Fast and accurate metagenotyping of the human gut microbiome with GT-Pro

Shi, Zhou Jason; Dimitrov, Boris; Zhao, Chunyu; Nayfach, Stephen; Pollard, Katherine S.

doi:10.1038/s41587-021-01102-3

Title: Fast and accurate metagenotyping of the human gut microbiome with GT-Pro

Journal Article · 22 December 2021 · Nature Biotechnology

DOI: https://doi.org/10.1038/s41587-021-01102-3 · OSTI ID:1894075

Shi, Zhou Jason ^[1]; Dimitrov, Boris ^[2]; Zhao, Chunyu ^[3];

^[4];

^[5]

Chan Zuckerberg Biohub, San Francisco, CA (United States); Gladstone Institutes, San Francisco, CA (United States)
Chan Zuckerberg Initiative, Redwood City, CA (United States)
Chan Zuckerberg Biohub, San Francisco, CA (United States)
USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Chan Zuckerberg Biohub, San Francisco, CA (United States); Gladstone Institutes, San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States)

Single nucleotide polymorphisms (SNPs) in metagenomics are used to quantify population structure, track strains and identify genetic determinants of microbial phenotypes. However, existing alignment-based approaches for metagenomic SNP detection require high-performance computing and enough read coverage to distinguish SNPs from sequencing errors. To address these issues, we developed the GenoTyper for Prokaryotes (GT-Pro), a suite of methods to catalog SNPs from genomes and use unique k-mers to rapidly genotype these SNPs from metagenomes. Compared to methods that use read alignment, GT-Pro is more accurate and two orders of magnitude faster. Here, using high-quality genomes, we constructed a catalog of 104 million SNPs in 909 human gut species and used unique k-mers targeting this catalog to characterize the global population structure of gut microbes from 7,459 samples. GT-Pro enables fast and memory-efficient metagenotyping of millions of SNPs on a personal computer.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Science Fund (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1894075

Journal Information:: Nature Biotechnology, Journal Name: Nature Biotechnology Journal Issue: 4 Vol. 40; ISSN 1087-0156

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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