Shotgun metagenomics methods enable characterization of microbial communities in human microbiome and environmental samples. Assembly of metagenome sequences does not output whole genomes, so computational binning methods have been developed to cluster sequences into genome 'bins'. These methods exploit sequence composition, species abundance, or chromosome organization but cannot fully distinguish closely related species and strains. We present a binning method that incorporates bacterial DNA methylation signatures, which are detected using single-molecule real-time sequencing. Our method takes advantage of these endogenous epigenetic barcodes to resolve individual reads and assembled contigs into species- and strain-level bins. We validate our method using synthetic and real microbiome sequences. In addition to genome binning, we show that our method links plasmids and other mobile genetic elements to their host species in a real microbiome sample. Incorporation of DNA methylation information into shotgun metagenomics analyses will complement existing methods to enable more accurate sequence binning.

中文翻译：

---

使用DNA甲基化，进行元基因组合并和质粒与细菌宿主基因组的关联。

弹枪宏基因组学方法可表征人类微生物组和环境样品中的微生物群落。元基因组序列的组装不能输出完整的基因组，因此已经开发了计算分箱方法以将序列聚类为基因组“箱”。这些方法利用序列组成，物种丰富度或染色体组织，但不能完全区分紧密相关的物种和菌株。我们提出了一种合并方法，该方法结合了细菌DNA甲基化标记，可使用单分子实时测序进行检测。我们的方法利用了这些内源性表观遗传条形码，可将单个阅读片段和重叠群解析为物种和品系级别的条带。我们使用合成的和真实的微生物组序列验证了我们的方法。除了基因组分箱外，我们表明，我们的方法将质粒和其他移动遗传元件链接到真实微生物组样品中的宿主物种。将DNA甲基化信息纳入shot弹枪宏基因组学分析将补充现有方法，以实现更准确的序列分箱。