混合宏基因组组装能够对人类微生物群落中的耐药性决定因素和移动元素进行高分辨率分析，这一成果由新加坡基因组研究所Niranjan Nagarajan团队取得。2019年8月出版的《自然—生物技术》杂志发表了这一最新研究成果。

研究组提出了一个名为OPERA-MS的混合宏基因组装配器，它将基于装配的宏基因组集群与重复感知相结合，以精确地组装复杂的架构。在体外和虚拟肠道微生物组中定义的评估结果表明，OPERA-MS组装的宏基因组具有比长读更高的碱基配对精确度 (>5×; Canu)， 比短读有更高的识别率（~10× NGA50; MEGAHIT, IDBA-UD, metaSPAdes），比非混合宏基因组装配器有更少的组装错误（2×; hybridSPAdes）。OPERA-MS在存在相同物种的多个基因组的情况下提供菌株解析装配，为稀有物种(< 1%)提供高质量的参考基因组，具有约9个长阅读覆盖范围，以及具有更高覆盖范围的接近完整的基因组。小组使用OPERA-MS组装了抗生素治疗患者的28个肠道亚基因组，并显示包含长纳米孔读数产生了FC碰碰胡老虎机法典-提高赢钱机率的下注技巧连续的装配体(比短读数装配体改进了200个)，包括80多个封闭质粒或噬菌体序列和一个新的263kbp巨型噬菌体。高质量的混合组件使精确地观察人类患者的肠道耐药性成为可能。

据介绍，通过高通量宏基因组测序已经实现了微生物组的表征。然而,现有的方法并不是为了结合长、短读技术所设计的。

附：英文原文

Title: Hybrid metagenomic assembly enables high-resolution analysis of resistance determinants and mobile elements in human microbiomes

Author: Denis Bertrand, Jim Shaw, Manesh Kalathiyappan, Amanda Hui Qi Ng, M. Senthil Kumar, Chenhao Li, Mirta Dvornicic, Janja Paliska Soldo, Jia Yu Koh, Chengxuan Tong, Oon Tek Ng, Timothy Barkham, Barnaby Young, Kalisvar Marimuthu, Kern Rei Chng, Mile Sikic, Niranjan Nagarajan

Issue&Volume: Volume 37 Issue 8

Abstract: Characterization of microbiomes has been enabled by high-throughput metagenomic sequencing. However, existing methods are not designed to combine reads from short- and long-read technologies. We present a hybrid metagenomic assembler named OPERA-MS that integrates assembly-based metagenome clustering with repeat-aware, exact scaffolding to accurately assemble complex communities. Evaluation using defined in vitro and virtual gut microbiomes revealed that OPERA-MS assembles metagenomes with greater base pair accuracy than long-read (>5; Canu), higher contiguity than short-read (~10 NGA50; MEGAHIT, IDBA-UD, metaSPAdes) and fewer assembly errors than non-metagenomic hybrid assemblers (2; hybridSPAdes). OPERA-MS provides strain-resolved assembly in the presence of multiple genomes of the same species, high-quality reference genomes for rare species (<1%) with ~9 long-read coverage and near-complete genomes with higher coverage. We used OPERA-MS to assemble 28 gut metagenomes of antibiotic-treated patients, and showed that the inclusion of long nanopore reads produces more contiguous assemblies (200 improvement over short-read assemblies), including more than 80 closed plasmid or phage sequences and a new 263kbp jumbo phage. High-quality hybrid assemblies enable an exquisitely detailed view of the gut resistome in human patients.

DOI: 10.1038/s41587-019-0191-2

Source:https://www.nature.com/articles/s41587-019-0191-2