SVDSS: structural variation discovery in hard-to-call genomic regions using sample-specific strings from accurate long reads
SVDSS: structural variation discovery in hard-to-call genomic regions using sample-specific strings from accurate long reads
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DOI：
10.1038/s41592-022-01674-1
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发表时间：
2022-12-22
期刊：
影响因子：
48
通讯作者：
Chikhi, Rayan
中科院分区：
文献类型：
--
作者：
Denti, Luca;Khorsand, Parsoa;Chikhi, Rayan
结构变异（SVs）在人类基因组学和精准医学中发挥着重要作用。尽管多年来付出了巨大的努力，但由于人类基因组的二倍体和高度重复的结构，以及sv的存在大大超过测序读取长度，在个体中发现sv仍然具有挑战性。然而，最近引入的低误差长读测序技术，如PacBio HiFi，可能最终使这些障碍得以克服。在这里，我们提出了用样本特定字符串（SVDSS）发现SV的方法，这是一种从长读测序技术（例如PacBio HiFi）中发现SV的方法，它结合并有效地利用了无映射、基于映射和基于装配的方法，从而实现了整体优越的SV发现性能。我们在几个人类样本上的实验表明，SVDSS在发现PacBio HiFi读取中的插入和删除SVs方面优于最先进的基于定位的方法，并且在调用基因组重复区域的SVs方面取得了显着改进。
Structural variants (SVs) account for a large amount of sequence variability across genomes and play an important role in human genomics and precision medicine. Despite intense efforts over the years, the discovery of SVs in individuals remains challenging due to the diploid and highly repetitive structure of the human genome, and by the presence of SVs that vastly exceed sequencing read lengths. However, the recent introduction of low-error long-read sequencing technologies such as PacBio HiFi may finally enable these barriers to be overcome. Here we present SV discovery with sample-specific strings (SVDSS)-a method for discovery of SVs from long-read sequencing technologies (for example, PacBio HiFi) that combines and effectively leverages mapping-free, mapping-based and assembly-based methodologies for overall superior SV discovery performance. Our experiments on several human samples show that SVDSS outperforms state-of-the-art mapping-based methods for discovery of insertion and deletion SVs in PacBio HiFi reads and achieves notable improvements in calling SVs in repetitive regions of the genome.