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Hi Will,
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<div class="">On Nov 9, 2015, at 1:44 AM, Will McLaren <<a href="mailto:wm2@ebi.ac.uk" class="">wm2@ebi.ac.uk</a>> wrote:</div>
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<div dir="ltr" class="">Hi Jessica,
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<div class="gmail_quote">On 9 November 2015 at 00:20, Jessica Chong <span dir="ltr" class="">
<<a href="mailto:jxchong@uw.edu" target="_blank" class="">jxchong@uw.edu</a>></span> wrote:<br class="">
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I am trying to use the --gene_phenotype option in VEP v82 but I am having problems.<br class="">
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1) if a variant is in a gene that is associated with a particular phenotype (e.g. CFTR and cystic fibrosis), where does this information get stored in the resulting annotated vcf? I don’t see a corresponding field name listed as a possible extras column output
on this page <a href="http://uswest.ensembl.org/info/docs/tools/vep/vep_formats.html#output" rel="noreferrer" target="_blank" class="">
http://uswest.ensembl.org/info/docs/tools/vep/vep_formats.html#output</a></blockquote>
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<div class="">The phenotype name does not get stored in the output. Firstly, many phenotype names are long and contain odd characters that can break file format encoding. Secondly, many genes and/or variants have several phenotypes associated with them, so
to list all of them (and multiple times in the case where you are reporting e.g. the same gene multiple times) would cause the output file size to increase hugely.</div>
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<div class="">Example for CFTR: <a href="http://www.ensembl.org/Homo_sapiens/Gene/Phenotype?g=ENSG00000001626" class="">http://www.ensembl.org/Homo_sapiens/Gene/Phenotype?g=ENSG00000001626</a></div>
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<div>Ok, I see. Thanks.</div>
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2) if a variant itself is associated with a particular “phenotype, disease, or trait” then my understanding from the VEP output documentation is that I should expect this information to show up under the PHENO field?<br class="">
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<div class="">I don't think this is stated anywhere in the documentation. <a href="http://www.ensembl.org/info/docs/tools/vep/vep_formats.html#output" class="">http://www.ensembl.org/info/docs/tools/vep/vep_formats.html#output</a> shows the output fields and
their descriptions.</div>
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<div>Ahhh, ok. Because GENE_PHENO isn’t listed in the VEP documentation as a possible output field, the closest I could find was “PHENO,” so I was just guessing.</div>
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I tried annotating a tiny vcf that just includes a variant in CFTR (and the variant is dF508, so it is definitely pathogenic and CFTR should certainly be associated with a phenotype as well on the gene level) but PHENO is always blank (and I don’t see any field
mentioning cystic fibrosis as a phenotype/disease name).<br class="">
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<div class="">Apologies, there seems to be an issue with the v82 caches in that they are missing the necessary information to populate the fields for --gene_phenotype. However, the field you want is GENE_PHENO, which should show a binary flag indicating whether
the gene is associated with a phenotype.</div>
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<div class="">I will look into why this information is missing.</div>
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<div>Thanks!</div>
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<div class="">Regards</div>
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<div class="">Will McLaren</div>
<div class="">Ensembl Variation</div>
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Here is what I ran:<br class="">
perl variant_effect_predictor/<a href="http://variant_effect_predictor.pl/" rel="noreferrer" target="_blank" class="">variant_effect_predictor.pl</a> \<br class="">
-i CFTR.VT.vcf \<br class="">
-o CFTR.VT.VEP.vcf \<br class="">
--vcf --offline --cache \<br class="">
--dir_cache variant_effect_predictor/cache/ \<br class="">
--species homo_sapiens --assembly GRCh37 \<br class="">
--fasta Homo_sapiens_assembly19.fasta \<br class="">
--fork 8 --force_overwrite \<br class="">
--compress 'gunzip -c' \<br class="">
--sift b --polyphen b --symbol --numbers --biotype \<br class="">
--total_length --canonical --ccds --hgvs --shift_hgvs 1 --gene_phenotype \<br class="">
--fields Consequence,Codons,Amino_acids,Gene,SYMBOL,Feature,EXON,PolyPhen,SIFT,Protein_position,BIOTYPE,CANONICAL,CCDS,HGVSc,HGVSp,PHENO<br class="">
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The resulting vcf contains these lines:<br class="">
##VEP=v82 cache=/ensembl-tools/82/Linux/RHEL6/x86_64/variant_effect_predictor/cache//homo_sapiens/82_GRCh37 db=. polyphen=2.2.2 sift=sift5.2.2 COSMIC=71 ESP=20141103 gencode=GENCODE 19 HGMD-PUBLIC=20152 genebuild=2011-04 regbuild=13 assembly=GRCh37.p13 dbSNP=144
ClinVar=201507<br class="">
##INFO=<ID=CSQ,Number=.,Type=String,Description="Consequence annotations from Ensembl VEP. Format: Consequence|Codons|Amino_acids|Gene|SYMBOL|Feature|EXON|PolyPhen|SIFT|Protein_position|BIOTYPE|CANONICAL|CCDS|HGVSc|HGVSp|PHENO”><br class="">
#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT sample1A3 sample1A4 sample1A5 sample1A6 sample1A7 sample1A8 sample1A3 sample1A4 sample1A5 sample1A6 sample1A7 sample1A8<br class="">
7 117199644 rs199826652 ATCT A 3996.41 PASS AC=4;AF=0.023;AN=24;BaseQRankSum=-0.941;ClippingRankSum=-0.033;DB;DP=7203;FS=2.556;InbreedingCoeff=-0.0257;MLEAC=5;MLEAF=0.023;MQ0=0;MQ=60.36;MQRankSum=0.129;QD=21.37;ReadPosRankSum=0.673;SOR=0.921;VQSLOD=1.51;culprit=SOR;CSQ=downstream_gene_variant|||ENSG00000232661|AC000111.3|ENST00000441019|||||antisense|YES||||,inframe_deletion|aTCTtt/att|IF/I|ENSG00000001626|CFTR|ENST00000426809|10/26|||477-478/1438|protein_coding|||ENST00000426809.1:c.1431_1433delCTT|ENSP00000389119.1:p.Phe478del|,inframe_deletion|aTCTtt/att|IF/I|ENSG00000001626|CFTR|ENST00000454343|10/26|||446-447/1419|protein_coding|||ENST00000454343.1:c.1338_1340delCTT|ENSP00000403677.1:p.Phe447del|,inframe_deletion|aTCTtt/att|IF/I|ENSG00000001626|CFTR|ENST00000003084|11/27|||507-508/1480|protein_coding|YES|CCDS5773.1|ENST00000003084.6:c.1521_1523delCTT|ENSP00000003084.6:p.Phe508del|,upstream_gene_variant|||ENSG00000001626|CFTR|ENST00000472848|||||processed_transcript|||||
GT:AD:DP:GQ:PL 0/0:4,0:4:9:0,9,135 0/0:10,0:10:24:0,24,360 0/0:3,0:3:5:0,5,86 0/1:10,12:22:99:441,0,474 0/1:9,18:27:99:729,0,424 0/0:23,0:23:63:0,63,945 0/0:22,0:22:66:0,66,714 0/0:33,0:33:84:0,84,1096 0/0:22,0:22:62:0,62,736
0/1:17,14:31:99:537,0,881 0/1:13,16:29:99:620,0,632 0/0:24,0:24:60:0,60,791<br class="">
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Thanks!<br class="">
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