A method for identifying metagenomic species and variable genetic elements by exhaustive co-abundance binning

The microbial diversity of environments like the human gut extends far beyond what is covered by reference genomes. Here we present a method for exhaustive and unsupervised co-abundance gene binning across a series of highly complex metagenomic samples. As the method does not rely on previously sequenced reference genomes it allows for discovery of new species, viruses and clonal heterogeneity. We demonstrate the method on human gut microbiome data and identify 7,381 co-abundance gene groups (CAGs) ranging in size from 3 to 6,319 genes. The CAGs represent a wide variety of biological entities including microbial genomes, phages and clonal differences. We name the 741 largest of these metagenomic species (MGS), because they correspond to microbial species. In addition, we establish microbial host affiliations by dependency-associations for many small CAGs. Longitudinal sampling in the same individuals indicates that some of these dependency-associations are important for the persistence of their microbial host

诸如人体肠道在内的环境中，微生物多样性远超参考基因组（reference genome）所能覆盖的范畴。本研究提出一种可针对一系列高度复杂宏基因组样本开展穷尽式无监督共丰度基因分箱（co-abundance gene binning）的方法。由于该方法无需依赖已测序的参考基因组，因此可用于发现新物种、病毒以及克隆异质性。本研究在人体肠道宏基因组数据集上验证了该方法，共鉴定出7381个共丰度基因簇（co-abundance gene groups, CAGs），其基因数量范围为3至6319个。这些共丰度基因簇涵盖了多种生物实体，包括微生物基因组、噬菌体（phage）以及克隆差异特征。我们将其中规模最大的741个归类为宏基因组物种（metagenomic species, MGS），因其与微生物物种一一对应。此外，我们通过依赖关联关系为众多小型共丰度基因簇确定了微生物宿主归属。对同一受试者的纵向采样分析表明，部分此类依赖关联对于其微生物宿主的持续定植至关重要。