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Mol Biol Evol. 2017 Nov 23. doi: 10.1093/molbev/msx304. [Epub ahead of print]

PHYLOSCANNER: Inferring Transmission from Within- and Between-Host Pathogen Genetic Diversity.

Author information

1
Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, UK.
2
Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, UK.
3
Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine and the NIHR Oxford BRC, University of Oxford, UK.
4
Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, UK.
5
Department of Veterinary Medicine, University of Cambridge, UK.
6
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.

Abstract

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. phyloscanner provides unprecedented resolution into the transmission process, allowing inference of the direction of transmission from sequence data alone. 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 contamination is flagged and removed. We illustrate phyloscanner on both viral and bacterial pathogens, namely HIV-1 sequenced on Illumina and Roche 454 platforms, HCV sequenced with the Oxford Nanopore MinION platform, and Streptococcus pneumoniae with sequences from multiple colonies per individual. phyloscanner is available from https://github.com/BDI-pathogens/phyloscanner.

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