<div dir="ltr">Hi Jessica,<div><div class="gmail_extra"><br><div class="gmail_quote">On 9 November 2015 at 00:20, Jessica Chong <span dir="ltr"><<a href="mailto:jxchong@uw.edu" target="_blank">jxchong@uw.edu</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left-width:1px;border-left-color:rgb(204,204,204);border-left-style:solid;padding-left:1ex">I am trying to use the --gene_phenotype option in VEP v82 but I am having problems.<br>
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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">http://uswest.ensembl.org/info/docs/tools/vep/vep_formats.html#output</a></blockquote><div><br></div><div>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><div><br></div><div>Example for CFTR: <a href="http://www.ensembl.org/Homo_sapiens/Gene/Phenotype?g=ENSG00000001626">http://www.ensembl.org/Homo_sapiens/Gene/Phenotype?g=ENSG00000001626</a></div><div> </div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left-width:1px;border-left-color:rgb(204,204,204);border-left-style:solid;padding-left:1ex"><br>
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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></blockquote><div><br></div><div>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">http://www.ensembl.org/info/docs/tools/vep/vep_formats.html#output</a> shows the output fields and their descriptions.</div><div> </div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left-width:1px;border-left-color:rgb(204,204,204);border-left-style:solid;padding-left:1ex">
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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></blockquote><div><br></div><div>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><div><br></div><div>I will look into why this information is missing.</div><div><br></div><div>Regards</div><div><br></div><div>Will McLaren</div><div>Ensembl Variation</div><div> </div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left-width:1px;border-left-color:rgb(204,204,204);border-left-style:solid;padding-left:1ex">
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Here is what I ran:<br>
perl variant_effect_predictor/<a href="http://variant_effect_predictor.pl" rel="noreferrer" target="_blank">variant_effect_predictor.pl</a> \<br>
-i CFTR.VT.vcf \<br>
-o CFTR.VT.VEP.vcf \<br>
--vcf --offline --cache \<br>
--dir_cache variant_effect_predictor/cache/ \<br>
--species homo_sapiens --assembly GRCh37 \<br>
--fasta Homo_sapiens_assembly19.fasta \<br>
--fork 8 --force_overwrite \<br>
--compress 'gunzip -c' \<br>
--sift b --polyphen b --symbol --numbers --biotype \<br>
--total_length --canonical --ccds --hgvs --shift_hgvs 1 --gene_phenotype \<br>
--fields Consequence,Codons,Amino_acids,Gene,SYMBOL,Feature,EXON,PolyPhen,SIFT,Protein_position,BIOTYPE,CANONICAL,CCDS,HGVSc,HGVSp,PHENO<br>
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The resulting vcf contains these lines:<br>
##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>
##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>
#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT sample1A3 sample1A4 sample1A5 sample1A6 sample1A7 sample1A8 sample1A3 sample1A4 sample1A5 sample1A6 sample1A7 sample1A8<br>
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>
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Thanks!<br>
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