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Genome-centric analysis of short and long read metagenomes reveals uncharacterized microbiome diversity in Southeast Asians

Jean-Sebastien Gounot, Minghao Chia, Denis Bertrand, Woei-Yuh Saw, Aarthi Ravikrishnan, Adrian Low, Yichen Ding, Amanda Hui Qi Ng, Linda Wei Lin Tan, Yik-Ying Teo (), Henning Seedorf () and Niranjan Nagarajan ()
Additional contact information
Jean-Sebastien Gounot: Genome Institute of Singapore
Minghao Chia: Genome Institute of Singapore
Denis Bertrand: Genome Institute of Singapore
Woei-Yuh Saw: National University of Singapore
Aarthi Ravikrishnan: Genome Institute of Singapore
Adrian Low: Temasek Life Sciences Laboratory, 1 Research Link
Yichen Ding: Temasek Life Sciences Laboratory, 1 Research Link
Amanda Hui Qi Ng: Genome Institute of Singapore
Linda Wei Lin Tan: National University of Singapore
Yik-Ying Teo: National University of Singapore
Henning Seedorf: Temasek Life Sciences Laboratory, 1 Research Link
Niranjan Nagarajan: Genome Institute of Singapore

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Despite extensive efforts to address it, the vastness of uncharacterized ‘dark matter’ microbial genetic diversity can impact short-read sequencing based metagenomic studies. Population-specific biases in genomic reference databases can further compound this problem. Leveraging advances in hybrid assembly (using short and long reads) and Hi-C technologies in a cross-sectional survey, we deeply characterized 109 gut microbiomes from three ethnicities in Singapore to comprehensively reconstruct 4497 medium and high-quality metagenome assembled genomes, 1708 of which were missing in short-read only analysis and with >28× N50 improvement. Species-level clustering identified 70 (>10% of total) novel gut species out of 685, improved reference genomes for 363 species (53% of total), and discovered 3413 strains unique to these populations. Among the top 10 most abundant gut bacteria in our study, one of the species and >80% of strains were unrepresented in existing databases. Annotation of biosynthetic gene clusters (BGCs) uncovered more than 27,000 BGCs with a large fraction (36–88%) unrepresented in current databases, and with several unique clusters predicted to produce bacteriocins that could significantly alter microbiome community structure. These results reveal significant uncharacterized gut microbial diversity in Southeast Asian populations and highlight the utility of hybrid metagenomic references for bioprospecting and disease-focused studies.

Date: 2022
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DOI: 10.1038/s41467-022-33782-z

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