Variant Annotation, Analysis and Search Tool - VAAST

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 upon existing phylogenetic conservation, amino acid substitution (AAS) and aggregative approaches to variant prioritization, combining elements of all 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 (SNV, indel and splice site) and non-coding variants (SNV), 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 to prioritize candidate disease genes in sets of unlreated affected genome sequences.

Publications

A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data.
Hu H Roach JC Coon H Guthery SL Voelkerding KV Margraf RL Durtschi JD Tavtigian SV Shankaracharya Wu W Scheet P Wang S Xing J Glusman G Hubley R Li H Garg V Moore B Hood L Galas DJ Srivastava D Reese MG Jorde LB Yandell M Huff CD
Nature Biotech.
Using VAAST to Identify Disease-Associated Variants in Next-Generation Sequencing Data.
Kennedy B Kronenberg Z Hu H Moore B Flygare S Reese MG Jorde LB Yandell M Huff C
Current Protocols in Human Genetics. 2014 Apr 24;81:6.14.1-6.14.25
Pharmacogenomics of 17-alpha hydroxyprogesterone caproate for recurrent preterm birth prevention.
Manuck TA Watkins WS Moore B Esplin MS Varner MW Jackson GM Yandell M Jorde L
Am J Obstet Gynecol. 2014 Apr;210(4)
VAAST 2.0: improved variant classification and disease-gene identification using a conservation-controlled amino acid substitution matrix.
Hu H Huff CD Moore B Flygare S Reese MG Yandell M
Genet Epidemiol. 2013 37(6):622-34.
Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ
Shirley MD Tang H Gallione CJ Baugher JD Frelin LP Cohen B North PE Marchuk DA Comi AM Pevsner J
N Engl J Med. 2013 May 23;368(21):1971-9.
Genomic Diversity and Evolution of the Head Crest in the Rock Pigeon
Shapiro MD, Kronenberg Z, Li C, Domyan ET, Pan H, Campbell M, Tan H, Huff CD, Hu H, Vickrey AI, Nielsen SCA, Stringham SA, Hu H, Willerslev E, Gilbert MTP, Yandell M, Zhang G, Wang J.
Science. 2013 Mar 1;339(6123):1063-7
A probabilistic disease-gene finder for personal genomes
Yandell M Huff CD Hu H Singleton M Moore B Xing J Jorde L Reese MG
Genome Res. 2011 Jul
Using VAAST to Identify an X-Linked Disorder Resulting in Lethality in Male Infants Due to N-Terminal Acetyltransferase Deficiency
Rope AF Wang K Evjenth R Xing J Johnston JJ Swensen JJ Johnson WJ Moore B Huff CD Bird LM Carey JC Opitz JM Stevens CA Jiang T Schank C Fain HD Robison R Dalley B Chin S South ST Pysher TJ Jorde LB Hakonarson H Lillehaug JR Biesecker LG Yandell M Arnesen T Lyon GJ
Am J Hum Genet. 2011 Jul 15;89(1):28-43