Divine: Prioritizing Genes for Rare Mendelian Disease in Whole Exome Sequencing Data

MotivationRecent studies showed that a phenotype-driven analysis of whole exome sequencing (WES) could provide more accurate and clinically relevant genetic variants.ResultsWe develop a computational tool called Divine that integrates patients’ phenotype(s) and WES data with 30 prior biological knowledge (e.g., human phenotype ontology, gene ontology, pathway database, protein-protein interaction networks, pathogenicity by the amino acid change due to polymorphism, and hot-spot protein domains) to prioritize potential disease-causing genes. In a retrospective study with 22 real and four simulated data set, Divine ranks the same pathogenic genes confirmed by the original studies 5th on average out of a thousand of mutated genes and outperforms existing state-of-the-art methods.Availabilityhttps://github.com/hwanglab/divineContacthwangt@ccf.orgSupplementary informationSupplementary Document is attached at the end of the page.