Disable filter-vcf by default; update fasta path; better notes

Author: ckandoth

README.md

@@ -1,4 +1,4 @@
-vcf<img src="http://i.giphy.com/R6X7GehJWQYms.gif" width="30">maf
+vcf<img src="https://i.giphy.com/R6X7GehJWQYms.gif" width="28">maf
 =======
 
 To convert a [VCF](http://samtools.github.io/hts-specs/) into a [MAF](https://docs.gdc.cancer.gov/Data/File_Formats/MAF_Format), each variant must be mapped to only one of all possible gene transcripts/isoforms that it might affect. But even within a single isoform, a `Missense_Mutation` close enough to a `Splice_Site`, can be labeled as either in MAF format, but not as both. **This selection of a single effect per variant, is often subjective. And that's what this project attempts to standardize.** The `vcf2maf` and `maf2maf` scripts leave most of that responsibility to [Ensembl's VEP](http://useast.ensembl.org/info/docs/tools/vep/index.html), but allows you to override their "canonical" isoforms, or use a custom ExAC VCF for annotation. Though the most useful feature is the **extensive support in parsing a wide range of crappy MAF-like or VCF-like formats** we've seen out in the wild.
@@ -15,23 +15,23 @@ Find the [latest stable release](https://github.com/mskcc/vcf2maf/releases), dow
     perl vcf2maf.pl --man
     perl maf2maf.pl --man
 
-If you don't have [VEP](http://useast.ensembl.org/info/docs/tools/vep/index.html) installed, then [follow this gist](https://gist.github.com/ckandoth/61c65ba96b011f286220fa4832ad2bc0). Of the many annotators out there, VEP is preferred for its large team of active coders, and its CLIA-compliant [HGVS formats](http://www.hgvs.org/mutnomen/recs.html). After installing VEP, you can test the script like so:
+If you don't have [VEP](http://useast.ensembl.org/info/docs/tools/vep/index.html) installed, then [follow this gist](https://gist.github.com/ckandoth/61c65ba96b011f286220fa4832ad2bc0). Of the many annotators out there, VEP is preferred for its large team of active coders, and its CLIA-compliant [HGVS formats](http://www.hgvs.org/mutnomen/recs.html). After installing VEP, test out `vcf2maf` like this:
 
     perl vcf2maf.pl --input-vcf tests/test.vcf --output-maf tests/test.vep.maf
 
 To fill columns 16 and 17 of the output MAF with tumor/normal sample IDs, and to parse out genotypes and allele counts from matched genotype columns in the VCF, use options `--tumor-id` and `--normal-id`. Skip option `--normal-id` if you didn't have a matched normal:
 
     perl vcf2maf.pl --input-vcf tests/test.vcf --output-maf tests/test.vep.maf --tumor-id WD1309 --normal-id NB1308
 
-VCFs from variant callers like [VarScan](http://varscan.sourceforge.net/somatic-calling.html#somatic-output) use hardcoded sample IDs TUMOR/NORMAL in the genotype columns of the VCF. To have this script correctly parse the correct genotype columns, while still printing the proper IDs in the output MAF:
+VCFs from variant callers like [VarScan](http://varscan.sourceforge.net/somatic-calling.html#somatic-output) use hardcoded sample IDs TUMOR/NORMAL to name genotype columns. To have `vcf2maf` correctly locate the columns to parse genotypes, while still printing proper sample IDs in the output MAF:
 
     perl vcf2maf.pl --input-vcf tests/test_varscan.vcf --output-maf tests/test_varscan.vep.maf --tumor-id WD1309 --normal-id NB1308 --vcf-tumor-id TUMOR --vcf-normal-id NORMAL
 
-If you have the VEP script in a different folder like `/opt/vep`, and its cache in `/srv/vep`, there are options available to use those instead:
+If VEP is installed under `/opt/vep` and the VEP cache is under `/srv/vep`, there are options available to tell `vcf2maf` where to find them:
 
     perl vcf2maf.pl --input-vcf tests/test.vcf --output-maf tests/test.vep.maf --vep-path /opt/vep --vep-data /srv/vep
 
-If you want to skip running VEP and need a minimalist MAF format listing data from the input VCF only, then use the `--inhibit-vep` option. If your input VCF contains VEP annotation, then `vcf2maf` will try to extract it. But be warned that the accuracy of your resulting MAF depends on how VEP was operated upstream. `vcf2maf` operates VEP with very specific parameters to make sure everyone has comparable MAFs.
+If you want to skip running VEP and need a minimalist MAF-like file listing data from the input VCF only, then use the `--inhibit-vep` option. If your input VCF contains VEP annotation, then `vcf2maf` will try to extract it. But be warned that the accuracy of your resulting MAF depends on how VEP was operated upstream. In standard operation, `vcf2maf` runs VEP with very specific parameters to make sure everyone produces comparable MAFs. So, it is strongly recommended to avoid `--inhibit-vep` unless you know what you're doing.
 
 maf2maf
 -------
@@ -53,3 +53,8 @@ License
 -------
 
     Apache-2.0 | Apache License, Version 2.0 | https://www.apache.org/licenses/LICENSE-2.0
+
+Citation
+--------
+
+    Cyriac Kandoth. mskcc/vcf2maf: vcf2maf v1.6.19. (2020). doi:10.5281/zenodo.593251

vcf2maf.pl

@@ -13,8 +13,8 @@
 
 # Set any default paths and constants
 my ( $tumor_id, $normal_id ) = ( "TUMOR", "NORMAL" );
-my ( $vep_path, $vep_data, $vep_forks, $buffer_size, $any_allele, $inhibit_vep, $online ) = ( "$ENV{HOME}/vep", "$ENV{HOME}/.vep", 4, 5000, 0, 0, 0 );
-my ( $ref_fasta, $filter_vcf ) = ( "$ENV{HOME}/.vep/homo_sapiens/95_GRCh37/Homo_sapiens.GRCh37.75.dna.primary_assembly.fa.gz", "$ENV{HOME}/.vep/ExAC_nonTCGA.r0.3.1.sites.vep.vcf.gz" );
+my ( $vep_path, $vep_data, $vep_forks, $buffer_size, $any_allele, $inhibit_vep, $online ) = ( "$ENV{HOME}/miniconda3/bin", "$ENV{HOME}/.vep", 4, 5000, 0, 0, 0 );
+my ( $ref_fasta, $filter_vcf ) = ( "$ENV{HOME}/.vep/homo_sapiens/101_GRCh37/Homo_sapiens.GRCh37.dna.toplevel.fa.gz", "" );
 my ( $species, $ncbi_build, $cache_version, $maf_center, $retain_info, $retain_fmt, $min_hom_vaf, $max_filter_ac ) = ( "homo_sapiens", "GRCh37", "", ".", "", "", 0.7, 10 );
 my $perl_bin = $Config{perlpath};
 
@@ -392,8 +392,7 @@ sub GetBiotypePriority {
 # ::NOTE:: If input had no variants, don't break here, so we can continue to create an empty MAF
 ( !@regions_split or %flanking_bps ) or die "ERROR: You're either using an outdated samtools, or --ref-fasta is not the same genome build as your --input-vcf.";
 
-# Skip filtering if not handling GRCh37, and filter-vcf is pointing to the default GRCh37 ExAC VCF
-if(( $species eq "homo_sapiens" and $ncbi_build eq "GRCh37" and $filter_vcf ) or ( $filter_vcf and $filter_vcf ne "$ENV{HOME}/.vep/ExAC_nonTCGA.r0.3.1.sites.vep.vcf.gz" )) {
+if( $filter_vcf ) {
     ( -s $filter_vcf ) or die "ERROR: Provided --filter-vcf is missing or empty: $filter_vcf\n";
     # Query each variant locus on the filter VCF, using tabix, just like we used samtools earlier
     ( $lines, @regions_split ) = ( "", ());
@@ -436,7 +435,7 @@ sub GetBiotypePriority {
     warn "STATUS: Running VEP and writing to: $output_vcf\n";
     # Make sure we can find the VEP script
     my $vep_script = ( -s "$vep_path/vep" ? "$vep_path/vep" : "$vep_path/variant_effect_predictor.pl" );
-    ( -s $vep_script ) or die "ERROR: Cannot find VEP script in path: $vep_path\n";
+    ( -s $vep_script ) or die "ERROR: Cannot find VEP script under: $vep_path\n";
 
     # Contruct VEP command using some default options and run it
     my $vep_cmd = "$perl_bin $vep_script --species $species --assembly $ncbi_build --no_progress --no_stats --buffer_size $buffer_size --sift b --ccds --uniprot --hgvs --symbol --numbers --domains --gene_phenotype --canonical --protein --biotype --uniprot --tsl --variant_class --shift_hgvs 1 --check_existing --total_length --allele_number --no_escape --xref_refseq --failed 1 --vcf --flag_pick_allele --pick_order canonical,tsl,biotype,rank,ccds,length --dir $vep_data --fasta $ref_fasta --format vcf --input_file $input_vcf --output_file $output_vcf";
@@ -1136,12 +1135,12 @@ =head1 OPTIONS
  --any-allele     When reporting co-located variants, allow mismatched variant alleles too
  --inhibit-vep    Skip running VEP, but extract VEP annotation in VCF if found
  --online         Use useastdb.ensembl.org instead of local cache (supports only GRCh38 VCFs listing <100 events)
- --ref-fasta      Reference FASTA file [~/.vep/homo_sapiens/95_GRCh37/Homo_sapiens.GRCh37.75.dna.primary_assembly.fa.gz]
- --filter-vcf     A VCF for FILTER tag common_variant. Set to 0 to disable [~/.vep/ExAC_nonTCGA.r0.3.1.sites.vep.vcf.gz]
+ --ref-fasta      Reference FASTA file [~/.vep/homo_sapiens/101_GRCh37/Homo_sapiens.GRCh37.dna.toplevel.fa.gz]
+ --filter-vcf     A VCF for FILTER tag common_variant; Disabled by default []
  --max-filter-ac  Use tag common_variant if the filter-vcf reports a subpopulation AC higher than this [10]
  --species        Ensembl-friendly name of species (e.g. mus_musculus for mouse) [homo_sapiens]
  --ncbi-build     NCBI reference assembly of variants MAF (e.g. GRCm38 for mouse) [GRCh37]
- --cache-version  Version of offline cache to use with VEP (e.g. 75, 84, 91) [Default: Installed version]
+ --cache-version  Version of offline cache to use with VEP (e.g. 75, 91, 101) [Default: Installed version]
  --maf-center     Variant calling center to report in MAF [.]
  --retain-info    Comma-delimited names of INFO fields to retain as extra columns in MAF []
  --retain-fmt     Comma-delimited names of FORMAT fields to retain as extra columns in MAF []