title: A probabilistic disease-gene finder for personal genomes.
abstract: VAAST (the Variant Annotation, Analysis & Search Tool) is a probabilistic search tool for identifying damaged genes and their disease-causing variants in personal genome sequences. VAAST builds on existing amino acid substitution (AAS) and aggregative approaches to variant prioritization, combining elements of both into a single unified likelihood framework that allows users to identify damaged genes and deleterious variants with greater accuracy, and in an easy-to-use fashion. VAAST can score both coding and noncoding variants, evaluating the cumulative impact of both types of variants simultaneously. VAAST can identify rare variants causing rare genetic diseases, and it can also use both rare and common variants to identify genes responsible for common diseases. VAAST thus has a much greater scope of use than any existing methodology. Here we demonstrate its ability to identify damaged genes using small cohorts (n = 3) of unrelated individuals, wherein no two share the same deleterious variants, and for common, multigenic diseases using as few as 150 cases.
authors.affiliation: Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah and School of Medicine, Salt Lake City, UT 84112, USA. myandell@genetics.utah.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Yandell
authors.forename: Chad
authors.initials: C
authors.lastname: Huff
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Marc
authors.initials: M
authors.lastname: Singleton
authors.forename: Barry
authors.initials: B
authors.lastname: Moore
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Xing
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Jorde
authors.forename: Martin G
authors.initials: MG
authors.lastname: Reese
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D019943:Amino Acid Substitution; D003967:Diarrhea / Q000151:congenital / Q000235:genetics; D005796:Genes; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics; D008342:Mandibulofacial Dysostosis / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000235:genetics; D008844:Micrognathism / Q000235:genetics; D020412:Multifactorial Inheritance / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D022661:RNA, Untranslated / Q000235:genetics; D012984:Software
chemical_list: D022661:RNA, Untranslated