MetaGenomic Species (MGS:14) from Distal Human Gut Microbiota (MetaHit), Sample MH0012. Odoribacter splanchnicus CAG:14 strain:MGS:14

Metagenomic data acquired by deep sequencing is immensely complex, lacks apparent structure and is typically dominated by unknown species. Using an abundance co-variance strategy, we group highly co-varying genes into MetaGenomic Species, which represent a wide range of biological entities: bacterial genomes, plasmids, genomic islands, clonal variation and bacteriophages. Applying this concept to a new 3.9 million microbial gene catalogue derived from 396 human stool samples we identified 7,381 such MetaGenomic Species. They range in size from 3 to 6,319 genes, with 741 MetaGenomic Species resembling bacterial genomes in number of genes contained. The Meta-Genomic Species displays remarkable consistency in taxonomy and GC content. 247 of the MetaGenomic Species assemblies even pass the HMP high quality draft genome criteria. A large proportion (73%) of the MetaGenomic Species displays no sequence similarity to any previously sequenced organism. Smaller MetaGenomic Species are enriched for genes characteristic for bacteriophages and functions important for biotic interactions and show strong dependencies to gene-rich MetaGenomic Species. We present the first unsupervised structuring of a highly complex series of metagenomic samples into biological entities, including a global analysis of the genetic interdependencies between bacteria, plasmids, phages and genetic islands in the human distal gut.

通过深度测序获得的宏基因组数据（Metagenomic data）复杂度极高，缺乏明确的结构特征，且样本中绝大多数为未知物种。本研究采用丰度共变异策略，将高度共变异的基因聚类为宏基因物种（MetaGenomic Species），这类实体涵盖了多种生物类群：细菌基因组、质粒、基因组岛、克隆变异体以及噬菌体。我们将这一分析框架应用于由396份人类粪便样本构建的全新390万微生物基因目录，共鉴定出7381个宏基因物种。这些宏基因物种所含基因数的跨度为3至6319个，其中741个宏基因物种的基因数量与细菌基因组规模相当。宏基因物种在分类学属性与GC含量（GC content）上表现出显著的一致性。其中247个宏基因物种的组装结果甚至符合人类微生物组计划（Human Microbiome Project, HMP）的高质量草图基因组标准。73%的宏基因物种与已完成测序的任何生物体均无序列相似性。小型宏基因物种显著富集噬菌体特征基因以及参与生物互作的功能基因，且与基因丰度较高的宏基因物种存在较强的依赖关系。本研究首次实现了将高度复杂的宏基因组样本集无监督结构化划分为独立生物实体，并对人类远端肠道内细菌、质粒、噬菌体与基因组岛之间的遗传互作开展了全局性分析。