Gene co-occurrence and its association with phage infectivity in bacterial pangenomes

Phages infect bacteria and have recently re-emerged as a promising strategy to combat bacterial infections. However, there is a lack of methods to predict whether and why a particular phage can or cannot infect a bacterial strain based on their genome sequences. Understanding the complex interactions between phages and their bacterial hosts is thus of considerable interest. We recently developed Goldfinder, a phylogenetic method to discover gene co-occurrences across bacterial pangenomes. Here, we expand Goldfinder to infer which gene presences or absences influence bacterial sensitivity to phages. By integrating a bacterial pangenome with an experimentally determined host range matrix, we infer associations between phage infectivity and the presence of accessory genes in bacterial pangenomes. The presented approach can be applied to predict bacterial genes that potentially enable phage infection, bacterial genes that prevent phage infection, and potential interactions between particular bacterial and phage accessory genes. Finally, the predicted interactions are clustered and visualized with the software Cytoscape. Here, we present a method to identify candidate genes within the pool of mobile accessory genes that may contribute to phage-host interactions. This approach will help to set up follow-up experiments and to understand the complex interactions between phages and bacteria.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.