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Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases

Yuan et al. 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 recommen...

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Autores principales: Jacobsen, Julius O B, Kelly, Catherine, Cipriani, Valentina, Robinson, Peter N, Smedley, Damian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487604/
https://www.ncbi.nlm.nih.gov/pubmed/35595299
http://dx.doi.org/10.1093/bib/bbac188
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author Jacobsen, Julius O B
Kelly, Catherine
Cipriani, Valentina
Robinson, Peter N
Smedley, Damian
author_facet Jacobsen, Julius O B
Kelly, Catherine
Cipriani, Valentina
Robinson, Peter N
Smedley, Damian
author_sort Jacobsen, Julius O B
collection PubMed
description Yuan et al. 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 (15–26% diagnoses ranked top by Exomiser) and previously published reports by us and others (72–77%). 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.
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spelling pubmed-94876042022-09-21 Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases Jacobsen, Julius O B Kelly, Catherine Cipriani, Valentina Robinson, Peter N Smedley, Damian Brief Bioinform Letter to Editor Yuan et al. 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 (15–26% diagnoses ranked top by Exomiser) and previously published reports by us and others (72–77%). 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. Oxford University Press 2022-05-20 /pmc/articles/PMC9487604/ /pubmed/35595299 http://dx.doi.org/10.1093/bib/bbac188 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Letter to Editor
Jacobsen, Julius O B
Kelly, Catherine
Cipriani, Valentina
Robinson, Peter N
Smedley, Damian
Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases
title Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases
title_full Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases
title_fullStr Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases
title_full_unstemmed Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases
title_short Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases
title_sort evaluation of phenotype-driven gene prioritization methods for mendelian diseases
topic Letter to Editor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487604/
https://www.ncbi.nlm.nih.gov/pubmed/35595299
http://dx.doi.org/10.1093/bib/bbac188
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