709_21207 disease \n", - "35815 5539 disease \n", - "37784 5011_5535 disease \n", - "83770 5532 disease \n", - "95279 708 disease \n", - "95280 710 disease \n", - "97088 5537 disease \n", - "99325 22901 disease " - ] - }, - "execution_count": 31, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Query for nodes related to IBD\n", - "\n", - "relevant_terms = [\"Crohn\", \"Interleukin-6\", \"T-cells\", \"(IL-6)\"]\n", - "query_str = \"\"\n", - "for idx in range(len(relevant_terms)): # Assuming relevant_terms is a list\n", - " if idx == 0:\n", - " query_str += f'node_name_lower.str.contains(\"{relevant_terms[idx].lower()}\")'\n", - " else:\n", - " query_str += f'or node_name_lower.str.contains(\"{relevant_terms[idx].lower()}\")'\n", - "\n", - "# Get the nodes related to IBD\n", - "ibd_nodes_df = primekg_nodes.copy()\n", - "ibd_nodes_df[\"node_name_lower\"] = primekg_nodes.node_name.apply(lambda x: x.lower())\n", - "ibd_nodes_df = ibd_nodes_df[ibd_nodes_df.node_type == \"disease\"].query(query_str, engine='python')\n", - "ibd_nodes_df.drop(columns=[\"node_name_lower\"], inplace=True)\n", - "ibd_nodes_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Disease-Protein Relationship\n" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Based on the nodes related to IBD, we can further capture the records containing the relationships of disease-gene/protein nodes." - ] - }, - { - "cell_type": "code", - "execution_count": 6, - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
601839537784Crohn diseaseMONDO_grouped5011_5535disease2384CRPNCBI1401gene/proteinassociated withdisease_protein
601839783770Crohn's colitisMONDO5532disease2384CRPNCBI1401gene/proteinassociated withdisease_protein
601839837784Crohn diseaseMONDO_grouped5011_5535disease3088DNMT3ANCBI1788gene/proteinassociated withdisease_protein
601840083770Crohn's colitisMONDO5532disease3088DNMT3ANCBI1788gene/proteinassociated withdisease_protein
601840137784Crohn diseaseMONDO_grouped5011_5535disease2057FN1NCBI2335gene/proteinassociated withdisease_protein
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330446834887DENND1BNCBI163486gene/protein35814Crohn ileitis and jejunitisMONDO_grouped709_21207diseaseassociated withdisease_protein
330446913365CCNYNCBI219771gene/protein35814Crohn ileitis and jejunitisMONDO_grouped709_21207diseaseassociated withdisease_protein
330447035156FAM92BNCBI339145gene/protein35814Crohn ileitis and jejunitisMONDO_grouped709_21207diseaseassociated withdisease_protein
330447134780IRGMNCBI345611gene/protein35814Crohn ileitis and jejunitisMONDO_grouped709_21207diseaseassociated withdisease_protein
33102775022ITGAMNCBI3684gene/protein35814Crohn ileitis and jejunitisMONDO_grouped709_21207diseaseassociated withdisease_protein
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290 rows × 12 columns

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" - ], - "text/plain": [ - " head_index head_name head_source head_id head_type \\\n", - "6018395 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", - "6018397 83770 Crohn's colitis MONDO 5532 disease \n", - "6018398 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", - "6018400 83770 Crohn's colitis MONDO 5532 disease \n", - "6018401 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", - "... ... ... ... ... ... \n", - "3304468 34887 DENND1B NCBI 163486 gene/protein \n", - "3304469 13365 CCNY NCBI 219771 gene/protein \n", - "3304470 35156 FAM92B NCBI 339145 gene/protein \n", - "3304471 34780 IRGM NCBI 345611 gene/protein \n", - "3310277 5022 ITGAM NCBI 3684 gene/protein \n", - "\n", - " tail_index tail_name tail_source tail_id \\\n", - "6018395 2384 CRP NCBI 1401 \n", - "6018397 2384 CRP NCBI 1401 \n", - "6018398 3088 DNMT3A NCBI 1788 \n", - "6018400 3088 DNMT3A NCBI 1788 \n", - "6018401 2057 FN1 NCBI 2335 \n", - "... ... ... ... ... \n", - "3304468 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", - "3304469 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", - "3304470 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", - "3304471 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", - "3310277 35814 Crohn ileitis and jejunitis MONDO_grouped 709_21207 \n", - "\n", - " tail_type display_relation relation \n", - "6018395 gene/protein associated with disease_protein \n", - "6018397 gene/protein associated with disease_protein \n", - "6018398 gene/protein associated with disease_protein \n", - "6018400 gene/protein associated with disease_protein \n", - "6018401 gene/protein associated with disease_protein \n", - "... ... ... ... \n", - "3304468 disease associated with disease_protein \n", - "3304469 disease associated with disease_protein \n", - "3304470 disease associated with disease_protein \n", - "3304471 disease associated with disease_protein \n", - "3310277 disease associated with disease_protein \n", - "\n", - "[290 rows x 12 columns]" - ] - }, - "execution_count": 6, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# IBD disease_protein edges\n", - "ibd_disease_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_index.isin(ibd_nodes_df.index.values)) & \n", - " (primekg_edges.tail_type == 'gene/protein')],\n", - " primekg_edges[(primekg_edges.tail_index.isin(ibd_nodes_df.index.values)) & \n", - " (primekg_edges.head_type == 'gene/protein')]])\n", - "\n", - "# Check dataframe\n", - "ibd_disease_protein_edges_df" - ] - }, - { - "cell_type": "code", - "execution_count": 7, - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "array([ 144, 729, 989, 1122, 1480, 1567, 1618, 2057, 2111,\n", - " 2329, 2384, 2983, 3088, 3259, 3333, 3469, 3484, 3495,\n", - " 4162, 4997, 5022, 5195, 5385, 5720, 5915, 6168, 6175,\n", - " 6229, 6428, 6661, 7059, 7083, 7899, 7958, 10113, 10191,\n", - " 11134, 11523, 12305, 12663, 12763, 12816, 13014, 13365, 22105,\n", - " 34778, 34779, 34780, 34814, 34887, 35156])" - ] - }, - "execution_count": 7, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Get unique protein index\n", - "ibd_protein_index = np.unique(np.concatenate([ibd_disease_protein_edges_df[ibd_disease_protein_edges_df.head_type == 'gene/protein'].head_index.unique(),\n", - " ibd_disease_protein_edges_df[ibd_disease_protein_edges_df.tail_type == 'gene/protein'].tail_index.unique()]))\n", - "ibd_protein_index" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Disease-Disease Relationship" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Here, we can get the records containing the relationships of disease-disease nodes." - ] - }, - { - "cell_type": "code", - "execution_count": 8, - "metadata": {}, - "outputs": [], - "source": [ - "# # IBD disease_disease edges \n", - "# ibd_disease_disease_edges_df = pd.concat([primekg_edges[(primekg_edges.head_index.isin(ibd_nodes_df.index.values)) & \n", - "# (primekg_edges.tail_type == 'disease')],\n", - "# primekg_edges[(primekg_edges.tail_index.isin(ibd_nodes_df.index.values)) & \n", - "# (primekg_edges.head_type == 'disease')]])\n", - "\n", - "# # Check dataframe\n", - "# ibd_disease_disease_edges_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Protein-Protein Relationship" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "We also can get the records containing the relationships of gene/protein-gene/protein nodes." - ] - }, - { - "cell_type": "code", - "execution_count": 9, - "metadata": {}, - "outputs": [], - "source": [ - "# # IBD protein_protein edges \n", - "# ibd_protein_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_index.isin(ibd_protein_index)) & \n", - "# (primekg_edges.tail_type == 'gene/protein')],\n", - "# primekg_edges[(primekg_edges.tail_index.isin(ibd_protein_index)) & \n", - "# (primekg_edges.head_type == 'gene/protein')]])\n", - "\n", - "# # Check dataframe\n", - "# ibd_protein_protein_edges_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Drug-Protein Relationship" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Next, we will get the records containing the relationships of drug-gene/protein nodes." - ] - }, - { - "cell_type": "code", - "execution_count": 10, - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
32255914645MethionineDrugBankDB00134drug6175MTHFRNCBI4524gene/proteinenzymedrug_protein
32256014833RiboflavinDrugBankDB00140drug6175MTHFRNCBI4524gene/proteinenzymedrug_protein
32256114678Folic acidDrugBankDB00158drug6175MTHFRNCBI4524gene/proteinenzymedrug_protein
32256214834MenadioneDrugBankDB00170drug6175MTHFRNCBI4524gene/proteinenzymedrug_protein
32256314835BenazeprilDrugBankDB00542drug6175MTHFRNCBI4524gene/proteinenzymedrug_protein
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57307965385SLC22A4NCBI6583gene/protein14476Testosterone cypionateDrugBankDB13943drugtransporterdrug_protein
57307975385SLC22A4NCBI6583gene/protein14477Testosterone enanthateDrugBankDB13944drugtransporterdrug_protein
57307985385SLC22A4NCBI6583gene/protein14478Testosterone undecanoateDrugBankDB13946drugtransporterdrug_protein
57307995385SLC22A4NCBI6583gene/protein14654Choline salicylateDrugBankDB14006drugtransporterdrug_protein
57308005385SLC22A4NCBI6583gene/protein17318SolriamfetolDrugBankDB14754drugtransporterdrug_protein
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734 rows × 12 columns

\n", - "
" - ], - "text/plain": [ - " head_index head_name head_source head_id head_type \\\n", - "322559 14645 Methionine DrugBank DB00134 drug \n", - "322560 14833 Riboflavin DrugBank DB00140 drug \n", - "322561 14678 Folic acid DrugBank DB00158 drug \n", - "322562 14834 Menadione DrugBank DB00170 drug \n", - "322563 14835 Benazepril DrugBank DB00542 drug \n", - "... ... ... ... ... ... \n", - "5730796 5385 SLC22A4 NCBI 6583 gene/protein \n", - "5730797 5385 SLC22A4 NCBI 6583 gene/protein \n", - "5730798 5385 SLC22A4 NCBI 6583 gene/protein \n", - "5730799 5385 SLC22A4 NCBI 6583 gene/protein \n", - "5730800 5385 SLC22A4 NCBI 6583 gene/protein \n", - "\n", - " tail_index tail_name tail_source tail_id \\\n", - "322559 6175 MTHFR NCBI 4524 \n", - "322560 6175 MTHFR NCBI 4524 \n", - "322561 6175 MTHFR NCBI 4524 \n", - "322562 6175 MTHFR NCBI 4524 \n", - "322563 6175 MTHFR NCBI 4524 \n", - "... ... ... ... ... \n", - "5730796 14476 Testosterone cypionate DrugBank DB13943 \n", - "5730797 14477 Testosterone enanthate DrugBank DB13944 \n", - "5730798 14478 Testosterone undecanoate DrugBank DB13946 \n", - "5730799 14654 Choline salicylate DrugBank DB14006 \n", - "5730800 17318 Solriamfetol DrugBank DB14754 \n", - "\n", - " tail_type display_relation relation \n", - "322559 gene/protein enzyme drug_protein \n", - "322560 gene/protein enzyme drug_protein \n", - "322561 gene/protein enzyme drug_protein \n", - "322562 gene/protein enzyme drug_protein \n", - "322563 gene/protein enzyme drug_protein \n", - "... ... ... ... \n", - "5730796 drug transporter drug_protein \n", - "5730797 drug transporter drug_protein \n", - "5730798 drug transporter drug_protein \n", - "5730799 drug transporter drug_protein \n", - "5730800 drug transporter drug_protein \n", - "\n", - "[734 rows x 12 columns]" - ] - }, - "execution_count": 10, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# IBD drug_protein edges\n", - "ibd_drug_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'drug') & \n", - " (primekg_edges.tail_type == 'gene/protein') & \n", - " (primekg_edges.tail_index.isin(ibd_protein_index))], \n", - " primekg_edges[(primekg_edges.tail_type == 'drug') & \n", - " (primekg_edges.head_type == 'gene/protein') & \n", - " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", - "\n", - "# Check dataframe\n", - "ibd_drug_protein_edges_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Pathway-Protein Relationship" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "For this case, we will get the records containing the relationships of pathway-protein nodes." - ] - }, - { - "cell_type": "code", - "execution_count": 11, - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
6508862128783Metalloprotease DUBsREACTOMER-HSA-5689901pathway12305NLRP3NCBI114548gene/proteininteracts withpathway_protein
6508863128804The NLRP3 inflammasomeREACTOMER-HSA-844456pathway12305NLRP3NCBI114548gene/proteininteracts withpathway_protein
6508864129266Purinergic signaling in leishmaniasis infectionREACTOMER-HSA-9660826pathway12305NLRP3NCBI114548gene/proteininteracts withpathway_protein
650886563064Cytoprotection by HMOX1REACTOMER-HSA-9707564pathway12305NLRP3NCBI114548gene/proteininteracts withpathway_protein
6509093129136RHOA GTPase cycleREACTOMER-HSA-8980692pathway34814TAGAPNCBI117289gene/proteininteracts withpathway_protein
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383456011134NR1H4NCBI9971gene/protein128001Synthesis of bile acids and bile salts via 27-...REACTOMER-HSA-193807pathwayinteracts withpathway_protein
383456111134NR1H4NCBI9971gene/protein128393PPARA activates gene expressionREACTOMER-HSA-1989781pathwayinteracts withpathway_protein
383456211134NR1H4NCBI9971gene/protein62588Endogenous sterolsREACTOMER-HSA-211976pathwayinteracts withpathway_protein
383456311134NR1H4NCBI9971gene/protein128116Nuclear Receptor transcription pathwayREACTOMER-HSA-383280pathwayinteracts withpathway_protein
383456411134NR1H4NCBI9971gene/protein128204SUMOylation of intracellular receptorsREACTOMER-HSA-4090294pathwayinteracts withpathway_protein
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610 rows × 12 columns

\n", - "
" - ], - "text/plain": [ - " head_index head_name \\\n", - "6508862 128783 Metalloprotease DUBs \n", - "6508863 128804 The NLRP3 inflammasome \n", - "6508864 129266 Purinergic signaling in leishmaniasis infection \n", - "6508865 63064 Cytoprotection by HMOX1 \n", - "6509093 129136 RHOA GTPase cycle \n", - "... ... ... \n", - "3834560 11134 NR1H4 \n", - "3834561 11134 NR1H4 \n", - "3834562 11134 NR1H4 \n", - "3834563 11134 NR1H4 \n", - "3834564 11134 NR1H4 \n", - "\n", - " head_source head_id head_type tail_index \\\n", - "6508862 REACTOME R-HSA-5689901 pathway 12305 \n", - "6508863 REACTOME R-HSA-844456 pathway 12305 \n", - "6508864 REACTOME R-HSA-9660826 pathway 12305 \n", - "6508865 REACTOME R-HSA-9707564 pathway 12305 \n", - "6509093 REACTOME R-HSA-8980692 pathway 34814 \n", - "... ... ... ... ... \n", - "3834560 NCBI 9971 gene/protein 128001 \n", - "3834561 NCBI 9971 gene/protein 128393 \n", - "3834562 NCBI 9971 gene/protein 62588 \n", - "3834563 NCBI 9971 gene/protein 128116 \n", - "3834564 NCBI 9971 gene/protein 128204 \n", - "\n", - " tail_name tail_source \\\n", - "6508862 NLRP3 NCBI \n", - "6508863 NLRP3 NCBI \n", - "6508864 NLRP3 NCBI \n", - "6508865 NLRP3 NCBI \n", - "6509093 TAGAP NCBI \n", - "... ... ... \n", - "3834560 Synthesis of bile acids and bile salts via 27-... REACTOME \n", - "3834561 PPARA activates gene expression REACTOME \n", - "3834562 Endogenous sterols REACTOME \n", - "3834563 Nuclear Receptor transcription pathway REACTOME \n", - "3834564 SUMOylation of intracellular receptors REACTOME \n", - "\n", - " tail_id tail_type display_relation relation \n", - "6508862 114548 gene/protein interacts with pathway_protein \n", - "6508863 114548 gene/protein interacts with pathway_protein \n", - "6508864 114548 gene/protein interacts with pathway_protein \n", - "6508865 114548 gene/protein interacts with pathway_protein \n", - "6509093 117289 gene/protein interacts with pathway_protein \n", - "... ... ... ... ... \n", - "3834560 R-HSA-193807 pathway interacts with pathway_protein \n", - "3834561 R-HSA-1989781 pathway interacts with pathway_protein \n", - "3834562 R-HSA-211976 pathway interacts with pathway_protein \n", - "3834563 R-HSA-383280 pathway interacts with pathway_protein \n", - "3834564 R-HSA-4090294 pathway interacts with pathway_protein \n", - "\n", - "[610 rows x 12 columns]" - ] - }, - "execution_count": 11, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# IBD pathway_protein edges \n", - "ibd_pathway_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'pathway') & \n", - " (primekg_edges.tail_type == 'gene/protein') & \n", - " (primekg_edges.tail_index.isin(ibd_protein_index))],\n", - " primekg_edges[(primekg_edges.tail_type == 'pathway') & \n", - " (primekg_edges.head_type == 'gene/protein') & \n", - " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", - "\n", - "# Check dataframe\n", - "ibd_pathway_protein_edges_df" - ] - }, - { - "cell_type": "code", - "execution_count": 12, - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "array([ 62341, 62373, 62376, 62394, 62400, 62404, 62405, 62414,\n", - " 62448, 62462, 62465, 62467, 62469, 62472, 62483, 62543,\n", - " 62571, 62575, 62588, 62596, 62603, 62606, 62628, 62644,\n", - " 62651, 62691, 62692, 62697, 62702, 62711, 62717, 62733,\n", - " 62734, 62805, 62807, 62916, 62925, 62968, 62987, 62996,\n", - " 63041, 63064, 63071, 63076, 127601, 127639, 127640, 127682,\n", - " 127683, 127688, 127691, 127693, 127694, 127696, 127730, 127731,\n", - " 127733, 127791, 127797, 127815, 127835, 127856, 127858, 127866,\n", - " 127869, 127886, 127908, 127917, 127918, 127960, 127971, 127977,\n", - " 127999, 128001, 128010, 128015, 128025, 128034, 128058, 128065,\n", - " 128071, 128072, 128073, 128074, 128111, 128113, 128116, 128117,\n", - " 128137, 128138, 128139, 128158, 128165, 128176, 128191, 128198,\n", - " 128204, 128208, 128227, 128242, 128243, 128244, 128253, 128254,\n", - " 128272, 128299, 128302, 128341, 128348, 128350, 128353, 128360,\n", - " 128378, 128393, 128395, 128396, 128399, 128472, 128477, 128478,\n", - " 128479, 128480, 128481, 128482, 128483, 128484, 128486, 128487,\n", - " 128497, 128498, 128499, 128500, 128501, 128503, 128550, 128593,\n", - " 128601, 128655, 128766, 128767, 128781, 128782, 128783, 128801,\n", - " 128804, 128814, 128815, 128827, 128828, 128829, 128830, 128832,\n", - " 128835, 128838, 128846, 128851, 128852, 128878, 128978, 128979,\n", - " 128980, 128981, 128990, 129007, 129015, 129016, 129035, 129040,\n", - " 129044, 129048, 129052, 129099, 129110, 129124, 129125, 129126,\n", - " 129127, 129128, 129131, 129136, 129139, 129140, 129141, 129148,\n", - " 129155, 129167, 129181, 129183, 129190, 129195, 129196, 129197,\n", - " 129198, 129215, 129217, 129238, 129257, 129258, 129259, 129266,\n", - " 129289, 129294, 129296, 129302, 129310, 129355, 129360, 129361,\n", - " 129366])" - ] - }, - "execution_count": 12, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Get unique protein index\n", - "ibd_pathway_index = np.unique(np.concatenate([ibd_pathway_protein_edges_df[ibd_pathway_protein_edges_df.head_type == 'pathway'].head_index.unique(),\n", - " ibd_pathway_protein_edges_df[ibd_pathway_protein_edges_df.tail_type == 'pathway'].tail_index.unique()]))\n", - "ibd_pathway_index" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Pathway-Pathway Relationship" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "As well as, a set of records containing the relationships of pathway-pathway nodes." - ] - }, - { - "cell_type": "code", - "execution_count": 13, - "metadata": {}, - "outputs": [], - "source": [ - "# # # IBD pathway_pathway edges \n", - "# ibd_pathway_pathway_edges_df = pd.concat([primekg_edges[(primekg_edges.head_index.isin(ibd_pathway_index)) & \n", - "# (primekg_edges.tail_type == 'pathway')],\n", - "# primekg_edges[(primekg_edges.tail_index.isin(ibd_pathway_index)) & \n", - "# (primekg_edges.head_type == 'pathway')]])\n", - "\n", - "# # Check dataframe\n", - "# ibd_pathway_pathway_edges_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Bioprocess-Protein Relationship" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Next step is to get the records containing the relationships of biological_process-gene/protein nodes." - ] - }, - { - "cell_type": "code", - "execution_count": 14, - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
6351300112487neutrophil degranulationGO43312biological_process3333FPR2NCBI2358gene/proteininteracts withbioprocess_protein
6351346112487neutrophil degranulationGO43312biological_process5022ITGAMNCBI3684gene/proteininteracts withbioprocess_protein
6351457112487neutrophil degranulationGO43312biological_process12663SLC11A1NCBI6556gene/proteininteracts withbioprocess_protein
6351710103224platelet degranulationGO2576biological_process2057FN1NCBI2335gene/proteininteracts withbioprocess_protein
6351714103224platelet degranulationGO2576biological_process5720IGF1NCBI3479gene/proteininteracts withbioprocess_protein
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37817072111LRRK2NCBI120892gene/protein51599negative regulation of peroxidase activityGO2000469biological_processinteracts withbioprocess_protein
37817082111LRRK2NCBI120892gene/protein52358regulation of kidney sizeGO35564biological_processinteracts withbioprocess_protein
37817102111LRRK2NCBI120892gene/protein109343negative regulation of thioredoxin peroxidase ...GO1903125biological_processinteracts withbioprocess_protein
378181122105GPBAR1NCBI151306gene/protein105254cell surface bile acid receptor signaling pathwayGO38184biological_processinteracts withbioprocess_protein
378182434779NKX2-3NCBI159296gene/protein100699post-embryonic digestive tract morphogenesisGO48621biological_processinteracts withbioprocess_protein
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3880 rows × 12 columns

\n", - "
" - ], - "text/plain": [ - " head_index head_name head_source head_id \\\n", - "6351300 112487 neutrophil degranulation GO 43312 \n", - "6351346 112487 neutrophil degranulation GO 43312 \n", - "6351457 112487 neutrophil degranulation GO 43312 \n", - "6351710 103224 platelet degranulation GO 2576 \n", - "6351714 103224 platelet degranulation GO 2576 \n", - "... ... ... ... ... \n", - "3781707 2111 LRRK2 NCBI 120892 \n", - "3781708 2111 LRRK2 NCBI 120892 \n", - "3781710 2111 LRRK2 NCBI 120892 \n", - "3781811 22105 GPBAR1 NCBI 151306 \n", - "3781824 34779 NKX2-3 NCBI 159296 \n", - "\n", - " head_type tail_index \\\n", - "6351300 biological_process 3333 \n", - "6351346 biological_process 5022 \n", - "6351457 biological_process 12663 \n", - "6351710 biological_process 2057 \n", - "6351714 biological_process 5720 \n", - "... ... ... \n", - "3781707 gene/protein 51599 \n", - "3781708 gene/protein 52358 \n", - "3781710 gene/protein 109343 \n", - "3781811 gene/protein 105254 \n", - "3781824 gene/protein 100699 \n", - "\n", - " tail_name tail_source \\\n", - "6351300 FPR2 NCBI \n", - "6351346 ITGAM NCBI \n", - "6351457 SLC11A1 NCBI \n", - "6351710 FN1 NCBI \n", - "6351714 IGF1 NCBI \n", - "... ... ... \n", - "3781707 negative regulation of peroxidase activity GO \n", - "3781708 regulation of kidney size GO \n", - "3781710 negative regulation of thioredoxin peroxidase ... GO \n", - "3781811 cell surface bile acid receptor signaling pathway GO \n", - "3781824 post-embryonic digestive tract morphogenesis GO \n", - "\n", - " tail_id tail_type display_relation relation \n", - "6351300 2358 gene/protein interacts with bioprocess_protein \n", - "6351346 3684 gene/protein interacts with bioprocess_protein \n", - "6351457 6556 gene/protein interacts with bioprocess_protein \n", - "6351710 2335 gene/protein interacts with bioprocess_protein \n", - "6351714 3479 gene/protein interacts with bioprocess_protein \n", - "... ... ... ... ... \n", - "3781707 2000469 biological_process interacts with bioprocess_protein \n", - "3781708 35564 biological_process interacts with bioprocess_protein \n", - "3781710 1903125 biological_process interacts with bioprocess_protein \n", - "3781811 38184 biological_process interacts with bioprocess_protein \n", - "3781824 48621 biological_process interacts with bioprocess_protein \n", - "\n", - "[3880 rows x 12 columns]" - ] - }, - "execution_count": 14, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# IBD bioprocess_protein edges \n", - "ibd_bioprocess_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'biological_process') & \n", - " (primekg_edges.tail_type == 'gene/protein') & \n", - " (primekg_edges.tail_index.isin(ibd_protein_index))],\n", - " primekg_edges[(primekg_edges.tail_type == 'biological_process') & \n", - " (primekg_edges.head_type == 'gene/protein') & \n", - " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", - "\n", - "# Check dataframe\n", - "ibd_bioprocess_protein_edges_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### MolFunc-Protein Relationship" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Here, we would like to get biological_process-gene/protein relationships." - ] - }, - { - "cell_type": "code", - "execution_count": 15, - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
619836654290enzyme bindingGO19899molecular_function2057FN1NCBI2335gene/proteininteracts withmolfunc_protein
619844254290enzyme bindingGO19899molecular_function989PPARGNCBI5468gene/proteininteracts withmolfunc_protein
619863454290enzyme bindingGO19899molecular_function6229NOD2NCBI64127gene/proteininteracts withmolfunc_protein
619870854671protease bindingGO2020molecular_function2057FN1NCBI2335gene/proteininteracts withmolfunc_protein
619874754671protease bindingGO2020molecular_function2329TNFNCBI7124gene/proteininteracts withmolfunc_protein
.......................................
35535336229NOD2NCBI64127gene/protein122117muramyl dipeptide bindingGO32500molecular_functioninteracts withmolfunc_protein
35537702111LRRK2NCBI120892gene/protein115199GTP-dependent protein kinase activityGO34211molecular_functioninteracts withmolfunc_protein
35537712111LRRK2NCBI120892gene/protein118105beta-catenin destruction complex bindingGO1904713molecular_functioninteracts withmolfunc_protein
35537732111LRRK2NCBI120892gene/protein119847peroxidase inhibitor activityGO36479molecular_functioninteracts withmolfunc_protein
355383222105GPBAR1NCBI151306gene/protein116806G protein-coupled bile acid receptor activityGO38182molecular_functioninteracts withmolfunc_protein
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848 rows × 12 columns

\n", - "
" - ], - "text/plain": [ - " head_index head_name head_source head_id head_type \\\n", - "6198366 54290 enzyme binding GO 19899 molecular_function \n", - "6198442 54290 enzyme binding GO 19899 molecular_function \n", - "6198634 54290 enzyme binding GO 19899 molecular_function \n", - "6198708 54671 protease binding GO 2020 molecular_function \n", - "6198747 54671 protease binding GO 2020 molecular_function \n", - "... ... ... ... ... ... \n", - "3553533 6229 NOD2 NCBI 64127 gene/protein \n", - "3553770 2111 LRRK2 NCBI 120892 gene/protein \n", - "3553771 2111 LRRK2 NCBI 120892 gene/protein \n", - "3553773 2111 LRRK2 NCBI 120892 gene/protein \n", - "3553832 22105 GPBAR1 NCBI 151306 gene/protein \n", - "\n", - " tail_index tail_name \\\n", - "6198366 2057 FN1 \n", - "6198442 989 PPARG \n", - "6198634 6229 NOD2 \n", - "6198708 2057 FN1 \n", - "6198747 2329 TNF \n", - "... ... ... \n", - "3553533 122117 muramyl dipeptide binding \n", - "3553770 115199 GTP-dependent protein kinase activity \n", - "3553771 118105 beta-catenin destruction complex binding \n", - "3553773 119847 peroxidase inhibitor activity \n", - "3553832 116806 G protein-coupled bile acid receptor activity \n", - "\n", - " tail_source tail_id tail_type display_relation \\\n", - "6198366 NCBI 2335 gene/protein interacts with \n", - "6198442 NCBI 5468 gene/protein interacts with \n", - "6198634 NCBI 64127 gene/protein interacts with \n", - "6198708 NCBI 2335 gene/protein interacts with \n", - "6198747 NCBI 7124 gene/protein interacts with \n", - "... ... ... ... ... \n", - "3553533 GO 32500 molecular_function interacts with \n", - "3553770 GO 34211 molecular_function interacts with \n", - "3553771 GO 1904713 molecular_function interacts with \n", - "3553773 GO 36479 molecular_function interacts with \n", - "3553832 GO 38182 molecular_function interacts with \n", - "\n", - " relation \n", - "6198366 molfunc_protein \n", - "6198442 molfunc_protein \n", - "6198634 molfunc_protein \n", - "6198708 molfunc_protein \n", - "6198747 molfunc_protein \n", - "... ... \n", - "3553533 molfunc_protein \n", - "3553770 molfunc_protein \n", - "3553771 molfunc_protein \n", - "3553773 molfunc_protein \n", - "3553832 molfunc_protein \n", - "\n", - "[848 rows x 12 columns]" - ] - }, - "execution_count": 15, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# IBD molfunc_protein edges \n", - "ibd_molfunc_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'molecular_function') & \n", - " (primekg_edges.tail_type == 'gene/protein') & \n", - " (primekg_edges.tail_index.isin(ibd_protein_index))],\n", - " primekg_edges[(primekg_edges.tail_type == 'molecular_function') & \n", - " (primekg_edges.head_type == 'gene/protein') & \n", - " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", - "\n", - "# Check dataframe\n", - "ibd_molfunc_protein_edges_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### CellComp-Protein Relationship" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Finally, we are getting the records containing the relationships of cellular_component-gene/protein nodes." - ] - }, - { - "cell_type": "code", - "execution_count": 16, - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelation
6268120124245extracellular spaceGO5615cellular_component2384CRPNCBI1401gene/proteininteracts withcellcomp_protein
6268231124245extracellular spaceGO5615cellular_component2057FN1NCBI2335gene/proteininteracts withcellcomp_protein
6268290124245extracellular spaceGO5615cellular_component7083HLA-DRB1NCBI3123gene/proteininteracts withcellcomp_protein
6268329124245extracellular spaceGO5615cellular_component3495IFNGNCBI3458gene/proteininteracts withcellcomp_protein
6268331124245extracellular spaceGO5615cellular_component5720IGF1NCBI3479gene/proteininteracts withcellcomp_protein
.......................................
36363606661ATG16L1NCBI55054gene/protein125634phagophore assembly site membraneGO34045cellular_componentinteracts withcellcomp_protein
36364722111LRRK2NCBI120892gene/protein127370amphisomeGO44753cellular_componentinteracts withcellcomp_protein
36372116661ATG16L1NCBI55054gene/protein126444vacuole-isolation membrane contact siteGO120095cellular_componentinteracts withcellcomp_protein
36372342111LRRK2NCBI120892gene/protein126938cytoplasmic side of mitochondrial outer membraneGO32473cellular_componentinteracts withcellcomp_protein
36373282111LRRK2NCBI120892gene/protein125942caveola neckGO99400cellular_componentinteracts withcellcomp_protein
\n", - "

710 rows × 12 columns

\n", - "
" - ], - "text/plain": [ - " head_index head_name head_source head_id \\\n", - "6268120 124245 extracellular space GO 5615 \n", - "6268231 124245 extracellular space GO 5615 \n", - "6268290 124245 extracellular space GO 5615 \n", - "6268329 124245 extracellular space GO 5615 \n", - "6268331 124245 extracellular space GO 5615 \n", - "... ... ... ... ... \n", - "3636360 6661 ATG16L1 NCBI 55054 \n", - "3636472 2111 LRRK2 NCBI 120892 \n", - "3637211 6661 ATG16L1 NCBI 55054 \n", - "3637234 2111 LRRK2 NCBI 120892 \n", - "3637328 2111 LRRK2 NCBI 120892 \n", - "\n", - " head_type tail_index \\\n", - "6268120 cellular_component 2384 \n", - "6268231 cellular_component 2057 \n", - "6268290 cellular_component 7083 \n", - "6268329 cellular_component 3495 \n", - "6268331 cellular_component 5720 \n", - "... ... ... \n", - "3636360 gene/protein 125634 \n", - "3636472 gene/protein 127370 \n", - "3637211 gene/protein 126444 \n", - "3637234 gene/protein 126938 \n", - "3637328 gene/protein 125942 \n", - "\n", - " tail_name tail_source tail_id \\\n", - "6268120 CRP NCBI 1401 \n", - "6268231 FN1 NCBI 2335 \n", - "6268290 HLA-DRB1 NCBI 3123 \n", - "6268329 IFNG NCBI 3458 \n", - "6268331 IGF1 NCBI 3479 \n", - "... ... ... ... \n", - "3636360 phagophore assembly site membrane GO 34045 \n", - "3636472 amphisome GO 44753 \n", - "3637211 vacuole-isolation membrane contact site GO 120095 \n", - "3637234 cytoplasmic side of mitochondrial outer membrane GO 32473 \n", - "3637328 caveola neck GO 99400 \n", - "\n", - " tail_type display_relation relation \n", - "6268120 gene/protein interacts with cellcomp_protein \n", - "6268231 gene/protein interacts with cellcomp_protein \n", - "6268290 gene/protein interacts with cellcomp_protein \n", - "6268329 gene/protein interacts with cellcomp_protein \n", - "6268331 gene/protein interacts with cellcomp_protein \n", - "... ... ... ... \n", - "3636360 cellular_component interacts with cellcomp_protein \n", - "3636472 cellular_component interacts with cellcomp_protein \n", - "3637211 cellular_component interacts with cellcomp_protein \n", - "3637234 cellular_component interacts with cellcomp_protein \n", - "3637328 cellular_component interacts with cellcomp_protein \n", - "\n", - "[710 rows x 12 columns]" - ] - }, - "execution_count": 16, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# IBD molfunc_protein edges \n", - "ibd_cellcomp_protein_edges_df = pd.concat([primekg_edges[(primekg_edges.head_type == 'cellular_component') & \n", - " (primekg_edges.tail_type == 'gene/protein') & \n", - " (primekg_edges.tail_index.isin(ibd_protein_index))],\n", - " primekg_edges[(primekg_edges.tail_type == 'cellular_component') & \n", - " (primekg_edges.head_type == 'gene/protein') & \n", - " (primekg_edges.head_index.isin(ibd_protein_index))]])\n", - "\n", - "# Check dataframe\n", - "ibd_cellcomp_protein_edges_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Merge all dataframes" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Once we have all of particular type of edges, we can merge them into a single dataframe representing a subgraph of IBD inferred from PrimeKG." - ] - }, - { - "cell_type": "code", - "execution_count": 17, - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelationedge_type
037784Crohn diseaseMONDO_grouped5011_5535disease2384CRPNCBI1401gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
183770Crohn's colitisMONDO5532disease2384CRPNCBI1401gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
237784Crohn diseaseMONDO_grouped5011_5535disease3088DNMT3ANCBI1788gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
383770Crohn's colitisMONDO5532disease3088DNMT3ANCBI1788gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
437784Crohn diseaseMONDO_grouped5011_5535disease2057FN1NCBI2335gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)
..........................................
70636661ATG16L1NCBI55054gene/protein125634phagophore assembly site membraneGO34045cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
70642111LRRK2NCBI120892gene/protein127370amphisomeGO44753cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
70656661ATG16L1NCBI55054gene/protein126444vacuole-isolation membrane contact siteGO120095cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
70662111LRRK2NCBI120892gene/protein126938cytoplasmic side of mitochondrial outer membraneGO32473cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
70672111LRRK2NCBI120892gene/protein125942caveola neckGO99400cellular_componentinteracts withcellcomp_protein(gene/protein, interacts with, cellular_compon...
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7068 rows × 13 columns

\n", - "
" - ], - "text/plain": [ - " head_index head_name head_source head_id head_type \\\n", - "0 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", - "1 83770 Crohn's colitis MONDO 5532 disease \n", - "2 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", - "3 83770 Crohn's colitis MONDO 5532 disease \n", - "4 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", - "... ... ... ... ... ... \n", - "7063 6661 ATG16L1 NCBI 55054 gene/protein \n", - "7064 2111 LRRK2 NCBI 120892 gene/protein \n", - "7065 6661 ATG16L1 NCBI 55054 gene/protein \n", - "7066 2111 LRRK2 NCBI 120892 gene/protein \n", - "7067 2111 LRRK2 NCBI 120892 gene/protein \n", - "\n", - " tail_index tail_name \\\n", - "0 2384 CRP \n", - "1 2384 CRP \n", - "2 3088 DNMT3A \n", - "3 3088 DNMT3A \n", - "4 2057 FN1 \n", - "... ... ... \n", - "7063 125634 phagophore assembly site membrane \n", - "7064 127370 amphisome \n", - "7065 126444 vacuole-isolation membrane contact site \n", - "7066 126938 cytoplasmic side of mitochondrial outer membrane \n", - "7067 125942 caveola neck \n", - "\n", - " tail_source tail_id tail_type display_relation \\\n", - "0 NCBI 1401 gene/protein associated with \n", - "1 NCBI 1401 gene/protein associated with \n", - "2 NCBI 1788 gene/protein associated with \n", - "3 NCBI 1788 gene/protein associated with \n", - "4 NCBI 2335 gene/protein associated with \n", - "... ... ... ... ... \n", - "7063 GO 34045 cellular_component interacts with \n", - "7064 GO 44753 cellular_component interacts with \n", - "7065 GO 120095 cellular_component interacts with \n", - "7066 GO 32473 cellular_component interacts with \n", - "7067 GO 99400 cellular_component interacts with \n", - "\n", - " relation edge_type \n", - "0 disease_protein (disease, associated with, gene/protein) \n", - "1 disease_protein (disease, associated with, gene/protein) \n", - "2 disease_protein (disease, associated with, gene/protein) \n", - "3 disease_protein (disease, associated with, gene/protein) \n", - "4 disease_protein (disease, associated with, gene/protein) \n", - "... ... ... \n", - "7063 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", - "7064 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", - "7065 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", - "7066 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", - "7067 cellcomp_protein (gene/protein, interacts with, cellular_compon... \n", - "\n", - "[7068 rows x 13 columns]" - ] - }, - "execution_count": 17, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# PrimeKG edges related to IBD\n", - "primekg_ibd_edges_df = pd.concat([ibd_disease_protein_edges_df,\n", - " # ibd_disease_disease_edges_df,\n", - " # ibd_protein_protein_edges_df,\n", - " ibd_drug_protein_edges_df,\n", - " ibd_pathway_protein_edges_df,\n", - " # ibd_pathway_pathway_edges_df,\n", - " ibd_bioprocess_protein_edges_df,\n", - " ibd_molfunc_protein_edges_df,\n", - " ibd_cellcomp_protein_edges_df])\n", - "primekg_ibd_edges_df[\"edge_type\"] = primekg_ibd_edges_df.apply(lambda x: (x.head_type, x.display_relation, x.tail_type), axis=1)\n", - "primekg_ibd_edges_df.drop_duplicates(subset=['head_index', 'tail_index'], inplace=True)\n", - "primekg_ibd_edges_df.reset_index(drop=True, inplace=True)\n", - "primekg_ibd_edges_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "We can get a dataframe of nodes based on the above edge dataframe as follows:" - ] - }, - { - "cell_type": "code", - "execution_count": 18, - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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node_indexnode_namenode_sourcenode_idnode_type
144144SMAD3NCBI4088gene/protein
729729STAT3NCBI6774gene/protein
989989PPARGNCBI5468gene/protein
11221122PPARANCBI5465gene/protein
14801480ADIPOQNCBI9370gene/protein
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129310129310Potential therapeutics for SARSREACTOMER-HSA-9679191pathway
129355129355Detoxification of Reactive Oxygen SpeciesREACTOMER-HSA-3299685pathway
129360129360IRAK2 mediated activation of TAK1 complex upon...REACTOMER-HSA-975163pathway
129361129361TRAF6 mediated IRF7 activation in TLR7/8 or 9 ...REACTOMER-HSA-975110pathway
129366129366Antigen Presentation: Folding, assembly and pe...REACTOMER-HSA-983170pathway
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2079 rows × 5 columns

\n", - "
" - ], - "text/plain": [ - " node_index node_name \\\n", - "144 144 SMAD3 \n", - "729 729 STAT3 \n", - "989 989 PPARG \n", - "1122 1122 PPARA \n", - "1480 1480 ADIPOQ \n", - "... ... ... \n", - "129310 129310 Potential therapeutics for SARS \n", - "129355 129355 Detoxification of Reactive Oxygen Species \n", - "129360 129360 IRAK2 mediated activation of TAK1 complex upon... \n", - "129361 129361 TRAF6 mediated IRF7 activation in TLR7/8 or 9 ... \n", - "129366 129366 Antigen Presentation: Folding, assembly and pe... \n", - "\n", - " node_source node_id node_type \n", - "144 NCBI 4088 gene/protein \n", - "729 NCBI 6774 gene/protein \n", - "989 NCBI 5468 gene/protein \n", - "1122 NCBI 5465 gene/protein \n", - "1480 NCBI 9370 gene/protein \n", - "... ... ... ... \n", - "129310 REACTOME R-HSA-9679191 pathway \n", - "129355 REACTOME R-HSA-3299685 pathway \n", - "129360 REACTOME R-HSA-975163 pathway \n", - "129361 REACTOME R-HSA-975110 pathway \n", - "129366 REACTOME R-HSA-983170 pathway \n", - "\n", - "[2079 rows x 5 columns]" - ] - }, - "execution_count": 18, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# PrimeKG nodes related to IBD\n", - "primekg_ibd_nodes_df = primekg_nodes[primekg_nodes.index.isin(np.unique(np.hstack([primekg_ibd_edges_df.head_index.unique(), \n", - " primekg_ibd_edges_df.tail_index.unique()])))]\n", - "primekg_ibd_nodes_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "We can store the nodes and edges related to IBD in a parquet file for future use." - ] - }, - { - "cell_type": "code", - "execution_count": 20, - "metadata": {}, - "outputs": [], - "source": [ - "# Store the IBD-related nodes and edges\n", - "local_dir = '../../data/primekg_ibd/'\n", - "if not os.path.exists(local_dir):\n", - " os.makedirs(local_dir)\n", - "primekg_ibd_nodes_df.to_parquet(os.path.join(local_dir, 'primekg_ibd_nodes.parquet'), compression='gzip', index=False)\n", - "primekg_ibd_edges_df.to_parquet(os.path.join(local_dir, 'primekg_ibd_edges.parquet'), compression='gzip', index=False)" - ] - }, - { - "cell_type": "code", - "execution_count": 21, - "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "Number of IBD-related nodes: 2079\n", - "Number of IBD-related edges: 7068\n" - ] - } - ], - "source": [ - "# Statistics over the IBD-related nodes and edges\n", - "print(f\"Number of IBD-related nodes: {primekg_ibd_nodes_df.shape[0]}\")\n", - "print(f\"Number of IBD-related edges: {primekg_ibd_edges_df.shape[0]}\")" - ] - }, - { - "cell_type": "code", - "execution_count": 22, - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "node_type\n", - "biological_process 1172\n", - "cellular_component 146\n", - "disease 3\n", - "drug 276\n", - "gene/protein 51\n", - "molecular_function 222\n", - "pathway 209\n", - "dtype: int64" - ] - }, - "execution_count": 22, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Count the number of nodes by node type\n", - "primekg_ibd_nodes_df.groupby('node_type').size()" - ] - }, - { - "cell_type": "code", - "execution_count": 23, - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "relation display_relation\n", - "bioprocess_protein interacts with 3880\n", - "cellcomp_protein interacts with 710\n", - "disease_protein associated with 290\n", - "drug_protein enzyme 14\n", - " target 538\n", - " transporter 178\n", - "molfunc_protein interacts with 848\n", - "pathway_protein interacts with 610\n", - "dtype: int64" - ] - }, - "execution_count": 23, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Count the number of edges by relation and display_relation\n", - "primekg_ibd_edges_df.groupby(['relation','display_relation']).size()" - ] - }, - { - "cell_type": "code", - "execution_count": 24, - "metadata": {}, - "outputs": [ - { - "data": { - "text/plain": [ - "edge_type\n", - "(biological_process, interacts with, gene/protein) 1940\n", - "(cellular_component, interacts with, gene/protein) 355\n", - "(disease, associated with, gene/protein) 145\n", - "(drug, enzyme, gene/protein) 7\n", - "(drug, target, gene/protein) 269\n", - "(drug, transporter, gene/protein) 89\n", - "(gene/protein, associated with, disease) 145\n", - "(gene/protein, enzyme, drug) 7\n", - "(gene/protein, interacts with, biological_process) 1940\n", - "(gene/protein, interacts with, cellular_component) 355\n", - "(gene/protein, interacts with, molecular_function) 424\n", - "(gene/protein, interacts with, pathway) 305\n", - "(gene/protein, target, drug) 269\n", - "(gene/protein, transporter, drug) 89\n", - "(molecular_function, interacts with, gene/protein) 424\n", - "(pathway, interacts with, gene/protein) 305\n", - "dtype: int64" - ] - }, - "execution_count": 24, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Count the number of edges by edge type\n", - "primekg_ibd_edges_df.groupby(['edge_type']).size()" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "### Enrichment (using textual as of now)" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "From this point onwards, we will use the pre-processed IBD-related nodes and edges to create a set of graph formats.\n", - "\n", - "Before that, we should perform enrichment and embedding over the IBD-related nodes and edges.\n", - "\n", - "As of now, we will conduct a textual enrichment over the records.\n", - "\n", - "Since StarQA provide most of information of the nodes, we will use StarkQA to get the information of the nodes related to IBD." - ] - }, - { - "cell_type": "code", - "execution_count": 26, - "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "Loading StarkQAPrimeKG dataset...\n", - "../../data/starkqa_primekg/qa/prime/stark_qa/stark_qa.csv already exists. Loading the data from the local directory.\n", - "Loading StarkQAPrimeKG embeddings...\n" - ] - } - ], - "source": [ - "# Define starkqa primekg data by providing a local directory where the data is stored\n", - "starkqa_data = StarkQAPrimeKG(local_dir=\"../../data/starkqa_primekg/\")\n", - "\n", - "# Invoke a method to load the data\n", - "starkqa_data.load_data()\n", - "\n", - "# Get the StarkQAPrimeKG data, which are the QA pairs, split indices, and the node information\n", - "# starkqa_df = starkqa_data.get_starkqa()\n", - "starkqa_node_info = starkqa_data.get_starkqa_node_info()" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Note that not all nodes in the StarkQA-PrimeKG have additional information. \n", - "\n", - "For this case, we provide a basic text enrichment for the nodes by simply specifying their node name and type." - ] - }, - { - "cell_type": "code", - "execution_count": 27, - "metadata": {}, - "outputs": [], - "source": [ - "def do_enrichment_text(data, starkqa_node_info):\n", - " \"\"\"\n", - " Enrich the node with additional textual information from BioBridge and StarkQA.\n", - "\n", - " Args:\n", - " data (dict): The node data from PrimeKG\n", - " starkqa_node_info (dict): The node information from StarkQA-PrimeKG\n", - " \"\"\"\n", - " # Basic textual enrichment of the node\n", - " enriched_node = f\"{data['node_name']} belongs to {data['node_type']} category. \"\n", - "\n", - " # Only enrich the node if the node type is gene/protein, drug, disease, or pathway, which\n", - " # has additional information in the node_info of StarkQA-PrimeKG\n", - " added_info = ''\n", - " if data['node_type'] == 'gene/protein':\n", - " added_info = starkqa_node_info['details']['summary'] if 'summary' in starkqa_node_info['details'] else ''\n", - " elif data['node_type'] == 'drug':\n", - " added_info = ' '.join([str(starkqa_node_info['details']['description']).replace('nan', ''),\n", - " str(starkqa_node_info['details']['mechanism_of_action']).replace('nan', ''),\n", - " str(starkqa_node_info['details']['protein_binding']).replace('nan', ''),\n", - " str(starkqa_node_info['details']['pharmacodynamics']).replace('nan', ''),\n", - " str(starkqa_node_info['details']['indication']).replace('nan', '')])\n", - " elif data['node_type'] == 'disease':\n", - " added_info = ' '.join([str(starkqa_node_info['details']['mondo_definition']).replace('nan', ''),\n", - " str(starkqa_node_info['details']['mayo_symptoms']).replace('nan', ''),\n", - " str(starkqa_node_info['details']['mayo_causes']).replace('nan', '')])\n", - " elif data['node_type'] == 'pathway':\n", - " added_info += f\"This pathway found in {starkqa_node_info['details']['speciesName']}. \" + ' '.join([x['text'] for x in starkqa_node_info['details']['summation']]) if 'details' in starkqa_node_info else ''\n", - "\n", - " # Append the additional information for enrichment\n", - " enriched_node += added_info\n", - " return enriched_node" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "By using the above function, we can enrich the node information from PrimeKG with additional information from StarkQA-PrimeKG as shown below:" - ] - }, - { - "cell_type": "code", - "execution_count": 28, - "metadata": {}, - "outputs": [ - { - "name": "stderr", - "output_type": "stream", - "text": [ - "/tmp/ipykernel_1377/2873064541.py:3: SettingWithCopyWarning: \n", - "A value is trying to be set on a copy of a slice from a DataFrame.\n", - "Try using .loc[row_indexer,col_indexer] = value instead\n", - "\n", - "See the caveats in the documentation: https://pandas.pydata.org/pandas-docs/stable/user_guide/indexing.html#returning-a-view-versus-a-copy\n", - " primekg_ibd_nodes_df['enriched_node'] = text_enriched_nodes\n" - ] - }, - { - "data": { - "text/html": [ - "
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node_indexnode_namenode_sourcenode_idnode_typeenriched_node
144144SMAD3NCBI4088gene/proteinSMAD3 belongs to gene/protein category. The SM...
729729STAT3NCBI6774gene/proteinSTAT3 belongs to gene/protein category. The pr...
989989PPARGNCBI5468gene/proteinPPARG belongs to gene/protein category. This g...
11221122PPARANCBI5465gene/proteinPPARA belongs to gene/protein category. Peroxi...
14801480ADIPOQNCBI9370gene/proteinADIPOQ belongs to gene/protein category. This ...
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129310129310Potential therapeutics for SARSREACTOMER-HSA-9679191pathwayPotential therapeutics for SARS belongs to pat...
129355129355Detoxification of Reactive Oxygen SpeciesREACTOMER-HSA-3299685pathwayDetoxification of Reactive Oxygen Species belo...
129360129360IRAK2 mediated activation of TAK1 complex upon...REACTOMER-HSA-975163pathwayIRAK2 mediated activation of TAK1 complex upon...
129361129361TRAF6 mediated IRF7 activation in TLR7/8 or 9 ...REACTOMER-HSA-975110pathwayTRAF6 mediated IRF7 activation in TLR7/8 or 9 ...
129366129366Antigen Presentation: Folding, assembly and pe...REACTOMER-HSA-983170pathwayAntigen Presentation: Folding, assembly and pe...
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2079 rows × 6 columns

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" - ], - "text/plain": [ - " node_index node_name \\\n", - "144 144 SMAD3 \n", - "729 729 STAT3 \n", - "989 989 PPARG \n", - "1122 1122 PPARA \n", - "1480 1480 ADIPOQ \n", - "... ... ... \n", - "129310 129310 Potential therapeutics for SARS \n", - "129355 129355 Detoxification of Reactive Oxygen Species \n", - "129360 129360 IRAK2 mediated activation of TAK1 complex upon... \n", - "129361 129361 TRAF6 mediated IRF7 activation in TLR7/8 or 9 ... \n", - "129366 129366 Antigen Presentation: Folding, assembly and pe... \n", - "\n", - " node_source node_id node_type \\\n", - "144 NCBI 4088 gene/protein \n", - "729 NCBI 6774 gene/protein \n", - "989 NCBI 5468 gene/protein \n", - "1122 NCBI 5465 gene/protein \n", - "1480 NCBI 9370 gene/protein \n", - "... ... ... ... \n", - "129310 REACTOME R-HSA-9679191 pathway \n", - "129355 REACTOME R-HSA-3299685 pathway \n", - "129360 REACTOME R-HSA-975163 pathway \n", - "129361 REACTOME R-HSA-975110 pathway \n", - "129366 REACTOME R-HSA-983170 pathway \n", - "\n", - " enriched_node \n", - "144 SMAD3 belongs to gene/protein category. The SM... \n", - "729 STAT3 belongs to gene/protein category. The pr... \n", - "989 PPARG belongs to gene/protein category. This g... \n", - "1122 PPARA belongs to gene/protein category. Peroxi... \n", - "1480 ADIPOQ belongs to gene/protein category. This ... \n", - "... ... \n", - "129310 Potential therapeutics for SARS belongs to pat... \n", - "129355 Detoxification of Reactive Oxygen Species belo... \n", - "129360 IRAK2 mediated activation of TAK1 complex upon... \n", - "129361 TRAF6 mediated IRF7 activation in TLR7/8 or 9 ... \n", - "129366 Antigen Presentation: Folding, assembly and pe... \n", - "\n", - "[2079 rows x 6 columns]" - ] - }, - "execution_count": 28, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Perform node enrichment for each row in primekg_nodes\n", - "text_enriched_nodes = primekg_ibd_nodes_df.apply(lambda x: do_enrichment_text(x, starkqa_node_info[x['node_index']]), axis=1).tolist()\n", - "primekg_ibd_nodes_df['enriched_node'] = text_enriched_nodes\n", - "primekg_ibd_nodes_df" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Subsequently, we can perform similar textual enrichment for the edges in PrimeKG.\n", - "\n", - "Since StarkQA only provides node information, we can only enrich the edges with basic information of the triples in combination with the head and tail nodes." - ] - }, - { - "cell_type": "code", - "execution_count": 29, - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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head_indexhead_namehead_sourcehead_idhead_typetail_indextail_nametail_sourcetail_idtail_typedisplay_relationrelationedge_typeenriched_edge
037784Crohn diseaseMONDO_grouped5011_5535disease2384CRPNCBI1401gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn disease (disease) has a direct relations...
183770Crohn's colitisMONDO5532disease2384CRPNCBI1401gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn's colitis (disease) has a direct relatio...
237784Crohn diseaseMONDO_grouped5011_5535disease3088DNMT3ANCBI1788gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn disease (disease) has a direct relations...
383770Crohn's colitisMONDO5532disease3088DNMT3ANCBI1788gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn's colitis (disease) has a direct relatio...
437784Crohn diseaseMONDO_grouped5011_5535disease2057FN1NCBI2335gene/proteinassociated withdisease_protein(disease, associated with, gene/protein)Crohn disease (disease) has a direct relations...
\n", - "
" - ], - "text/plain": [ - " head_index head_name head_source head_id head_type \\\n", - "0 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", - "1 83770 Crohn's colitis MONDO 5532 disease \n", - "2 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", - "3 83770 Crohn's colitis MONDO 5532 disease \n", - "4 37784 Crohn disease MONDO_grouped 5011_5535 disease \n", - "\n", - " tail_index tail_name tail_source tail_id tail_type display_relation \\\n", - "0 2384 CRP NCBI 1401 gene/protein associated with \n", - "1 2384 CRP NCBI 1401 gene/protein associated with \n", - "2 3088 DNMT3A NCBI 1788 gene/protein associated with \n", - "3 3088 DNMT3A NCBI 1788 gene/protein associated with \n", - "4 2057 FN1 NCBI 2335 gene/protein associated with \n", - "\n", - " relation edge_type \\\n", - "0 disease_protein (disease, associated with, gene/protein) \n", - "1 disease_protein (disease, associated with, gene/protein) \n", - "2 disease_protein (disease, associated with, gene/protein) \n", - "3 disease_protein (disease, associated with, gene/protein) \n", - "4 disease_protein (disease, associated with, gene/protein) \n", - "\n", - " enriched_edge \n", - "0 Crohn disease (disease) has a direct relations... \n", - "1 Crohn's colitis (disease) has a direct relatio... \n", - "2 Crohn disease (disease) has a direct relations... \n", - "3 Crohn's colitis (disease) has a direct relatio... \n", - "4 Crohn disease (disease) has a direct relations... " - ] - }, - "execution_count": 29, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Perform textual enrichment over the edges by simply concatenating the head and tail nodes with the relation followed by the enriched node information\n", - "text_enriched_edges = primekg_ibd_edges_df.apply(lambda x: f\"{x['head_name']} ({x['head_type']}) has a direct relationship of {x['relation']}:{x['display_relation']} with {x['tail_name']} ({x['tail_type']}).\", axis=1).tolist()\n", - "primekg_ibd_edges_df['enriched_edge'] = text_enriched_edges\n", - "primekg_ibd_edges_df.head()" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "### Embeddings (using textual embedding as of now)" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "We are going to perform embedding using the enriched nodes and edges by leveraging `EmbeddingWithOllama` class.\n", - "\n", - "For this purpose, we will use `nomic-embed-text`." - ] - }, - { - "cell_type": "code", - "execution_count": 30, - "metadata": {}, - "outputs": [ - { - "ename": "ValueError", - "evalue": "Error: Failed to connect to Ollama. Please check that Ollama is downloaded, running and accessible. https://ollama.com/download and restarted Ollama server.", - "output_type": "error", - "traceback": [ - "\u001b[0;31m---------------------------------------------------------------------------\u001b[0m", - "\u001b[0;31mConnectionError\u001b[0m Traceback (most recent call last)", - "File \u001b[0;32m~/FORK-AIAgents4Pharma/AIAgents4Pharma/notebook/../aiagents4pharma/talk2knowledgegraphs/utils/embeddings/ollama.py:40\u001b[0m, in \u001b[0;36mEmbeddingWithOllama.__setup\u001b[0;34m(self, model_name)\u001b[0m\n\u001b[1;32m 39\u001b[0m \u001b[38;5;28;01mtry\u001b[39;00m:\n\u001b[0;32m---> 40\u001b[0m models_list \u001b[38;5;241m=\u001b[39m \u001b[43mollama\u001b[49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mlist\u001b[49m\u001b[43m(\u001b[49m\u001b[43m)\u001b[49m[\u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mmodels\u001b[39m\u001b[38;5;124m\"\u001b[39m]\n\u001b[1;32m 41\u001b[0m \u001b[38;5;28;01mif\u001b[39;00m model_name \u001b[38;5;129;01mnot\u001b[39;00m \u001b[38;5;129;01min\u001b[39;00m [m[\u001b[38;5;124m'\u001b[39m\u001b[38;5;124mmodel\u001b[39m\u001b[38;5;124m'\u001b[39m]\u001b[38;5;241m.\u001b[39mreplace(\u001b[38;5;124m\"\u001b[39m\u001b[38;5;124m:latest\u001b[39m\u001b[38;5;124m\"\u001b[39m, \u001b[38;5;124m\"\u001b[39m\u001b[38;5;124m\"\u001b[39m) \u001b[38;5;28;01mfor\u001b[39;00m m \u001b[38;5;129;01min\u001b[39;00m models_list]:\n", - "File \u001b[0;32m~/miniconda3/envs/py311/lib/python3.11/site-packages/ollama/_client.py:567\u001b[0m, in \u001b[0;36mClient.list\u001b[0;34m(self)\u001b[0m\n\u001b[1;32m 566\u001b[0m \u001b[38;5;28;01mdef\u001b[39;00m\u001b[38;5;250m \u001b[39m\u001b[38;5;21mlist\u001b[39m(\u001b[38;5;28mself\u001b[39m) \u001b[38;5;241m-\u001b[39m\u001b[38;5;241m>\u001b[39m ListResponse:\n\u001b[0;32m--> 567\u001b[0m \u001b[38;5;28;01mreturn\u001b[39;00m \u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43m_request\u001b[49m\u001b[43m(\u001b[49m\n\u001b[1;32m 568\u001b[0m \u001b[43m \u001b[49m\u001b[43mListResponse\u001b[49m\u001b[43m,\u001b[49m\n\u001b[1;32m 569\u001b[0m \u001b[43m \u001b[49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[38;5;124;43mGET\u001b[39;49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[43m,\u001b[49m\n\u001b[1;32m 570\u001b[0m \u001b[43m \u001b[49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[38;5;124;43m/api/tags\u001b[39;49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[43m,\u001b[49m\n\u001b[1;32m 571\u001b[0m \u001b[43m \u001b[49m\u001b[43m)\u001b[49m\n", - "File \u001b[0;32m~/miniconda3/envs/py311/lib/python3.11/site-packages/ollama/_client.py:178\u001b[0m, in \u001b[0;36mClient._request\u001b[0;34m(self, cls, stream, *args, **kwargs)\u001b[0m\n\u001b[1;32m 176\u001b[0m \u001b[38;5;28;01mreturn\u001b[39;00m inner()\n\u001b[0;32m--> 178\u001b[0m \u001b[38;5;28;01mreturn\u001b[39;00m \u001b[38;5;28mcls\u001b[39m(\u001b[38;5;241m*\u001b[39m\u001b[38;5;241m*\u001b[39m\u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43m_request_raw\u001b[49m\u001b[43m(\u001b[49m\u001b[38;5;241;43m*\u001b[39;49m\u001b[43margs\u001b[49m\u001b[43m,\u001b[49m\u001b[43m \u001b[49m\u001b[38;5;241;43m*\u001b[39;49m\u001b[38;5;241;43m*\u001b[39;49m\u001b[43mkwargs\u001b[49m\u001b[43m)\u001b[49m\u001b[38;5;241m.\u001b[39mjson())\n", - "File \u001b[0;32m~/miniconda3/envs/py311/lib/python3.11/site-packages/ollama/_client.py:124\u001b[0m, in \u001b[0;36mClient._request_raw\u001b[0;34m(self, *args, **kwargs)\u001b[0m\n\u001b[1;32m 123\u001b[0m \u001b[38;5;28;01mexcept\u001b[39;00m httpx\u001b[38;5;241m.\u001b[39mConnectError:\n\u001b[0;32m--> 124\u001b[0m \u001b[38;5;28;01mraise\u001b[39;00m \u001b[38;5;167;01mConnectionError\u001b[39;00m(CONNECTION_ERROR_MESSAGE) \u001b[38;5;28;01mfrom\u001b[39;00m\u001b[38;5;250m \u001b[39m\u001b[38;5;28;01mNone\u001b[39;00m\n", - "\u001b[0;31mConnectionError\u001b[0m: Failed to connect to Ollama. Please check that Ollama is downloaded, running and accessible. https://ollama.com/download", - "\nThe above exception was the direct cause of the following exception:\n", - "\u001b[0;31mValueError\u001b[0m Traceback (most recent call last)", - "Cell \u001b[0;32mIn[30], line 2\u001b[0m\n\u001b[1;32m 1\u001b[0m \u001b[38;5;66;03m# Using nomic-ai/nomic-embed-text-v1.5 model\u001b[39;00m\n\u001b[0;32m----> 2\u001b[0m emb_model \u001b[38;5;241m=\u001b[39m \u001b[43mEmbeddingWithOllama\u001b[49m\u001b[43m(\u001b[49m\u001b[43mmodel_name\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[38;5;124;43mnomic-embed-text\u001b[39;49m\u001b[38;5;124;43m'\u001b[39;49m\u001b[43m)\u001b[49m\n", - "File \u001b[0;32m~/FORK-AIAgents4Pharma/AIAgents4Pharma/notebook/../aiagents4pharma/talk2knowledgegraphs/utils/embeddings/ollama.py:24\u001b[0m, in \u001b[0;36mEmbeddingWithOllama.__init__\u001b[0;34m(self, model_name)\u001b[0m\n\u001b[1;32m 17\u001b[0m \u001b[38;5;250m\u001b[39m\u001b[38;5;124;03m\"\"\"\u001b[39;00m\n\u001b[1;32m 18\u001b[0m \u001b[38;5;124;03mInitialize the EmbeddingWithOllama class.\u001b[39;00m\n\u001b[1;32m 19\u001b[0m \n\u001b[1;32m 20\u001b[0m \u001b[38;5;124;03mArgs:\u001b[39;00m\n\u001b[1;32m 21\u001b[0m \u001b[38;5;124;03m model_name: The name of the Ollama model to be used.\u001b[39;00m\n\u001b[1;32m 22\u001b[0m \u001b[38;5;124;03m\"\"\"\u001b[39;00m\n\u001b[1;32m 23\u001b[0m \u001b[38;5;66;03m# Setup the Ollama server\u001b[39;00m\n\u001b[0;32m---> 24\u001b[0m \u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43m__setup\u001b[49m\u001b[43m(\u001b[49m\u001b[43mmodel_name\u001b[49m\u001b[43m)\u001b[49m\n\u001b[1;32m 26\u001b[0m \u001b[38;5;66;03m# Set parameters\u001b[39;00m\n\u001b[1;32m 27\u001b[0m \u001b[38;5;28mself\u001b[39m\u001b[38;5;241m.\u001b[39mmodel_name \u001b[38;5;241m=\u001b[39m model_name\n", - "File \u001b[0;32m~/FORK-AIAgents4Pharma/AIAgents4Pharma/notebook/../aiagents4pharma/talk2knowledgegraphs/utils/embeddings/ollama.py:50\u001b[0m, in \u001b[0;36mEmbeddingWithOllama.__setup\u001b[0;34m(self, model_name)\u001b[0m\n\u001b[1;32m 46\u001b[0m \u001b[38;5;28;01mwith\u001b[39;00m subprocess\u001b[38;5;241m.\u001b[39mPopen(\n\u001b[1;32m 47\u001b[0m \u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mollama serve\u001b[39m\u001b[38;5;124m\"\u001b[39m, shell\u001b[38;5;241m=\u001b[39m\u001b[38;5;28;01mTrue\u001b[39;00m, stdout\u001b[38;5;241m=\u001b[39msubprocess\u001b[38;5;241m.\u001b[39mPIPE, stderr\u001b[38;5;241m=\u001b[39msubprocess\u001b[38;5;241m.\u001b[39mPIPE\n\u001b[1;32m 48\u001b[0m ):\n\u001b[1;32m 49\u001b[0m time\u001b[38;5;241m.\u001b[39msleep(\u001b[38;5;241m10\u001b[39m)\n\u001b[0;32m---> 50\u001b[0m \u001b[38;5;28;01mraise\u001b[39;00m \u001b[38;5;167;01mValueError\u001b[39;00m(\u001b[38;5;124mf\u001b[39m\u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mError: \u001b[39m\u001b[38;5;132;01m{\u001b[39;00me\u001b[38;5;132;01m}\u001b[39;00m\u001b[38;5;124m and restarted Ollama server.\u001b[39m\u001b[38;5;124m\"\u001b[39m) \u001b[38;5;28;01mfrom\u001b[39;00m\u001b[38;5;250m \u001b[39m\u001b[38;5;21;01me\u001b[39;00m\n", - "\u001b[0;31mValueError\u001b[0m: Error: Failed to connect to Ollama. Please check that Ollama is downloaded, running and accessible. https://ollama.com/download and restarted Ollama server." - ] - } - ], - "source": [ - "# Using nomic-ai/nomic-embed-text-v1.5 model\n", - "emb_model = EmbeddingWithOllama(model_name='nomic-embed-text')" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Node Embedding" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "We will perform node embedding for the IBD-related nodes using the Ollama model by using mini-batches of 100 nodes at a time." - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Since the records of nodes has large amount of data, we will split them into mini-batches\n", - "mini_batch_size = 100\n", - "node_embeddings = []\n", - "for i in tqdm(range(0, primekg_ibd_nodes_df.shape[0], mini_batch_size)):\n", - " outputs = emb_model.embed_documents(primekg_ibd_nodes_df.enriched_node.values.tolist()[i:i+mini_batch_size])\n", - " node_embeddings.extend(outputs)\n", - "# node_embeddings" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Check the shape of the node embeddings\n", - "len(node_embeddings), len(node_embeddings[0])" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Add them as features to the dataframe\n", - "primekg_ibd_nodes_df['x'] = node_embeddings\n", - "\n", - "# Drop and rename several columns\n", - "primekg_ibd_nodes_df.drop(columns=['node_source', 'node_id'], inplace=True)\n", - "primekg_ibd_nodes_df.rename(columns={'node_index': 'node_id'}, inplace=True)\n", - "\n", - "# Check dataframe of nodes\n", - "primekg_ibd_nodes_df.head()" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Duplicate a node_name as index and use it as index\n", - "primekg_ibd_nodes_df['node'] = primekg_ibd_nodes_df['node_id']\n", - "primekg_ibd_nodes_df.set_index('node', inplace=True)\n", - "primekg_ibd_nodes_df.head()" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Save the embedded nodes dataframes to parquet file\n", - "primekg_ibd_nodes_df.to_parquet(os.path.join(local_dir, 'primekg_ibd_nodes_embedded.parquet'), compression='gzip', index=False)" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "#### Edge Embedding" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Likewise, we also conduct node embedding for the IBD-related edges using the Ollama model by using mini-batches of 100 edges at a time." - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Since the records of edges has large amount of data, we will split them into mini-batches\n", - "mini_batch_size = 100\n", - "edge_embeddings = []\n", - "for i in tqdm(range(0, primekg_ibd_edges_df.shape[0], mini_batch_size)):\n", - " outputs = emb_model.embed_documents(primekg_ibd_edges_df.enriched_edge.values.tolist()[i:i+mini_batch_size])\n", - " edge_embeddings.extend(outputs)\n", - "# edge_embeddings" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Check the shape of the edge embeddings\n", - "len(edge_embeddings), len(edge_embeddings[0])" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Add them as features to the dataframe\n", - "primekg_ibd_edges_df['edge_attr'] = edge_embeddings\n", - "\n", - "# Drop and rename several columns\n", - "primekg_ibd_edges_df.drop(columns=['head_source', 'head_id', 'head_type', 'tail_source', 'tail_id', 'tail_type', 'display_relation', 'relation'], inplace=True)\n", - "primekg_ibd_edges_df.rename(columns={'head_index': 'head_id', 'tail_index': 'tail_id'}, inplace=True)\n", - "\n", - "# Check dataframe of edges\n", - "primekg_ibd_edges_df.head()" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Save the embedded nodes dataframes to parquet file\n", - "primekg_ibd_edges_df.to_parquet(os.path.join(local_dir, 'primekg_ibd_edges_embedded.parquet'), compression='gzip', index=False)" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "### Knowledge Graph Construction" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "For this section, we would like to convert our dataframes to networkx `DiGraph` object." - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Modify the node dataframe\n", - "primekg_ibd_nodes_df[\"node\"] = primekg_ibd_nodes_df.apply(lambda x: f\"{x.node_name}_({x.node_id})\", axis=1)\n", - "primekg_ibd_nodes_df[\"node_id\"] = primekg_ibd_nodes_df.apply(lambda x: f\"{x.node_name}_({x.node_id})\", axis=1)\n", - "primekg_ibd_nodes_df.set_index('node', inplace=True)\n", - "primekg_ibd_nodes_df.head()" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Modify the edge dataframe\n", - "primekg_ibd_edges_df[\"head_id\"] = primekg_ibd_edges_df.apply(lambda x: f\"{x.head_name}_({x.head_id})\", axis=1)\n", - "primekg_ibd_edges_df[\"tail_id\"] = primekg_ibd_edges_df.apply(lambda x: f\"{x.tail_name}_({x.tail_id})\", axis=1)\n", - "primekg_ibd_edges_df.reset_index(drop=True, inplace=True)\n", - "primekg_ibd_edges_df.head()" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# # Convert dataframes to knowledge graph as networkx object\n", - "kg = nx.DiGraph()\n", - "for i, row in primekg_ibd_nodes_df.iterrows():\n", - " kg.add_node(row['node_id'], **row.to_dict())\n", - "for i, row in primekg_ibd_edges_df.iterrows():\n", - " kg.add_edge(row['head_id'], row['tail_id'], key=i, **row.to_dict())\n" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Save graph object\n", - "local_dir = '../../../aiagents4pharma/talk2knowledgegraphs/tests/files/'\n", - "with open(os.path.join(local_dir, 'primekg_ibd_nx_graph.pkl'), 'wb') as f:\n", - " pickle.dump(kg, f)\n", - "\n", - "# # Load graph object\n", - "# with open(os.path.join(local_dir, 'primekg_ibd_nx_graph.pkl'), 'rb') as f:\n", - "# kg = pickle.load(f)\n" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "print (\"#Nodes\", kg.number_of_nodes())\n", - "print (\"#Edges\", kg.number_of_edges())" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "In addition, we can convert the networkx graph to PyG `Data` object for further processing (e.g., subgraph extraction)." - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Convert networkx graph to PyG data object\n", - "pyg_graph = from_networkx(kg)\n", - "\n", - "# Save graph object\n", - "with open(os.path.join(local_dir, 'primekg_ibd_pyg_graph.pkl'), 'wb') as f:\n", - " pickle.dump(pyg_graph, f)\n", - "\n", - "# Load graph object\n", - "# with open(os.path.join(local_dir, 'primekg_ibd_pyg_graph.pkl'), 'rb') as f:\n", - "# pyg_graph = pickle.load(f)" - ] - }, - { - "cell_type": "markdown", - "metadata": {}, - "source": [ - "Lastly, we are going to prepare a textualized graph of nodes and edges for RAG application, for instance.\n" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Prepare nodes\n", - "nodes_df = pd.DataFrame({\n", - " 'node_id': list(pyg_graph.node_id),\n", - " 'node_attr': list(pyg_graph.enriched_node),\n", - "})\n", - "nodes_df" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "# Prepare edges\n", - "edges_df = pd.DataFrame({\n", - " 'head_id': list(pyg_graph.head_id),\n", - " 'edge_type': list(pyg_graph.edge_type),\n", - " 'tail_id': list(pyg_graph.tail_id),\n", - "})\n", - "edges_df" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [ - "with open(os.path.join(local_dir, 'primekg_ibd_text_graph.pkl'), \"wb\") as f:\n", - " pickle.dump({\"nodes\": nodes_df, \"edges\": edges_df}, f)" - ] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [] - }, - { - "cell_type": "code", - "execution_count": null, - "metadata": {}, - "outputs": [], - "source": [] - } - ], - "metadata": { - "kernelspec": { - "display_name": "Python (myenv)", - "language": "python", - "name": "myenv" - }, - "language_info": { - "codemirror_mode": { - "name": "ipython", - "version": 3 - }, - "file_extension": ".py", - "mimetype": "text/x-python", - "name": "python", - "nbconvert_exporter": "python", - "pygments_lexer": "ipython3", - "version": "3.11.11" - } - }, - "nbformat": 4, - "nbformat_minor": 4 -}