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Mol Biol Evol. 2018 Mar 01;35(3):719-733. doi: 10.1093/molbev/msx304.

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

Molecular biology and evolution

Chris Wymant, Matthew Hall, Oliver Ratmann, David Bonsall, Tanya Golubchik, Mariateresa de Cesare, Astrid Gall, Marion Cornelissen, Christophe Fraser,

Affiliations

  1. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, United Kingdom.
  2. Department of Infectious Disease Epidemiology, Medical Research Council Centre for Outbreak Analysis and Modelling, Imperial College London, London, United Kingdom.
  3. Department of Mathematics, Imperial College London, London, United Kingdom.
  4. Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine and the NIHR Oxford BRC, University of Oxford, United Kingdom.
  5. Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, United Kingdom.
  6. Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
  7. 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.

PMID: 29186559 PMCID: PMC5850600 DOI: 10.1093/molbev/msx304

Abstract

A central feature of pathogen genomics is that different infectious particles (virions and bacterial cells) within an infected individual may be genetically distinct, with patterns of relatedness among 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 harbor 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.

© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Keywords: molecular epidemiology; multiple infection; pathogen diversity; pathogen genomics; pathogen transmission; phylogenetics

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