Massive expansion of human gut bacteriophage diversity

Abstract

Summary Bacteriophages drive evolutionary change in bacterial communities by creating gene flow networks that fuel ecological adaptions. However, the extent of viral diversity and its prevalence in the human gut remains largely unknown. Here, we introduce the Gut Phage Database, a collection of ∼142,000 non-redundant viral genomes (>10 kb) obtained by mining a dataset of 28,060 globally distributed human gut metagenomes and 2,898 reference genomes of cultured gut bacteria. Host assignment revealed that viral diversity is highest in the Firmicutes phyla and that ∼36% of viral clusters (VCs) are not restricted to a single species, creating gene flow networks across phylogenetically distinct bacterial species. Epidemiological analysis uncovered 280 globally distributed VCs found in at least 5 continents and a highly prevalent phage clade with features reminiscent of p-crAssphage. This high-quality, large-scale catalog of phage genomes will improve future virome studies and enable ecological and evolutionary analysis of human gut bacteriophages.

BACPHLIP: predicting bacteriophage lifestyle from conserved protein domains

“…Critically, BACPHLIP rapidly creates predictions from un-annotated genome sequences alone, and thus can facilitate large-scale studies into phage genome evolution ( Moura de Sousa et al, 2021 ). Given the rapid expansion of phage genome data sets ( Roux et al, 2021 ; Camarillo-Guerrero et al, 2021 ), comparative genomic analyses have the potential to drastically increase our understanding of phage diversity and function.…”

“…Phage lifestyle should ultimately be determined experimentally, but such labor-intensive approaches are impractical for the entirety of newly discovered phage genomes ( Camarillo-Guerrero et al, 2021 ). Using computational methods, McNair, Bailey & Edwards (2012) developed a Random Forest classifier (PHACTS) to predict lifestyle based off of sequence similarity to a set of query proteins (randomly selected from the phage proteome training set).…”

Gut Phage Database: phage mining in the cave of wonders

“…The diversity of the viruses in the human gut remains mostly unexplored. To shed some light on this known unknown, Camarillo-Guerrero et al 1 developed the Gut Phage Database (GPD), which includes 142,809 non-redundant gut phages obtained from analyzing 28,060 shotgun metagenome datasets.…”

“… 2 Bacteria and their viruses, called phages, are the most abundant microbes in the human gut in an approximate ratio of 1:1 and a total abundance of about 10e13. 1 – 3 Yet, we currently have little more than anecdotal data about gut phages relative to what we know about their bacterial hosts. 2 The gut bacteria play central roles in human metabolism, immune modulation, and protection against pathogens.…”

Generating complex patterns of gene expression without regulatory circuits

“…An extraordinary number of phages have been discovered in recent years, but only a small number of these have been interrogated experimentally [58][59][60][61][62]. Computational approaches can help to better characterize the general constraints and principles that affect genome organization and function, and can additionally provide a way to engineer phages based on predetermined design constraints.…”