College of Information and Computer Engineering, Northeast Forestry University, Harbin, 150040, China.
Brief Bioinform. 2022 Sep 20;23(5). doi: 10.1093/bib/bbac305.
High-quality genome chromosome-scale sequences provide an important basis for genomics downstream analysis, especially the construction of haplotype-resolved and complete genomes, which plays a key role in genome annotation, mutation detection, evolutionary analysis, gene function research, comparative genomics and other aspects. However, genome-wide short-read sequencing is difficult to produce a complete genome in the face of a complex genome with high duplication and multiple heterozygosity. The emergence of long-read sequencing technology has greatly improved the integrity of complex genome assembly. We review a variety of computational methods for complex genome assembly and describe in detail the theories, innovations and shortcomings of collapsed, semi-collapsed and uncollapsed assemblers based on long reads. Among the three methods, uncollapsed assembly is the most correct and complete way to represent genomes. In addition, genome assembly is closely related to haplotype reconstruction, that is uncollapsed assembly realizes haplotype reconstruction, and haplotype reconstruction promotes uncollapsed assembly. We hope that gapless, telomere-to-telomere and accurate assembly of complex genomes can be truly routinely achieved using only a simple process or a single tool in the future.
高质量的基因组染色体级别的序列为基因组学下游分析提供了重要基础，特别是单倍型解析和完整基因组的构建，这对基因组注释、突变检测、进化分析、基因功能研究、比较基因组学等方面都起着关键作用。然而，全基因组短读测序在面对具有高重复和多种杂合性的复杂基因组时，很难产生完整的基因组。长读测序技术的出现极大地提高了复杂基因组组装的完整性。我们综述了多种用于复杂基因组组装的计算方法，并详细描述了基于长读的崩溃、半崩溃和未崩溃组装器的理论、创新和缺点。在这三种方法中，未崩溃组装是最正确和完整的代表基因组的方法。此外，基因组组装与单倍型重构密切相关，即未崩溃组装实现了单倍型重构，而单倍型重构促进了未崩溃组装。我们希望未来仅通过简单的过程或单一工具，就能真正常规地实现复杂基因组的无缺口、端到端和精确组装。
