MetaGenomic Species (MGS:226) from Distal Human Gut Microbiota (MetaHit), Sample MH0012. Clostridium sp. CAG:226

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.

通过深度测序获取的宏基因组数据（Metagenomic data）复杂度极高，缺乏明确的结构特征，且通常以未知物种占主导。本研究采用丰度共变异策略（abundance co-variance strategy），将高度共变异的基因聚类为宏基因组物种（MetaGenomic Species），该类单元涵盖了多样的生物学实体：包括细菌基因组、质粒、基因组岛、克隆变异与噬菌体（bacteriophages）。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，共鉴定得到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，其中741个宏基因组物种的基因数量与典型细菌基因组的基因数量相近。宏基因组物种在分类学特征与GC含量（GC content）上均呈现出显著的一致性，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）高质量草图基因组标准。高达73%的宏基因组物种与任何已完成测序的生物体均未检测到序列相似性。基因数量较少的宏基因组物种富集有噬菌体特征基因，以及参与生物互作的关键功能基因，且与基因丰富度较高的宏基因组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生物学实体，并对人类远端肠道内细菌、质粒、噬菌体以及基因组岛之间的遗传互作关系进行了全局性分析。