Detecting Novel Structural Variants In Genomes By Leveraging Parent-Child Relatedness
Detecting Novel Structural Variants In Genomes By Leveraging Parent-Child Relatedness
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DOI：
10.1109/bibm.2018.8621488
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发表时间：
2018-12
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影响因子：
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通讯作者：
M. Spence;Mario Banuelos;Roummel F. Marcia;Suzanne S. Sindi
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作者：
M. Spence;Mario Banuelos;Roummel F. Marcia;Suzanne S. Sindi
由相同物种的成员共享的长于单个核苷酸的基因组变异通常被称为结构变异（SV）。虽然相对罕见，但它们代表了越来越重要的一类变异，因为SV与疾病和对某些类型癌症的易感性有关。SV检测的常见方法需要将测试基因组的片段测序和作图到高质量的参考基因组。候选SV对应于具有不一致的映射构型的片段，但是因为测序和映射中的错误也会产生不一致的排列，所以这些预测中的许多将是错误的。当测序覆盖率低时，区分真正的SV与错误甚至更加复杂。在最近的工作中，我们已经开发出SV检测方法，同时考虑密切相关的个人-父母和孩子的基因组。我们的方法通过要求孩子从父母那里继承他们基因组中的所有SV来控制假阳性SV。然而，在这样做的时候，我们可能会错过孩子获得的真正的新变体。在这项工作中，我们概括了我们以前的方法，允许孩子携带新的变体，但通过l1惩罚执行稀疏性（因为孩子中的新SV应该是罕见的）。我们目前的结果都模拟基因组以及两个测序的亲子三人组从1000个基因组计划。
Genomic variation shared by members of the same species that are longer than a single nucleotide are commonly called structural variants (SVs). Though relatively rare, they represent an increasingly important class of variation as SVs have been associated with diseases and susceptibility to some types of cancer. Common approaches to SV detection require the sequencing and mapping of fragments from a test genome to a high-quality reference genome. Candidate SVs correspond to fragments with discordant mapped configurations, but because errors in the sequencing and mapping will also create discordant arrangements, many of these predictions will be false. When sequencing coverage is low, distinguishing true SVs from errors is even more complicated. In recent work, we have developed SV detection methods that simultaneously consider the genomes of closely related individuals – parents and children. Our approaches control false positive SVs by requiring children inherit all SVs in their genome from a parent. However, in doing so we may have missed true novel variants acquired by the child. In this work, we generalize our previous approaches to allow the child to carry novel variants but enforce sparsity through an l1 penalty (since novel SVs in the child should be rare). We present results on both simulated genomes as well as two-sequenced parent-child trios from the 1000 Genomes Project.