IMPORTANCE: Bacteriophage genomes are pervasively mosaic, presenting challenges to describing phage relatedness. Here, we describe PhamClust, a bioinformatic approach for phage genome comparisons that uses a new metric of proteomic equivalence quotient for comparative genomics. PhamClust reliably assorts genomes into groups or clusters of related phages and can subdivide clusters into subclusters. PhamClust is computationally efficient and can readily process thousands of phage genomes. It is also a useful analytic tool for exploring the different types of inter-genome relatedness characteristic of phages in different clusters.
