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

• Published in: Nature communications Vol. 13; no. 1; p. 3175
• Main Authors: Chen, Liang, Zhao, Na, Cao, Jiabao, Liu, Xiaolin, Xu, Jiayue, Ma, Yue, Yu, Ying, Zhang, Xuan, Zhang, Wenhui, Guan, Xiangyu, Yu, Xiaotong, Liu, Zhipeng, Fan, Yanqun, Wang, Yang, Liang, Fan, Wang, Depeng, Zhao, Linhua, Song, Moshi, Wang, Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.06.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 631/114/2164; 631/208/325/1506; CRISPR; Depth profiling; Gastrointestinal Microbiome - genetics; Genetic diversity; Genomes; High-Throughput Nucleotide Sequencing; Humanities and Social Sciences; Intestinal microflora; Inversions; Laboratories; Metabolism; Metabolites; Metabolome - genetics; Metagenome; Metagenomics; Microbiomes; multidisciplinary; Nanopores; Phenotypes; Science; Science (multidisciplinary); Stem cells
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30857-9

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. Here, Wang and colleagues combine short and long sequencing reads to characterize structural variations, prophage and CRISPR spacer elements in human gut microbiomes, and reveal functional differences at a finer level of bacterial strains.