Distributed under Creative Commons Cc-by 4.0 Strain-and Plasmid-level Deconvolution of a Synthetic Metagenome by Sequencing Proximity Ligation Products
Distributed under Creative Commons Cc-by 4.0 Strain-and Plasmid-level Deconvolution of a Synthetic Metagenome by Sequencing Proximity Ligation Products
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根据 Creative Commons Cc-by 4.0 通过邻近连接产物测序对合成宏基因组进行菌株和质粒水平解卷积
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通讯作者：
J. Eisen
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作者：
C. Beitel;A. Darling;L. Froenicke;Jenna M Lang;I. Korf;R. Michelmore;J. Eisen
宏基因组学是研究微生物群落的一种有价值的工具，但由于难以将结果序列“归类”到与构成群落的单个物种和菌株相对应的组中，因此受到限制。此外，目前还没有方法来跟踪移动DNA元件（如质粒）在群落中的流动，或确定其中哪些是在同一细胞内共定位的。我们通过应用Hi-C（一种最初设计用于真核生物三维基因组结构研究的技术）来测量DNA序列的细胞共定位来解决这些限制。我们利用从简单合成宏基因组样本生成的Hi-C数据，准确地将宏基因组组装组划分为包含每个物种几乎完整基因组的组。Hi-C数据还可靠地将质粒与其宿主的染色体以及彼此之间联系起来。我们进一步证明，Hi-C数据提供了菌株特异性基因型的远程信号，表明这些数据可能对微生物种群的高分辨率基因分型有用。我们的工作表明，Hi-C测序数据为宏基因组分析提供了有价值的信息，这是目前其他方法无法获得的。这种宏基因组Hi-C方法可以促进未来微生物精细群体结构的研究，以及抗生素抗性质粒（或其他遗传元件）如何在微生物群落中动员的研究。该方法不限于微生物学；其他异质细胞群体的遗传结构也可以用这种技术进行研究。Beitel et al.(2014)，菌株和质粒水平的合成宏基因组的反卷积测序邻近连接产物。PeerJ 2: e415;DOI 10.7717 / peerj.415
Metagenomics is a valuable tool for the study of microbial communities but has been limited by the difficulty of " binning " the resulting sequences into groups corresponding to the individual species and strains that constitute the community. Moreover, there are presently no methods to track the flow of mobile DNA elements such as plasmids through communities or to determine which of these are co-localized within the same cell. We address these limitations by applying Hi-C, a technology originally designed for the study of three-dimensional genome structure in eukary-otes, to measure the cellular co-localization of DNA sequences. We leveraged Hi-C data generated from a simple synthetic metagenome sample to accurately cluster metagenome assembly contigs into groups that contain nearly complete genomes of each species. The Hi-C data also reliably associated plasmids with the chromosomes of their host and with each other. We further demonstrated that Hi-C data provides a long-range signal of strain-specific genotypes, indicating such data may be useful for high-resolution genotyping of microbial populations. Our work demonstrates that Hi-C sequencing data provide valuable information for metagenome analyses that are not currently obtainable by other methods. This metagenomic Hi-C method could facilitate future studies of the fine-scale population structure of microbes, as well as studies of how antibiotic resistance plasmids (or other genetic elements) mobilize in microbial communities. The method is not limited to microbiology; the genetic architecture of other heterogeneous populations of cells could also be studied with this technique. How to cite this article Beitel et al. (2014), Strain-and plasmid-level deconvolution of a synthetic metagenome by sequencing proximity ligation products. PeerJ 2:e415; DOI 10.7717/peerj.415
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11.3
作者：
Blainey PC
通讯作者：
Blainey PC