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Phenotype-aware prioritisation of rare Mendelian disease variants.

ABSTRACT: A molecular diagnosis from the analysis of sequencing data in rare Mendelian diseases has a huge impact on the management of patients and their families. Numerous patient phenotype-aware variant prioritisation (VP) tools have been developed to help automate this process, and shorten the diagnostic odyssey, but performance statistics on real patient data are limited. Here we identify, assess, and compare the performance of all up-to-date, freely available, and programmatically accessible tools using a whole-exome, retinal disease dataset from 134 individuals with a molecular diagnosis. All tools were able to identify around two-thirds of the genetic diagnoses as the top-ranked candidate, with LIRICAL performing best overall. Finally, we discuss the challenges to overcome most cases remaining undiagnosed after current, state-of-the-art practices.

SUBMITTER: Kelly C

PROVIDER: S-EPMC9950798 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Phenotype-aware prioritisation of rare Mendelian disease variants.

Kelly Catherine C Szabo Anita A Pontikos Nikolas N Arno Gavin G Robinson Peter N PN Jacobsen Jules O B JOB Smedley Damian D Cipriani Valentina V

Trends in genetics : TIG 20220804 12

A molecular diagnosis from the analysis of sequencing data in rare Mendelian diseases has a huge impact on the management of patients and their families. Numerous patient phenotype-aware variant prioritisation (VP) tools have been developed to help automate this process, and shorten the diagnostic odyssey, but performance statistics on real patient data are limited. Here we identify, assess, and compare the performance of all up-to-date, freely available, and programmatically accessible tools us ...[more]

PMID: 35934592

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