RePlaq Team
Sander W. van der Laan, Jessica van Setten, Michal Mokry, Gerard Pasterkamp.
Project ID [RePlaq]
RePlaq: "Replicating the expression quantitative trait loci of carotid Plaques in the Athero-Express Biobank Study" aims to replicate the findings of Folkersen et al. 2010.
We will replicate Folkersen et al. by associating 168 known cardiovascular genetic loci to carotid plaque gene expression.
We have bulk RNAseq (n ± 1,193 samples) and overlapping genetic data for 1,989 individuals with extensive clinical data.
For the eQTL analyses we will use TensorQTL using age, sex (where applicable), genetic principal components, and PEER-factors to account for confounding.
We will perform regression analyses adjusted for age, sex (where applicable) and principal components.
- model 1:
phenotype ~ age + sex + PCs + PEER-factors
Aim 1: Replicate the findings of Folkersen et al. 2010 in the Athero-Express Biobank Study.
Aim 2a: Execute cis- and trans-eQTL analyses using all data to expand the number of eQTLs identified in carotid plaques.
Aim 2b: Execute these eQTL analyses stratified by sex and perform interaction analyses to enrich the interpretability of the eQTLs.
Aim 3: Perform a meta-analysis of the eQTL results with the publically available Folkersen et al. 2010 results.
You can load this project in RStudio by opening the file called 'RePlaq.Rproj'.
| File | Description | Usage |
|---|---|---|
| README.md | Description of project | Human editable |
| RePlaq.Rproj | Project file | Loads project |
| LICENSE | User permissions | Read only |
| .worcs | WORCS metadata YAML | Read only |
| renv.lock | Reproducible R environment | Read only |
| images | image directory for project | Human editable |
| BASELINE | Baseline characteristics directory | Human editable |
| OUTPUT | Output directory | Human editable |
| PLOTS | Some results | Human editable |
| scripts | Scripts directory | Human editable |
| packages.bib | BibTex references for packages used | Human editable |
| references.bib | BibTex references | Human editable |
| 1_AEDB.CEA.baseline.Rmd | Preparing data, baseline table | Human editable |
This notebook is used to create a RDS-formatted datasets with the selection of samples.
In the spirit of Open Science we will preregister this work upon funding through OSF. However, in the spirit of transparency this GitHub is already available for the reviewer.
This project uses the Workflow for Open Reproducible Code in Science (WORCS) to ensure transparency and reproducibility according to the principles of FAIR. The workflow is designed to meet the principles of Open Science throughout a research project.
To learn how WORCS helps researchers meet the TOP-guidelines and FAIR principles, read the preprint at https://osf.io/zcvbs/.
This repository works with renv. This is a package that creates a reproducible environment for your project. It is a good practice to use renv to ensure that your project is reproducible. However, it is not mandatory and it is up to the user to decide whether to use it or not.
- To get started with
worcs, see the setup vignette - For detailed information about the steps of the WORCS workflow, see the workflow vignette
Please refer to the vignette on reproducing a WORCS project for step by step advice.
Dr. Sander W. van der Laan is funded through EU H2020 TO_AITION (grant number: 848146), EU HORIZON NextGen (grant number: 101136962), EU HORIZON MIRACLE (grant number: 101115381), and Health~Holland PPP Allowance ‘Getting the Perfect Image’.
We are thankful for the support of the Leducq Fondation ‘PlaqOmics’ and ‘AtheroGen’, and the Chan Zuckerberg Initiative ‘MetaPlaq’. The research for this contribution was made possible by the AI for Health working group of the EWUU alliance. The collaborative project ‘Getting the Perfect Image’ was co-financed through use of PPP Allowance awarded by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships.
Plaque samples are derived from endarterectomies as part of the Athero-Express Biobank Study which is an ongoing study in the UMC Utrecht. We would like to thank all the (former) employees involved in the Athero-Express Biobank Study of the Departments of Surgery of the St. Antonius Hospital Nieuwegein and University Medical Center Utrecht for their continuing work. Lastly, we would like to thank all participants of the Athero-Express Biobank Study; without you these kinds of studies would not be possible.
The framework was based on the WORCS package.
Dr. Sander W. van der Laan has received Roche funding for unrelated work.
_Version:_ v1.0.0</br>
_Last update:_ 2025-03-05</br>
_Written by:_ Sander W. van der Laan (s.w.vanderlaan [at] gmail [dot] com).
**MoSCoW To-Do List**
The things we Must, Should, Could, and Would have given the time we have.
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**Changes log**
* v1.0.0 Initial version. Based on AE_TEMPLATE (v1.4.6).