<div dir="ltr">Hi Will<div><br></div><div>I now understand the issue.</div><div><br></div><div>And no... I do not think you should add a no_consequence type, but I do think that it should not print out anything for that sample, even with the -most_severe flag on. </div>
<div><br></div><div>Since it is a non-variant it should not output anything. without the --filter_common out and the --most_severe flag on , the output should be 7 lines of annotation one for each sample that has that variation genotyped.</div>
<div><br></div><div>Does this make sense? I rarely use the most-severe flag anyway, so it does not affect me much, but it might induce people in error that are not aware of this default behavior. In the case, as an example, this is a non-coding exon variant and the output for that single sample might induce errors of analysis for many people.</div>
<div><br></div><div>Best regards</div><div><br>Duarte</div><div><br></div></div><div class="gmail_extra"><br clear="all"><div><font style="background-color:rgb(255,255,255)" color="#999999">=========================<br> Duarte Miguel Paulo Molha <br>
</font><div><font style="background-color:rgb(255,255,255)" color="#999999"> <a href="http://about.me/duarte" target="_blank">http://about.me/duarte</a> <br>=========================</font></div></div>
<br><br><div class="gmail_quote">On Tue, Aug 27, 2013 at 3:28 PM, Will McLaren <span dir="ltr"><<a href="mailto:wm2@ebi.ac.uk" target="_blank">wm2@ebi.ac.uk</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
<div dir="ltr">Ah, sorry, I wasn't testing with --filter_common.<div><br></div><div>However, if I add --filter_common, I don't see any lines in the output, and the VEP reports all 9 variants/individuals are being filtered out. rs4372192 overlaps and has a frequency of 0.08.</div>
<div><br></div><div>Perhaps your API and/or script is out of date? Though I still don't see the problem even if I test it with v71...</div><span class="HOEnZb"><font color="#888888"><div><br></div><div>Will</div></font></span></div>
<div class="HOEnZb"><div class="h5"><div class="gmail_extra"><br><br><div class="gmail_quote">
On 27 August 2013 15:03, Duarte Molha <span dir="ltr"><<a href="mailto:duartemolha@gmail.com" target="_blank">duartemolha@gmail.com</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
<div dir="ltr">My script does not output any information for the remaining 8 samples. If I understand correctly from your email, your script is outputting the other samples.<div><br></div><div>What might be causing the discrepancy?</div>
<div><br></div><div>Best regards</div><div><br></div><div>Duarte</div><div><br></div></div><div class="gmail_extra"><br clear="all"><div><font color="#999999">=========================<br>
Duarte Miguel Paulo Molha <br></font><div><font color="#999999"> <a href="http://about.me/duarte" target="_blank">http://about.me/duarte</a> <br>=========================</font></div>
</div><div><div>
<br><br><div class="gmail_quote">On Tue, Aug 27, 2013 at 2:50 PM, Duarte Molha <span dir="ltr"><<a href="mailto:Duarte.Molha@ogt.com" target="_blank">Duarte.Molha@ogt.com</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
<div lang="EN-GB" link="blue" vlink="purple"><div><p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1f497d">My apologies Will, but I think you are missing a bit of my problem.<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1f497d"><u></u> <u></u></span></p><p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1f497d">This not a non-variant variation for the remaining individuals/samples . Why are they not being output?<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1f497d"><u></u> <u></u></span></p><p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1f497d">Cheers<u></u><u></u></span></p>
<p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1f497d"><br>Duarte<u></u><u></u></span></p><p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1f497d"><u></u> <u></u></span></p>
<p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1f497d"><u></u> <u></u></span></p><p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Calibri","sans-serif";color:#1f497d"><u></u> <u></u></span></p>
<p class="MsoNormal"><b><span lang="EN-US" style="font-size:10.0pt;font-family:"Tahoma","sans-serif"">From:</span></b><span lang="EN-US" style="font-size:10.0pt;font-family:"Tahoma","sans-serif""> <a href="mailto:dev-bounces@ensembl.org" target="_blank">dev-bounces@ensembl.org</a> [mailto:<a href="mailto:dev-bounces@ensembl.org" target="_blank">dev-bounces@ensembl.org</a>] <b>On Behalf Of </b>Will McLaren<br>
<b>Sent:</b> 27 August 2013 14:45<br><b>To:</b> Ensembl developers list<br><b>Subject:</b> Re: [ensembl-dev] bug in the VEP annotation of VCFs with multiple individuals<u></u><u></u></span></p><div><div><p class="MsoNormal">
<u></u> <u></u></p><div><p class="MsoNormal">Hi Duarte,<u></u><u></u></p><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p class="MsoNormal">Thanks for raising this. There's an interesting quirk here which seems to be what you're looking at. However, I _do_ see lines of output for the other 8 individuals in the file.<u></u><u></u></p>
</div><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p class="MsoNormal">What is it you would expect to see for sample9? Would you expect that line to be excluded from the output?<u></u><u></u></p></div><div><p class="MsoNormal">
<u></u> <u></u></p></div><div><p class="MsoNormal">The reason it is shown is because you are using most_severe, which forces the VEP to give the most severe consequence per variant (which I would generally advise against using!) - when using --individual each individual/variant combination is considered as an independent variant.<u></u><u></u></p>
</div><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p class="MsoNormal">The reason it is intergenic_variant is because that is the "default" consequence - since the locus is non-variant for sample9, it does not go through the consequence prediction, but because you are forcing it to be printed out with most_severe, the VEP has to default to using intergenic_variant.<u></u><u></u></p>
</div><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p class="MsoNormal">I could see two solutions - either excluding the line (since it is non-variant), or having some sort of "no consequence" type - which I am loathe to do as this doesn't fit in to our SO schema.<u></u><u></u></p>
</div><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p class="MsoNormal">Will<u></u><u></u></p></div></div><div><p class="MsoNormal" style="margin-bottom:12.0pt"><u></u> <u></u></p><div><p class="MsoNormal">On 27 August 2013 12:16, Duarte Molha <<a href="mailto:duartemolha@gmail.com" target="_blank">duartemolha@gmail.com</a>> wrote:<u></u><u></u></p>
<div><p class="MsoNormal">Dear Developers<u></u><u></u></p><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p class="MsoNormal">I believe there is another bug in the VEP when dealing with input VCFs with multiple individuals...<u></u><u></u></p>
</div><div><p class="MsoNormal">Please take a look at this VCF input and the corresponding output:<u></u><u></u></p></div><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p class="MsoNormal">INPUT VCF line:<u></u><u></u></p>
</div><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p>#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT sample1 sample2 sample3 sample4 sample5 sample6 sample7 sample8 sample9<u></u><u></u></p>
<p>1 876499 . A G 2900.87 PASS AC=15;AF=0.938;AN=16;BaseQRankSum=1.636;DP=92;Dels=0.00;FS=0.000;HRun=6;HaplotypeScore=0.4159;MQ=59.36;MQ0=0;MQRankSum=1.274;QD=31.53;ReadPosRankSum=-0.482;SB=-1653.87;set=variant2 GT:AD:DP:GQ:PL 1/1:0,9:9:24.07:303,24,0 1/1:0,10:10:27.09:365,27,0 0/1:5,4:9:99:104,0,166 1/1:0,7:7:18.04:220,18,0 1/1:0,16:16:39.13:534,39,0 1/1:0,12:12:30.10:407,30,0 1/1:0,14:14:39.13:535,39,0 1/1:0,15:15:36.12:483,36,0 ./.<u></u><u></u></p>
</div><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p class="MsoNormal">OUTPUT annotation file:<u></u><u></u></p></div><div><p>#Uploaded_variation Location Existing_variation Allele ZYG Gene Feature Feature_type Consequence GMAF IND<u></u><u></u></p>
<p>1_876499_A 1:876499 rs4372192 - HOM - - - intergenic_variant A:0.0824 sample9<u></u><u></u></p></div><div><div><p class="MsoNormal"><u></u> <u></u></p></div><div>
<p class="MsoNormal">As you can see, the annotation output only contains 1 line and it is for the individual that has no genotype call (./.)<u></u><u></u></p></div><div><p class="MsoNormal"><u></u> <u></u></p></div><div>
<p class="MsoNormal">
Also, the variation name does not contain the ref/alt_allele information on the name as all other variations. I would expect if to be called 1_876499_A/G<u></u><u></u></p></div><div><p class="MsoNormal"><u></u> <u></u></p>
</div><div><p class="MsoNormal">For reference here are the config options I used:<u></u><u></u></p></div><div><p class="MsoNormal"><u></u> <u></u></p></div><div><p>host [internalserver]user [user]<u></u><u></u></p>
<p>password [password]<u></u><u></u></p><p>db_version 72 <u></u><u></u></p><p>port 3306 <u></u><u></u></p>
<p>species homo_sapiens<u></u><u></u></p><p> <u></u><u></u></p><p>####### runtime options #############<u></u><u></u></p><p>buffer_size 40000<u></u><u></u></p>
<p>most_severe 1<u></u><u></u></p><p>check_existing 1<u></u><u></u></p><p>check_alleles 1<u></u><u></u></p><p>individual all<u></u><u></u></p>
<p>fork 6<u></u><u></u></p><p> verbose 1<u></u><u></u></p><p> gmaf 1<u></u><u></u></p>
<p>filter_common 1<u></u><u></u></p><p>fields Uploaded_variation,Location,Existing_variation,Allele,ZYG,Gene,Feature,Feature_type,Consequence,GMAF,IND<u></u><u></u></p><p><u></u> <u></u></p><p>####### cache stuff ############# <u></u><u></u></p>
<p>cache 1<u></u><u></u></p><p>dir_plugins /NGS_Test/vep_72_testing/Plugins/<u></u><u></u></p><p>dir_cache /ReferenceData/vep_cache<u></u><u></u></p>
<p># cache_region_size 1MB<u></u><u></u></p><p>#offline 1<u></u><u></u></p><p># skip_db_check 1<u></u><u></u></p><p><u></u> <u></u></p></div>
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