Inria Grenoble Rhône-Alpes, Montbonnot, France.
Université de Lyon, Université Lyon 1, CNRS, Laboratoire de Biométrie et Biologie Evolutive UMR 5558, Villeurbanne, France.
Nat Biotechnol. 2021 Apr;39(4):422-430. doi: 10.1038/s41587-020-00747-w. Epub 2020 Dec 14.
Generating accurate genome assemblies of large, repeat-rich human genomes has proved difficult using only long, error-prone reads, and most human genomes assembled from long reads add accurate short reads to polish the consensus sequence. Here we report an algorithm for hybrid assembly, WENGAN, that provides very high quality at low computational cost. We demonstrate de novo assembly of four human genomes using a combination of sequencing data generated on ONT PromethION, PacBio Sequel, Illumina and MGI technology. WENGAN implements efficient algorithms to improve assembly contiguity as well as consensus quality. The resulting genome assemblies have high contiguity (contig NG50: 17.24-80.64 Mb), few assembly errors (contig NGA50: 11.8-59.59 Mb), good consensus quality (QV: 27.84-42.88) and high gene completeness (BUSCO complete: 94.6-95.2%), while consuming low computational resources (CPU hours: 187-1,200). In particular, the WENGAN assembly of the haploid CHM13 sample achieved a contig NG50 of 80.64 Mb (NGA50: 59.59 Mb), which surpasses the contiguity of the current human reference genome (GRCh38 contig NG50: 57.88 Mb).
使用仅长且易错的reads 来生成大型、重复丰富的人类基因组的准确基因组组装一直很困难，大多数从长reads 组装的人类基因组会添加准确的短reads 来优化共识序列。在这里，我们报告了一种混合组装算法 WENGAN，该算法以低计算成本提供非常高质量的结果。我们使用 ONT PromethION、PacBio Sequel、Illumina 和 MGI 技术生成的测序数据组合，展示了对四个人类基因组的从头组装。WENGAN 实现了高效的算法，以提高组装连续性和共识质量。生成的基因组组装具有高连续性（contig NG50：17.24-80.64 Mb）、很少的组装错误（contig NGA50：11.8-59.59 Mb）、良好的共识质量（QV：27.84-42.88）和高基因完整性（BUSCO 完整：94.6-95.2%），同时消耗低计算资源（CPU 小时：187-1200）。特别是，WENGAN 对单体型 CHM13 样本的组装实现了 80.64 Mb 的 contig NG50（NGA50：59.59 Mb），超过了当前人类参考基因组（GRCh38 contig NG50：57.88 Mb）的连续性。
