Trends in genetics : TIG
JGM, Humans, Phenotype, Exome, Exome Sequencing, Rare Diseases
Trends Genet. 2022;38(12):1271-83
This study was supported by the National Institutes of Health (NIH) grants 1R24OD011883, U54 HG006370, and NIH, National Institute of Child Health and Human Development 1R01HD103805-01.
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.
Phenotype-aware prioritisation of rare Mendelian disease variants. Trends Genet. 2022;38(12):1271-83
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).