Variant Annotation, Analysis and Search Tool - VAAST 2

VAAST 2 (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 2 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 2 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 2 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 2 thus has a much greater scope of use than any existing methodology to prioritize candidate disease genes in sets of unlreated affected genome sequences.

Pedigree VAAST - pVAAST

High-throughput sequencing of related individuals has become an important tool for studying human disease. However, owing to technical complexity and lack of available tools, most pedigree-based sequencing studies rely on an ad hoc combination of suboptimal analyses. Pedigree-VAAST (pVAAST) is a disease-gene identification tool designed for high-throughput sequence data in pedigrees. pVAAST uses a sequence-based model to perform variant and gene-based linkage analysis. Linkage information is then combined with functional prediction and rare variant case-control association information in a unified statistical framework. The approach is robust to incomplete penetrance and locus heterogeneity and is applicable to a wide variety of genetic traits. pVAAST maintains high power across studies of monogenic, high-penetrance phenotypes in a single pedigree to highly polygenic, common phenotypes involving hundreds of pedigrees.

The VAAST package consists of four primary tools:

Note that another tool with the name VAT and similar functionality to VAAST's VAT was published recently by the Gerstein lab. You can access the Gerstein lab VAT on their web-site, however it's output is not compatible with VAAST 2.

Publications

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.
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
Manuck TA Watkins WS Moore B Esplin MS Varner MW Jackson GM Yandell M Jorde L
Am J Obstet Gynecol. 2014 Apr;210(4)
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.
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
Yandell M Huff CD Hu H Singleton M Moore B Xing J Jorde L Reese MG
Genome Res. 2011 Jul
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

Press

License & Downloads

VAAST/pVAAST is developed as a collaboration between the Yandell Lab at the University of Utah, the Huff Lab at MD Anderson Cancer Center and Omicia, Inc. of Oakland, CA. The University of Utah freely licenses VAAST 2 for academic research use. For commercial, clinical and all other uses please contact Martin Reese at Omicia, Inc.

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