{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:53:41Z","timestamp":1779306821925,"version":"3.51.4"},"reference-count":4,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R24OD011883"],"award-info":[{"award-number":["1R24OD011883"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 HG006370"],"award-info":[{"award-number":["U54 HG006370"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Yuan et\u00a0al. recently described an independent evaluation of several phenotype-driven gene prioritization methods for Mendelian disease on two separate, clinical datasets. Although they attempted to use default settings for each tool, we describe three key differences from those we currently recommend for our Exomiser and PhenIX tools. These influence how variant frequency, quality and predicted pathogenicity are used for filtering and prioritization. We propose that these differences account for much of the discrepancy in performance between that reported by them (15\u201326% diagnoses ranked top by Exomiser) and previously published reports by us and others (72\u201377%). On a set of 161 singleton samples, we show using these settings increases performance from 34% to 72% and suggest a reassessment of Exomiser and PhenIX on their datasets using these would show a similar uplift.<\/jats:p>","DOI":"10.1093\/bib\/bbac188","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T11:23:52Z","timestamp":1651058632000},"source":"Crossref","is-referenced-by-count":13,"title":["Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases"],"prefix":"10.1093","volume":"23","author":[{"given":"Julius O B","family":"Jacobsen","sequence":"first","affiliation":[{"name":"William Harvey Research Institute , Charterhouse Square, Barts and the London School of Medicine and Dentistry Queen, Queen Mary University of London, EC1M 6BQ London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Kelly","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute , Charterhouse Square, Barts and the London School of Medicine and Dentistry Queen, Queen Mary University of London, EC1M 6BQ London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Cipriani","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute , Charterhouse Square, Barts and the London School of Medicine and Dentistry Queen, Queen Mary University of London, EC1M 6BQ London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter N","family":"Robinson","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine , 10 Discovery Drive, Farmington, CT 06032 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-9850","authenticated-orcid":false,"given":"Damian","family":"Smedley","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute , Charterhouse Square, Barts and the London School of Medicine and Dentistry Queen, Queen Mary University of London, EC1M 6BQ London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"issue":"2","key":"2022092013195833200_ref1","doi-asserted-by":"crossref","DOI":"10.1093\/bib\/bbac019","article-title":"Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases","volume":"23","author":"Yuan","year":"2022","journal-title":"Brief Bioinform"},{"issue":"20","key":"2022092013195833200_ref2","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1056\/NEJMoa2035790","article-title":"100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report","volume":"385","author":"100,000 Genomes Project Pilot Investigators","year":"2021","journal-title":"N Engl J Med"},{"issue":"4","key":"2022092013195833200_ref3","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3390\/genes11040460","article-title":"An Improved Phenotype-Driven Tool for Rare Mendelian Variant Prioritization: Benchmarking Exomiser on Real Patient Whole-Exome Data","volume":"11","author":"Cipriani","year":"2020","journal-title":"Genes (Basel)"},{"issue":"2","key":"2022092013195833200_ref4","doi-asserted-by":"crossref","DOI":"10.1101\/mcs.a003756","article-title":"A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants","volume":"5","author":"Ji","year":"2019","journal-title":"Cold Spring Harb Mol Case Stud"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/23\/5\/bbac188\/45936920\/bbac188.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/23\/5\/bbac188\/45936920\/bbac188.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T17:24:14Z","timestamp":1663694654000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbac188\/6589867"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,20]]},"references-count":4,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,9,20]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbac188","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9]]},"published":{"date-parts":[[2022,5,20]]},"article-number":"bbac188"}}