小柯机器人

美国国立卫生研究院Sergey Koren和Adam M. Phillippy共同合作，近期取得重要工作进展。他们研究利用Verkko实现了二倍染色体组的telomere-to-telomere组装。相关研究成果2023年2月16日在线出版于《自然—生物技术》杂志上。

据介绍，Telomere-to-Telomere联合体最近组装了第一个真正完整的人类基因组序列。为了解决最复杂的重复，该项目依赖于将超长牛津纳米孔测序reads与由长而准确的PacBio高保真reads构建的高分辨率组装图进行人工集成。

研究人员在Verkko中改进并自动化了这一策略，Verkko是一种基于图形的迭代流水线，用于组装完整的二倍体基因组。Verkko从一个由长、准确读数构建的多重de Bruijn图开始，并通过整合超长读数和单倍型特异性标记逐步简化该图。结果是两种单倍型的阶段性二倍体组装，许多染色体从端粒自动组装到端粒。在HG002人类基因组上运行Verkko导致46条二倍体染色体中的20条无缝隙组装，准确率为99.9997%。

总之，二倍体基因组的完整组装是构建全面的泛基因组数据库和染色体规模比较基因组学的关键一步。

附：英文原文

Title: Telomere-to-telomere assembly of diploid chromosomes with Verkko

Author: Rautiainen, Mikko, Nurk, Sergey, Walenz, Brian P., Logsdon, Glennis A., Porubsky, David, Rhie, Arang, Eichler, Evan E., Phillippy, Adam M., Koren, Sergey

Issue&Volume: 2023-02-16

Abstract: The Telomere-to-Telomere consortium recently assembled the first truly complete sequence of a human genome. To resolve the most complex repeats, this project relied on manual integration of ultra-long Oxford Nanopore sequencing reads with a high-resolution assembly graph built from long, accurate PacBio high-fidelity reads. We have improved and automated this strategy in Verkko, an iterative, graph-based pipeline for assembling complete, diploid genomes. Verkko begins with a multiplex de Bruijn graph built from long, accurate reads and progressively simplifies this graph by integrating ultra-long reads and haplotype-specific markers. The result is a phased, diploid assembly of both haplotypes, with many chromosomes automatically assembled from telomere to telomere. Running Verkko on the HG002 human genome resulted in 20 of 46 diploid chromosomes assembled without gaps at 99.9997% accuracy. The complete assembly of diploid genomes is a critical step towards the construction of comprehensive pangenome databases and chromosome-scale comparative genomics.

DOI: 10.1038/s41587-023-01662-6

Source: https://www.nature.com/articles/s41587-023-01662-6

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex