美国国立卫生研究院Mikhail Kolmogorov等研究人员合作开发出新方法Strainy，可从长读长宏基因组测序中进行菌株单倍型的分相和组装。2024年9月26日，国际知名学术期刊《自然—方法学》在线发表了这一成果。

研究人员提出了Strainy，这是一种基于Nanopore和PacBio测序的菌株级宏基因组组装和分相算法。Strainy以去 novo宏基因组组装结果作为输入，识别菌株变异，然后将其分相并组装成连续的单倍型。

通过模拟和模拟的Nanopore及PacBio宏基因组数据，研究人员显示Strainy能够组装出准确且完整的菌株单倍型，优于当前基于Nanopore的方法，并在完整性和准确性上与基于PacBio的算法相当。随后，研究人员使用Strainy组装了复杂环境宏基因组的菌株单倍型，进而揭示了细菌物种中不同菌株的分布和突变模式。

据悉，微生物群落中的细菌物种通常由菌株混合组成，这些菌株在基因组上存在小的变异。短读长方法可以检测菌株间的小规模变异，但无法将这些变异分相成连续的单倍型。长读长宏基因组组装工具可以生成连续的细菌染色体，但常常为了物种水平的一致性而抑制菌株水平的变异。

附：英文原文

Title: Strainy: phasing and assembly of strain haplotypes from long-read metagenome sequencing

Author: Kazantseva, Ekaterina, Donmez, Ataberk, Frolova, Maria, Pop, Mihai, Kolmogorov, Mikhail

Issue&Volume: 2024-09-26

Abstract: Bacterial species in microbial communities are often represented by mixtures of strains, distinguished by small variations in their genomes. Short-read approaches can be used to detect small-scale variation between strains but fail to phase these variants into contiguous haplotypes. Long-read metagenome assemblers can generate contiguous bacterial chromosomes but often suppress strain-level variation in favor of species-level consensus. Here we present Strainy, an algorithm for strain-level metagenome assembly and phasing from Nanopore and PacBio reads. Strainy takes a de novo metagenomic assembly as input and identifies strain variants, which are then phased and assembled into contiguous haplotypes. Using simulated and mock Nanopore and PacBio metagenome data, we show that Strainy assembles accurate and complete strain haplotypes, outperforming current Nanopore-based methods and comparable with PacBio-based algorithms in completeness and accuracy. We then use Strainy to assemble strain haplotypes of a complex environmental metagenome, revealing distinct strain distribution and mutational patterns in bacterial species.

DOI: 10.1038/s41592-024-02424-1

Source: https://www.nature.com/articles/s41592-024-02424-1