PathFams: statistical detection of pathogen-associated protein domains

Background: A substantial fraction of genes identified within bacterial genomes encode proteins of unknown function. Identifying which of these proteins represent potential virulence factors, and mapping their key virulence determinants, is a challenging but important goal.

Results: To facilitate virulence factor discovery, we performed a comprehensive analysis of 17,929 protein domain families within the Pfam database, and scored them based on their overrepresentation in pathogenic versus non-pathogenic species, taxonomic distribution, relative abundance in metagenomic datasets, and other factors.

Conclusions: We identify pathogen-associated domain families, candidate virulence factors in the human gut, and eukaryotic-like mimicry domains with likely roles in virulence. Furthermore, we provide an interactive database called PathFams to allow users to explore pathogen-associated domains as well as identify pathogen-associated domains and domain architectures in user-uploaded sequences of interest. PathFams is freely available at https://pathfams.uwaterloo.ca .

Keywords: Environmental association; Hypothetical proteins; Lineage specificity; Pathogens; Proteins of unknown function; Virulence factors.