Document Type

Article

Publication Date

5-20-2022

Publication Title

Briefings in bioinformatics

Keywords

JGM

JAX Source

Brief Bioinform 2022 May 20:bbac188

ISSN

1477-4054

PMID

35595299

DOI

https://doi.org/10.1093/bib/bbac188

Abstract

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.

Comments

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License.

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