Whole-exome sequencing (WES) has been enormously successful in the identification of novel Mendelian disease–associated genes. An individual exome typically harbors over 30,000 variants compared with the genomic reference sequence, and up to roughly 10,000 of them can be filtered but additional methods are needed to predict the variants that may have serious functional con-sequences. The authors of an article published in Nature Protocol describe a protocol for the Exomiser suite that uses clinical data, model organism phenotype data, as well as random-walk analysis of protein interactome data for novel disease-gene discovery or for differential diagnostics of Mendelian disease.
The Exomiser has been used in a number of projects for disease-gene discovery and diagnostics such as the US National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) as well as PhenomeCentral portal. The inputs to Exomiser are the called variants resulting from exome sequencing are stored using a variant call format (VCF) file. The Exomiser analyzes these VCF files to first filter the variants and then to prioritize the remaining candidates. The article provides a detailed explanation of the data sources utilized by Exomiser, which includes human and animal data sources integrated into algorithm, to priorities exome sequences
According to the authors, Exomiser requires ~3 GB of RAM and roughly 15–90 s of computing time on a standard desktop computer to analyze a variant call format (VCF) file and can be safely used within hospital firewalls. Exomiser is freely available for academic use from http://www.sanger.ac.uk/science/tools/exomiser.
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