Aury Jean-Marc, Istace Benjamin
Génomique Métabolique, Genoscope, Institut François Jacob, CEA, CNRS, Univ Evry, Université Paris-Saclay, 91057 Evry, France.
NAR Genom Bioinform. 2021 May 3;3(2):lqab034. doi: 10.1093/nargab/lqab034. eCollection 2021 Jun.
Single-molecule sequencing technologies have recently been commercialized by Pacific Biosciences and Oxford Nanopore with the promise of sequencing long DNA fragments (kilobases to megabases order) and then, using efficient algorithms, provide high quality assemblies in terms of contiguity and completeness of repetitive regions. However, the error rate of long-read technologies is higher than that of short-read technologies. This has a direct consequence on the base quality of genome assemblies, particularly in coding regions where sequencing errors can disrupt the coding frame of genes. In the case of diploid genomes, the consensus of a given gene can be a mixture between the two haplotypes and can lead to premature stop codons. Several methods have been developed to polish genome assemblies using short reads and generally, they inspect the nucleotide one by one, and provide a correction for each nucleotide of the input assembly. As a result, these algorithms are not able to properly process diploid genomes and they typically switch from one haplotype to another. Herein we proposed Hapo-G (Haplotype-Aware Polishing Of Genomes), a new algorithm capable of incorporating phasing information from high-quality reads (short or long-reads) to polish genome assemblies and in particular assemblies of diploid and heterozygous genomes.
单分子测序技术最近已由太平洋生物科学公司和牛津纳米孔公司商业化，有望对长DNA片段（千碱基到兆碱基级别）进行测序，然后使用高效算法，在重复区域的连续性和完整性方面提供高质量的组装结果。然而，长读长技术的错误率高于短读长技术。这对基因组组装的碱基质量有直接影响，特别是在编码区域，测序错误可能会破坏基因的编码框架。对于二倍体基因组，给定基因的共有序列可能是两种单倍型的混合，可能导致过早的终止密码子。已经开发了几种使用短读长来优化基因组组装的方法，通常，它们逐个检查核苷酸，并对输入组装的每个核苷酸进行校正。因此，这些算法无法正确处理二倍体基因组，它们通常会从一种单倍型切换到另一种单倍型。在此，我们提出了Hapo-G（基因组单倍型感知优化），这是一种新算法，能够整合来自高质量读长（短读长或长读长）的定相信息，以优化基因组组装，特别是二倍体和杂合基因组的组装。
