The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool.
The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool.
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DOI：
10.1186/s12859-018-2056-y
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发表时间：
2018-02-20
影响因子：
3
通讯作者：
Yandell M
中科院分区：
文献类型：
--
作者：
Flygare S;Hernandez EJ;Phan L;Moore B;Li M;Fejes A;Hu H;Eilbeck K;Huff C;Jorde L;G Reese M;Yandell M
用于诊断和发现孟德尔疾病的序列变异的优先顺序具有挑战性，特别是在大量全基因组序列 (WGS) 中。发现研究、临床应用以及 dbSNP 和 gnomAD 等大规模公共变异存储库的管理需要快速、可扩展的解决方案。为此，我们开发了 VVP，即 VAAST 变体优先级排序器。 VVP 速度超快，甚至可以扩展到最大的变异存储库和基因组集合，其输出旨在简化对不确定意义的变异的临床解释。我们表明，使用具有 4 个 CPU 和 16 GB RAM 的机器，对 dbSNP（> 1.55 亿个变体）的全部内容进行评分仅需要 95 分钟，并且可以在不到 5 分钟的时间内处理 60X WGS。我们还证明，VVP 可以对基因组中任何位置的变异进行评分，无论类型、效应或位置如何。它通过整合序列保守性、序列变化的类型、等位基因频率、变异负担和接合性来实现这一点。最后，我们还表明，VVP 分数始终准确且易于解释，这是许多常用工具（例如 SIFT 和 CADD）所不具备的特征。 VVP 提供快速且可扩展的方法来优先考虑基因组中任何位置的任何序列变异，其评分旨在促进使用 ACMG 和 NHS 指南进行变异解释。这些特性使其非常适合对大量 WGS 序列进行操作。本文的在线版本 (10.1186/s12859-018-2056-y) 包含补充材料，可供授权用户使用。
Prioritization of sequence variants for diagnosis and discovery of Mendelian diseases is challenging, especially in large collections of whole genome sequences (WGS). Fast, scalable solutions are needed for discovery research, for clinical applications, and for curation of massive public variant repositories such as dbSNP and gnomAD. In response, we have developed VVP, the VAAST Variant Prioritizer. VVP is ultrafast, scales to even the largest variant repositories and genome collections, and its outputs are designed to simplify clinical interpretation of variants of uncertain significance. We show that scoring the entire contents of dbSNP (> 155 million variants) requires only 95 min using a machine with 4 cpus and 16 GB of RAM, and that a 60X WGS can be processed in less than 5 min. We also demonstrate that VVP can score variants anywhere in the genome, regardless of type, effect, or location. It does so by integrating sequence conservation, the type of sequence change, allele frequencies, variant burden, and zygosity. Finally, we also show that VVP scores are consistently accurate, and easily interpreted, traits not shared by many commonly used tools such as SIFT and CADD. VVP provides rapid and scalable means to prioritize any sequence variant, anywhere in the genome, and its scores are designed to facilitate variant interpretation using ACMG and NHS guidelines. These traits make it well suited for operation on very large collections of WGS sequences. The online version of this article (10.1186/s12859-018-2056-y) contains supplementary material, which is available to authorized users.
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影响因子：
8.8
作者：
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DOI：
10.1073/pnas.89.22.10915
发表时间：
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