PHYLOSCANNER: Analysing Within- and Between-Host Pathogen Genetic Diversity to Identify Transmission, Multiple Infection, Recombination and Contamination. Phyloscanner

Pathogen genomics is proving to be a revolutionary tool in epidemiology, medicine and biology. A central feature of pathogen genomics is that different infectious particles (virions, bacterial cells, etc.) within an infected individual may be genetically distinct, with patterns of relatedness amongst infectious particles being the result of both within-host evolution and transmission from one host to the next. Here we present a new software tool, phyloscanner, which analyses pathogen diversity from multiple infected hosts, and so provides unprecedented resolution into the transmission process. Multiply infected individuals are also identified, as they harbour subpopulations of infectious particles that are not connected by within-host evolution, except where recombinant types emerge. Low-level laboratory contamination is flagged and removed. We illustrate phyloscanner on both viral and bacterial pathogens, including HIV-1 sequenced on Illumina and Roche 454 platforms, HCV on Oxford Nanopore, and Streptococcus pneumoniae with multiple colonies per individual.