Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications.
Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications.
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DOI：
10.1038/ng.3036
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发表时间：
2014-08
期刊：
影响因子：
30.8
通讯作者：
Lunter G
中科院分区：
文献类型：
--
作者：
Rimmer A;Phan H;Mathieson I;Iqbal Z;Twigg SRF;WGS500 Consortium;Wilkie AOM;McVean G;Lunter G
高通量DNA测序技术已经改变了遗传学研究，并开始对临床实践产生影响。然而，分析高通量测序数据仍然具有挑战性，特别是在准确性和周转时间至关重要的临床环境中。我们提出了一种新的方法来解决这个问题，在一个软件包中实现称为鸭嘴兽。鸭嘴兽通过使用局部从头组装产生候选变体，然后进行局部重新排列和概率单倍型估计，实现了对SNP、插入缺失和复杂多态性的高灵敏度和特异性。它比现有工具快一个数量级，并且无需预处理即可从原始对齐读取数据生成调用。我们通过与SAMtools和GATK在全基因组和外显子组捕获数据上进行比较，以高灵敏度和特异性识别15个亲子三重奏中的从头变异，以及通过估计人类白细胞抗原基因型，证明了鸭嘴兽在临床相关实验设计中的性能。直接从变异调用。
High-throughput DNA sequencing technology has transformed genetic research and is starting to make an impact on clinical practice. However, analyzing high-throughput sequencing data remains challenging, particularly in clinical settings where accuracy and turnaround times are critical. We present a new approach to this problem, implemented in a software package called Platypus. Platypus achieves high sensitivity and specificity for SNPs, indels and complex polymorphisms by using local de novo assembly to generate candidate variants, followed by local realignment and probabilistic haplotype estimation. It is an order of magnitude faster than existing tools and generates calls from raw aligned read data without preprocessing. We demonstrate the performance of Platypus in clinically relevant experimental designs by comparing with SAMtools and GATK on whole-genome and exome-capture data, by identifying de novo variation in 15 parent-offspring trios with high sensitivity and specificity, and by estimating human leukocyte antigen genotypes directly from variant calls.