Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah and School of Medicine, Salt Lake City, UT 84112, USA.
Genome Res. 2011 Sep;21(9):1529-42. doi: 10.1101/gr.123158.111. Epub 2011 Jun 23.
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.
VAAST（变体注释、分析和搜索工具）是一种用于在个人基因组序列中识别受损基因及其致病变体的概率搜索工具。VAAST 建立在现有的氨基酸取代 (AAS) 和聚集方法的基础上，用于变体优先级排序，将两者的元素结合到一个单一的统一似然框架中，使用户能够以更准确和易于使用的方式识别受损基因和有害变体。VAAST 可以对编码和非编码变体进行评分，同时评估这两种类型变体的累积影响。VAAST 可以识别导致罕见遗传疾病的罕见变体，也可以使用罕见和常见变体来识别导致常见疾病的基因。因此，VAAST 的使用范围比任何现有方法都要广泛得多。在这里，我们使用没有两个个体具有相同有害变体的小队列（n=3）来证明其识别受损基因的能力，并且使用多达 150 个病例来证明常见的多基因疾病。
