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.
The VAAST 2 package consists of three primary tools:
- VAT. The Variant Annotation Tool calculates a rich set of annotations on the effects that variants have on genomic features based on terms described and constrained by the Sequence Ontology. These effects, like synonymous and missense changes, stop-gain and loss, splice site variants and others that provide additional information about the functional effect of a variant, which VAAST 2 uses to score features.
- VST. The Variant Selection Tool performs set operations (intersection, union, complement, and difference) on a group of annotated GVF files to produce a merged representation of the group's variants in a CDR file. VST can be used to simply create a merged set of variants for the target or background genomes required as input to VAAST 2, but can also manufacture arbitrarily complex selections based on nested set operations.
- VAAST 2. A probabilistic search tool that uses the outputs of VAT and VST to identify damaged genes and their disease-causing variants in personal genome sequences.