MetaGenomic Species (MGS:1427) from Distal Human Gut Microbiota (MetaHit), Sample O2.UC20-2. Eggerthella sp. CAG:1427

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（Metagenomic）数据极为复杂，缺乏明确的结构，且通常以未知物种为主导。我们采用丰度协方差策略，将高度共变异的基因聚类为宏基因组物种（MetaGenomic Species），这类实体涵盖了细菌基因组、质粒、基因组岛、克隆变异体以及噬菌体等多种生物单元。将这一思路应用于源自396份人类粪便样本的全新390万微生物基因集，我们共识别出7381个此类宏基因组物种。这些宏基因组物种的基因数量跨度为3至6319个，其中741个宏基因组物种的基因数量与细菌基因组规模相近。宏基因组物种在分类学与GC含量上表现出显著的一致性，其中247个宏基因组物种的组装结果甚至达到了人类微生物组计划（Human Microbiome Project，HMP）的高质量草图基因组标准。高达73%的宏基因组物种与任何已测序生物均无序列相似性。小型宏基因组物种富含噬菌体特征基因以及参与生物互作的重要功能基因，且与基因丰富型宏基因组物种存在显著的依赖关系。本研究首次实现了将高度复杂的宏基因组样本集无监督聚类为生物实体的结构化分析，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关系开展了全局性解析。