Abstract
ABSTRACTBacteriophages are the most abundant and diverse biological entities on the planet, and new phage genomes are being discovered at a rapid pace. As more phage genomes are published, new methods are needed for placing these genomes in an ecological and evolutionary context. Phages are difficult to study by phylogenetic methods, because they exchange genes regularly, and no single gene is conserved across all phages. Here, we demonstrate how gene-level networks can provide a high-resolution view of phage genetic diversity and offer a novel perspective on virus ecology. We focus our analyses on virus host range and show how network topology corresponds to host relatedness, how to find groups of genes with the strongest host-specific signatures, and how this perspective can complement phage host prediction tools. We discuss extensions of gene network analysis to predicting the emergence of phages on new hosts, as well as applications to features of phage biology beyond host range.
Highlights
Bacteriophages are the most abundant and diverse biological entities on the planet, and new phage genomes are being discovered at a rapid pace
There exist subsets of nodes that form subgraphs in which members have more connections in common with each other than with the rest of the network. We formally identified these subsets of interconnected nodes using the Markov Cluster algorithm (MCL) [27]
We developed an evolutionary algorithm, mimax, to identify the subset of genes that maximizes the mutual information of MCL clusters in the gene network and host associations
Summary
Bacteriophages are the most abundant and diverse biological entities on the planet, and new phage genomes are being discovered at a rapid pace. We find that the network reflects the relatedness among phage hosts, and phages with genes that are closer in the network are likelier to infect similar hosts This approach can be used to identify genes that affect host range, and we discuss possible extensions to analyze other aspects of viral ecology. Genome-level network analyses are useful, because they make it possible to visualize distant phage relationships in place of phylogenies [12, 16]. These approaches have shown how modules of genes underlying the genome network may relate to different phage lifestyles and potentially host range [16, 18].
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