An evolution-based framework for describing human gut bacteria

The human gut microbiome contains many bacterial strains of the same species (‘strain-level variants’). Describing strains in a biologically meaningful manner rather than purely taxonomic objects is an important goal but challenging due to the complexity of strain-level variation. Here, we measured patterns of co-evolution across >7,000 strains spanning the bacterial tree-of-life. Using these patterns as a prior for studying hundreds of gut commensal strains that we isolated, sequenced, and metabolically profiled revealed widespread structure beneath the phylogenetic level of species. Defining strains by their co-evolutionary signatures enabled predicting their metabolic phenotypes and engineering consortia from strain genome content alone. Our findings demonstrate a biologically relevant organization to strain-level variation and motivate a new schema for describing bacterial strains based on their evolutionary history., Materials and Methods (futher details and metadata in associated article's supplementary material) Creating a bank of commensal human gut microbiome strains Fecal samples were obtained from 28 human donors that fell within the age range of 18 to 63 with a median age of 35. Donors were selected as those with no antibiotic use in the past year, no known history of diabetes, colitis, autoimmune disease, cancer, pneumonia, dysentery, or cellulitis at time of consent. Institutions that approved protocols of fecal sample collection were Memorial Sloan Kettering (MSK) and the University of Chicago. Fresh fecal samples were immediately reduced in an anaerobic chamber upon collection and diluted and cultured on various growth media. Agar media types vary, but include any of following: Columbia Blood Agar, Brain Heart Infusion +Yeast, Brain Heart Infusion + Mucin, Brain Heart Infusion + Yeast + Acetate or N-Acetylglucosamine, reinforced Clostridial Agar, Peptone Yeast Glucose, Yeast Casitone Fatt..., , # An evolution-based framework for describing human gut bacteria Extended Data for \"An evolution-based framework for describing human gut bacteria\". ## Description of the data and file structure **Data: xslx file** ·     **Panel A:** Data matrix of Orthologous Gene Groups (OGGs) annotations for each of the 669 strains in the Commensal Strain Bank. First column holds the unique ID for each strain. Subsequent columns hold the data for each OGG as listed in first row. Each value denotes the number of sequences from the strains coding regions that are mapped to that OGG (see methods). ·     **Panel B:** Projections of each of 669 strains onto the principal components describing co-evolutionary variation in UniProt (see methods). First column is the strain id, subsequent columns are for each of the 7047 principal components with each value denoting the contribution of strain *i* onto principal component *k.* ·     **Panel C:** Spectral tree of all 669 strains from commensal strain b...人类肠道微生物组包含同一物种的多种细菌菌株（即“菌株水平变异体”）。以具有生物学意义的方式描述菌株，而非单纯将其视为分类学对象，是一项重要的研究目标，但由于菌株水平变异的复杂性，该目标颇具挑战性。本研究对跨越细菌生命树的7000余株菌株的共演化模式进行了测定。以这些模式作为先验信息，对我们分离、测序并进行代谢谱分析的数百株肠道共生菌株展开研究，结果揭示了物种系统发育层级之下广泛存在的结构特征。通过共演化特征定义菌株，可仅基于菌株基因组内容预测其代谢表型并构建菌群联合体。本研究结果证明了菌株水平变异存在具有生物学相关性的组织形式，并为基于演化历史描述细菌菌株的新框架提供了依据。 材料与方法（更多细节与元数据见相关论文的补充材料） 构建人类肠道共生菌株库 粪便样本取自28名人类志愿者，年龄范围为18至63岁，中位年龄35岁。招募标准为过去1年内未使用过抗生素，且在知情同意时无糖尿病、结肠炎、自身免疫性疾病、癌症、肺炎、痢疾或蜂窝织炎病史。粪便样本采集方案经纪念斯隆凯特琳癌症中心（Memorial Sloan Kettering, MSK）与芝加哥大学批准。样本采集后立即置于厌氧舱中处理，经稀释后接种于多种培养基进行培养。琼脂培养基种类多样，包括以下类型：哥伦比亚血琼脂、脑心浸液+酵母提取物、脑心浸液+黏蛋白、脑心浸液+酵母提取物+乙酸盐或N-乙酰葡糖胺、强化梭菌琼脂、蛋白胨酵母葡萄糖培养基、酵母蛋白胨脂肪酸培养基（Yeast Casitone Fatt...）。 # 基于演化框架的人类肠道细菌描述（An evolution-based framework for describing human gut bacteria） 《基于演化框架的人类肠道细菌描述》补充数据 ## 数据与文件结构说明 **数据：XLSX文件** · **面板A：** 共生菌株库中669株菌株的同源基因簇（Orthologous Gene Groups, OGGs）注释数据矩阵。第一列为每株菌株的唯一标识符，后续列对应第一行所列的各同源基因簇数据。每个数值代表该菌株编码区中映射至该同源基因簇的序列数量（详见方法部分）。 · **面板B：** 669株菌株在描述UniProt数据库中共演化变异的主成分上的投影值（详见方法部分）。第一列为菌株ID，后续列对应7047个主成分，每个数值代表菌株i在主成分k上的贡献度。 · **面板C：** 来自共生菌株库的全部669株菌株的光谱树（原文截断）