Targeted genotyping of variable number tandem repeats with adVNTR
Targeted genotyping of variable number tandem repeats with adVNTR
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DOI：
10.1101/gr.235119.118
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发表时间：
2018-11-01
期刊：
影响因子：
7
通讯作者：
Bafna, Vineet
中科院分区：
文献类型：
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作者：
Bakhtiari, Mehrdad;Shleizer-Burko, Sharona;Bafna, Vineet
全基因组测序越来越多地被用于识别临床管道中的孟德尔变异。这些管道专注于单核苷酸变体(SNV)和结构变体，而忽略了更复杂的重复序列变体。在这里，我们考虑了可变数目串联重复序列(VNTRs)的基因分型问题，该重复序列由短(6-100bp)重复单元的不精确串联复制组成。VNR跨越人类基因组的3%，经常存在于编码区，并与多种孟德尔疾病有关。尽管现有的工具识别VNTR携带的序列，但从全基因组测序读数中对VNTRs进行基因分型(确定重复单位数和序列变异)仍然具有挑战性。我们描述了一种方法advntr，它使用隐马尔可夫模型来建模每个vntr，计数重复单元，并检测序列变异。Advntr模型可用于短读(Illumina)和单分子(Pacific Biosciences[PacBio])全基因组和全外显子组测序，并在多个模拟和真实数据集上显示了良好的结果。
Whole-genome sequencing is increasingly used to identify Mendelian variants in clinical pipelines. These pipelines focus on single-nucleotide variants (SNVs) and also structural variants, while ignoring more complex repeat sequence variants. Here, we consider the problem of genotyping Variable Number Tandem Repeats (VNTRs), composed of inexact tandem duplications of short (6-100 bp) repeating units. VNTRs span 3% of the human genome, are frequently present in coding regions, and have been implicated in multiple Mendelian disorders. Although existing tools recognize VNTR carrying sequence, genotyping VNTRs (determining repeat unit count and sequence variation) from whole-genome sequencing reads remains challenging. We describe a method, adVNTR, that uses hidden Markov models to model each VNTR, count repeat units, and detect sequence variation. adVNTR models can be developed for short-read (Illumina) and single-molecule (Pacific Biosciences [PacBio]) whole-genome and whole-exome sequencing, and show good results on multiple simulated and real data sets.