HapCUT2: robust and accurate haplotype assembly for diverse sequencing technologies.
HapCUT2: robust and accurate haplotype assembly for diverse sequencing technologies.
复制标题
DOI：
10.1101/gr.213462.116
复制
发表时间：
2017-05
期刊：
影响因子：
7
通讯作者：
Bansal V
中科院分区：
文献类型：
--
作者：
Edge P;Bafna V;Bansal V
已经开发了许多用于单倍型组装的工具——使用映射到参考基因组序列的读数重建单个单倍型。由于对获得单倍型解析的人类基因组的兴趣日益浓厚，已经开发了一系列新的测序方案和技术来重建全基因组单倍型。然而，旨在处理特定技术的现有计算方法不能很好地适应来自不同协议的数据。我们描述了一种新算法 HapCUT2，它扩展了我们之前的方法 (HapCUT) 以处理多种测序技术。使用来自多种不同数据类型（稀释池测序、连锁读测序、单分子实时（SMRT）测序和邻位连接（Hi-C）测序）的模拟和全基因组测序（WGS）数据，我们表明HapCUT2能够快速组装单倍型，并且对于所有数据类型都具有一流的准确性。特别是，HapCUT2 可以很好地扩展高测序覆盖率，并为两个长读长 WGS 数据集快速组装单倍型，而其他方法在这方面表现不佳。此外，HapCUT2 直接对 Hi-C 特定错误模式进行建模，与 HapCUT 相比，错误率显着提高，HapCUT 是唯一可以从 Hi-C 数据组装单倍型的方法。使用 HapCUT2，从 90 倍覆盖率的全基因组 Hi-C 数据集进行单倍型组装，产生了高分辨率单倍型（78.6% 的变体定相在单个块中），具有高成对定相准确度（跨染色体约 98%）。我们的结果表明 HapCUT2 是一种强大的单倍型组装工具，适用于来自不同测序技术的数据。
Many tools have been developed for haplotype assembly—the reconstruction of individual haplotypes using reads mapped to a reference genome sequence. Due to increasing interest in obtaining haplotype-resolved human genomes, a range of new sequencing protocols and technologies have been developed to enable the reconstruction of whole-genome haplotypes. However, existing computational methods designed to handle specific technologies do not scale well on data from different protocols. We describe a new algorithm, HapCUT2, that extends our previous method (HapCUT) to handle multiple sequencing technologies. Using simulations and whole-genome sequencing (WGS) data from multiple different data types—dilution pool sequencing, linked-read sequencing, single molecule real-time (SMRT) sequencing, and proximity ligation (Hi-C) sequencing—we show that HapCUT2 rapidly assembles haplotypes with best-in-class accuracy for all data types. In particular, HapCUT2 scales well for high sequencing coverage and rapidly assembled haplotypes for two long-read WGS data sets on which other methods struggled. Further, HapCUT2 directly models Hi-C specific error modalities, resulting in significant improvements in error rates compared to HapCUT, the only other method that could assemble haplotypes from Hi-C data. Using HapCUT2, haplotype assembly from a 90× coverage whole-genome Hi-C data set yielded high-resolution haplotypes (78.6% of variants phased in a single block) with high pairwise phasing accuracy (∼98% across chromosomes). Our results demonstrate that HapCUT2 is a robust tool for haplotype assembly applicable to data from diverse sequencing technologies.