Structural variant detection across sequencing technologies.

IF 44.5 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2026-10-15 DOI:10.1038/s41587-026-03332-9

Gaoyang Li, Yadong Liu, Anqi Zhang, Xiaoyi Lin, Zheng Hu, Bo Liu, Long Qian, Yadong Wang

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引用次数: 0

Abstract

Structural variants (SVs) are a major source of genomic diversity, yet their discovery remains challenging due to repetitive genomic contexts, alignment ambiguity and the trade-off between sequencing cost and read length. Here we introduce HitSV, which implements repetitiveness- and signature-density-aware breakpoint recognition coupled with precise haplotype-resolved local assembly, thereby enabling base-resolution SV reconstruction and genotyping in various sequencing technologies. On the HG002 benchmark, HitSV achieved 15-72% (long read), 10-36% (short read) and 12% (hybrid sequencing), respectively, higher genotype F1 scores than state-of-the-art SV callers. Applied to the 1KGP phase 4 cohort, HitSV expanded the SV callset by 31.5%, substantially reshaping allele-frequency landscapes. In a large Chinese long-read cohort, HitSV uncovered tandem-repeat-mobile-element composite arrays as a prevalent, multi-allelic class of complex SVs, highlighting composite repeat architectures as an important and previously underrecognized contributor to human structural variation.

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跨测序技术的结构变异检测。

结构变异（SVs）是基因组多样性的主要来源，但由于重复的基因组背景、比对模糊以及测序成本和读取长度之间的权衡，它们的发现仍然具有挑战性。在这里，我们介绍了HitSV，它实现了重复性和特征密度感知的断点识别，加上精确的单倍型分解的局部组装，从而实现了碱基分辨率的SV重建和各种测序技术的基因分型。在HG002基准上，HitSV分别达到15-72%（长读），10-36%（短读）和12%（杂交测序），比最先进的SV呼叫者更高的基因型F1得分。应用于1KGP 4期队列，HitSV将SV呼叫集扩展了31.5%，极大地重塑了等位基因频率格局。在一个大型的中国长读队列中，HitSV发现串联重复-移动元素复合阵列是一种普遍存在的多等位基因的复杂sv，强调复合重复结构是人类结构变异的重要贡献者，但以前未被认识到。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

期刊介绍： Nature Biotechnology is a monthly journal that focuses on the science and business of biotechnology. It covers a wide range of topics including technology/methodology advancements in the biological, biomedical, agricultural, and environmental sciences. The journal also explores the commercial, political, ethical, legal, and societal aspects of this research. The journal serves researchers by providing peer-reviewed research papers in the field of biotechnology. It also serves the business community by delivering news about research developments. This approach ensures that both the scientific and business communities are well-informed and able to stay up-to-date on the latest advancements and opportunities in the field. Some key areas of interest in which the journal actively seeks research papers include molecular engineering of nucleic acids and proteins, molecular therapy, large-scale biology, computational biology, regenerative medicine, imaging technology, analytical biotechnology, applied immunology, food and agricultural biotechnology, and environmental biotechnology. In summary, Nature Biotechnology is a comprehensive journal that covers both the scientific and business aspects of biotechnology. It strives to provide researchers with valuable research papers and news while also delivering important scientific advancements to the business community.