Abstract
Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota.
Highlights
Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses
We picked more than 10,000 bacterial isolates that were taxonomically classified using 16 S ribosomal RNA (rRNA) gene sequencing
To evaluate how the Human Gastrointestinal Bacteria Culture Collection (HBC) genome collection alone and the complete Human Gastrointestinal Bacteria Genome Collection (HGG) collection compares to the existing Human Microbiome Project (HMP) genomes, we considered which of the metagenome-assembled genome sequences (MAGs) could be identified using each collection as a reference database
Summary
Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. Genomes derived from de novo metagenomic assemblies may be incomplete or may represent chimeric species populations, unlike highquality reference genomes generated from pure cultures[12] These factors limit the accuracy of high-resolution taxonomic classification and functional analysis using metagenome-derived genomes. Comprehensive collections of reference-quality bacterial genomes enable accurate, reference-based metagenomic analysis (RBMA) and achieve species-, subspecies- and strain-level taxonomic classification of the bacterial composition of a microbiome. With recent advances in bacterial culturing methods, it is possible to grow and purify most bacteria from the human GI tract in the laboratory[17,18,19,20]
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