Short- and long-read metagenomics expand individualized structural variations in gut microbiomes

Liang Chen, Na Zhao, Jiabao Cao, Xiaolin Liu, Jiayue Xu, Yue Ma, Ying Yu, Xuan Zhang, Wenhui Zhang, Xiangyu Guan, Xiaotong Yu, Zhipeng Liu, Yanqun Fan, Yang Wang, Fan Liang, Depeng Wang, Linhua Zhao, Moshi Song () and Jun Wang ()
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Liang Chen: Chinese Academy of Sciences
Na Zhao: Chinese Academy of Sciences
Jiabao Cao: Chinese Academy of Sciences
Xiaolin Liu: Chinese Academy of Sciences
Jiayue Xu: Chinese Academy of Sciences
Yue Ma: Chinese Academy of Sciences
Ying Yu: Chinese Academy of Sciences
Xuan Zhang: Chinese Academy of Sciences
Wenhui Zhang: Chinese Academy of Sciences
Xiangyu Guan: Chinese Academy of Sciences
Xiaotong Yu: China Academy of Chinese Medical Sciences
Zhipeng Liu: Biotree-Shanghai
Yanqun Fan: Biotree-Shanghai
Yang Wang: GrandOmics Biosciences
Fan Liang: GrandOmics Biosciences
Depeng Wang: GrandOmics Biosciences
Linhua Zhao: China Academy of Chinese Medical Sciences
Moshi Song: University of Chinese Academy of Sciences
Jun Wang: Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract In-depth profiling of genetic variations in the gut microbiome is highly desired for understanding its functionality and impacts on host health and disease. Here, by harnessing the long read advantage provided by Oxford Nanopore Technology (ONT), we characterize fine-scale genetic variations of structural variations (SVs) in hundreds of gut microbiomes from healthy humans. ONT long reads dramatically improve the quality of metagenomic assemblies, enable reliable detection of a large, expanded set of structural variation types (notably including large insertions and inversions). We find SVs are highly distinct between individuals and stable within an individual, representing gut microbiome fingerprints that shape strain-level differentiations in function within species, complicating the associations to metabolites and host phenotypes such as blood glucose. In summary, our study strongly emphasizes that incorporating ONT reads into metagenomic analyses expands the detection scope of genetic variations, enables profiling strain-level variations in gut microbiome, and their intricate correlations with metabolome.

Date: 2022
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DOI: 10.1038/s41467-022-30857-9

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