Graphtyper enables population-scale genotyping using pangenome graphs
Graphtyper enables population-scale genotyping using pangenome graphs
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DOI：
10.1038/ng.3964
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发表时间：
2017-11-01
期刊：
影响因子：
30.8
通讯作者：
Halldorsson, Bjarni V.
中科院分区：
文献类型：
--
作者：
Eggertsson, Hannes P.;Jonsson, Hakon;Halldorsson, Bjarni V.
遗传研究的基本要求是准确确定序列变异。虽然人类基因组序列多样性的特征日益明确，但仍需要有效的方法在序列分析中使用这些知识。在这里，我们介绍 Graphtyper，这是一种公开可用的新颖算法和软件，用于发现序列变异和进行基因分型。 Graphtyper 将短读序列数据重新对齐到泛基因组，这是一种变异感知图结构，通过将可能的单倍型表示为图路径来编码群体内的序列变异。我们的结果表明 Graphtyper 速度快、高度可扩展，并提供敏感且准确的基因型识别。 Graphtyper 使用不到 100,000 个 CPU 天对 28,075 名冰岛人的整个基因组中的 8940 万个序列变异进行了基因分型，其中包括 6 个人类白细胞抗原 (HLA) 基因的详细基因分型。我们证明，Graphtyper 是在小型和群体规模测序研究中表征序列变异的一个有价值的工具。
A fundamental requirement for genetic studies is an accurate determination of sequence variation. While human genome sequence diversity is increasingly well characterized, there is a need for efficient ways to use this knowledge in sequence analysis. Here we present Graphtyper, a publicly available novel algorithm and software for discovering and genotyping sequence variants. Graphtyper realigns shortread sequence data to a pangenome, a variation-aware graph structure that encodes sequence variation within a population by representing possible haplotypes as graph paths. Our results show that Graphtyper is fast, highly scalable, and provides sensitive and accurate genotype calls. Graphtyper genotyped 89.4 million sequence variants in the whole genomes of 28,075 Icelanders using less than 100,000 CPU days, including detailed genotyping of six human leukocyte antigen (HLA) genes. We show that Graphtyper is a valuable tool in characterizing sequence variation in both small and population-scale sequencing studies.