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<p>After thinking about this more, I do have more questions about these discrepancies.</p>
<p>What version of PolyPhen is VEP 88 utilizing for GRCh37? I thought I saw somewhere PolyPhen 2.2.2 was used, which should match dbNSFP v3.0.</p>
<p>Additionally, I am running VEP with the PolyPhen-SIFT plugin. What effect would this have on discrepancies?</p>
<p><br>
</p>
<p>Brad<br>
</p>
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<div id="divRplyFwdMsg" dir="ltr"><font style="font-size:11pt" color="#000000" face="Calibri, sans-serif"><b>From:</b> Dev <dev-bounces@ensembl.org> on behalf of Crone, Bradley <bradley-crone@uiowa.edu><br>
<b>Sent:</b> Tuesday, June 13, 2017 8:08:01 AM<br>
<b>To:</b> Ensembl developers list<br>
<b>Subject:</b> Re: [ensembl-dev] PolyPhen2 prediction discrepancies between VEP 88 and dbNSFP v3.0</font>
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<p>Yes, I did inadvertently include those two examples in my list - predictions do not match (P vs. D), but scores do match across all three.</p>
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</p>
<p>Thanks for the information, I'll look for the update to GRCh37 in July.</p>
<p><br>
</p>
<p>Brad<br>
</p>
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<div id="divRplyFwdMsg" dir="ltr"><font style="font-size:11pt" color="#000000" face="Calibri, sans-serif"><b>From:</b> Dev <dev-bounces@ensembl.org> on behalf of Sarah Hunt <seh@ebi.ac.uk><br>
<b>Sent:</b> Tuesday, June 13, 2017 6:21:26 AM<br>
<b>To:</b> Ensembl developers list<br>
<b>Subject:</b> Re: [ensembl-dev] PolyPhen2 prediction discrepancies between VEP 88 and dbNSFP v3.0</font>
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<p>Hi Brad,</p>
<p><br>
</p>
<p>We do find differences between different PolyPhen analyses, dependent on code version and protein databases used. Our GRCh37 database will be updated to the latest PolyPhen version in July, so do expect some changes. There are a number of genes returning
unknown classifications in our GRCh37 databases, which have calls in our GRCh38 databases which have already been updated to the newer version, so we hope the update improves GRCh37 coverage. An example from your list:<br>
</p>
<p><br>
</p>
<p><a class="moz-txt-link-freetext" href="http://grch37.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:103427257-103428257;v=rs754273408;vdb=variation;vf=119985449" id="LPlnk811766" previewremoved="true">http://grch37.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:103427257-103428257;v=rs754273408;vdb=variation;vf=119985449</a><br>
</p>
<p><a class="moz-txt-link-freetext" href="http://www.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:102961701-102962701;v=rs754273408;vdb=variation;vf=119958041" id="LPlnk489034" previewremoved="true">http://www.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:102961701-102962701;v=rs754273408;vdb=variation;vf=119958041</a></p>
<p><br>
</p>
<p>Thanks for the examples, but I find them a little confusing. Don't 2 of them (10-73377145 & 1-103462662) show agreement across all three versions?<br>
</p>
<p><br>
</p>
<p>Best wishes,</p>
<p><br>
</p>
<p>Sarah<br>
</p>
<p><br>
</p>
<div class="moz-cite-prefix">On 12/06/2017 17:05, Crone, Bradley wrote:<br>
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<p>Hello,</p>
<p><br>
</p>
<p>I'm working with PolyPhen2 scores and predictions in VEP 88 and comparing these back to scores reported in dbNSFP v3.0.</p>
<p>I find a large number of discrepancies between HumDiv scores from VEP and dbNSFP. I've looked at a small subset of 10 mismatches.</p>
<p>Directly comparing scores/predictions with PolyPhen2's website, all PolyPhen2 scores match with a dbNSFP score, and not a VEP score:</p>
<p><br>
</p>
<div>CHROM POS REF ALT GENE VEP-FEATURE VEP-IMPACT VEP_CSQ VEP_POLYPHEN_SCORE VEP_POLYPHEN_PRED DBNSFP_POLYPHEN2_HDIV_SCORE DBNSFP_POLYPHEN2_HDIV_PRED pph2_prob pph2_FPR pph2_TPR<br>
2 73679572 C A ALMS1 NM_015120.4 MODERATE missense_variant 0.952 P 0.987,0.972,0.026 D,D,B 0.026 0.188 0.949<br>
1 216011417 A T USH2A NM_206933.2 MODERATE missense_variant 0.155 B 0.933 P 0.933 0.0573 0.804<br>
12 48398104 T C COL2A1 NM_001844.4 HIGH start_lost 0 U 0.219,0.14 B 0.14 0.136 0.923<br>
1 103427757 C G COL11A1 NM_080629.2 MODERATE missense_variant 0 U 0.999 D 0.999 0.00574 0.136<br>
12 48377197 G T COL2A1 NM_001844.4 MODERATE missense_variant 0.784 P 0.001,0.0 B 0 1 1<br>
6 70981396 C A COL9A1 NM_001851.4 MODERATE missense_variant 0.555 P 0.31,0.0 B 0.31 0.112 0.904<br>
10 73377145 G A CDH23 NM_001171930.1 MODERATE missense_variant 1 P 1.0,1.0,0.998 D 1 0.00026 0.00018<br>
1 216496954 T C USH2A NM_206933.2 MODERATE missense_variant 1 P 0.971,0.413 D,B 0.413 0.103 0.893<br>
17 18064707 C A MYO15A NM_016239.3 MODERATE missense_variant 0 U 0.941,0.761,0.165,0.523,0.981,0.953 P,P,B,P,D,P 0.523 0.0959 0.882<br>
1 103462662 C T COL11A1 NM_001190709.1 MODERATE missense_variant 1 P 1.0 D 1 0.00026 0.00018</div>
<br>
<p>Any idea for this discrepancy?</p>
<p><br>
</p>
<p>Thanks,</p>
<p>Brad<br>
</p>
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