Abstract
Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal tract are not well understood. This is partly due to a paucity of whole-virome datasets and limitations in current approaches for identifying viral sequences in metagenomics data. Here, combining a deep-learning based metagenomics binning algorithm with paired metagenome and metavirome datasets, we develop Phages from Metagenomics Binning (PHAMB), an approach that allows the binning of thousands of viral genomes directly from bulk metagenomics data, while simultaneously enabling clustering of viral genomes into accurate taxonomic viral populations. When applied on the Human Microbiome Project 2 (HMP2) dataset, PHAMB recovered 6,077 high-quality genomes from 1,024 viral populations, and identified viral-microbial host interactions. PHAMB can be advantageously applied to existing and future metagenomes to illuminate viral ecological dynamics with other microbiome constituents.
Highlights
Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal tract are not well understood
This ecosystem has been profoundly investigated for discoveries that can lead to diagnostics and treatments of gastrointestinal diseases such as inflammatory bowel disease (IBD) and colon cancer as well as type 2 diabetes (T2D)[1,2,3]
This has proven useful for the investigation of bacterial and archaeal microbiomes, but the approach has even more potential within viromics as viruses are much less conserved, more diverse, and harder to identify without universal genetic markers such as those found in bacterial organisms[32]
Summary
Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal tract are not well understood This is partly due to a paucity of whole-virome datasets and limitations in current approaches for identifying viral sequences in metagenomics data. We show an increase of up to 210% of HQ viral genomes extracted by combining contigs into viral bins Using this method to extract viruses from the microbial metagenomes of the HMP2 cohort we were able to delineate both viral and bacterial community structures. This allowed us to investigate viral population dynamics in tandem with predicted microbial hosts for instance identifying 123 and 230 viral populations infecting Faecalibacterium and Bacteroides genomes, respectively
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