Journal article

Influenza virus drug resistance: A time-sampled population genetics perspective

  • Foll, Matthieu School of Life Sciences, EPF), Lausanne, Switzerland - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
  • Poh, Yu-Ping Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland - Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Renzette, Nicholas Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Ferrer-Admetlla, Anna School of Life Sciences, EPF), Lausanne, Switzerland - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland - Department of Biology, Biochemistry Unit, University of Fribourg, Switzerland
  • Bank, Claudia School of Life Sciences, EPF), Lausanne, Switzerland - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
  • Shim, Hyunjin School of Life Sciences, EPF), Lausanne, Switzerland - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
  • Malaspinas, Anna-Sapfo Center for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark
  • Ewing, Gregory School of Life Sciences, EPF), Lausanne, Switzerland - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
  • Liu, Ping Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Wegmann, Daniel Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland - Department of Biology, Biochemistry Unit, University of Fribourg, Switzerland
  • Caffrey, Daniel R. Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Zeldovich, Konstantin B. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Bolon, Daniel N. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Wang, Jennifer P. Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Kowalik, Timothy F. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Schiffer, Celia A. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Finberg, Robert W. Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Jensen, Jeffrey D. School of Life Sciences, EPF), Lausanne, Switzerland - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
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    27.02.2014
Published in:
  • PLoS Genet. - 2014, vol. 10, no. 2, p. e1004185
English The challenge of distinguishing genetic drift from selection remains a central focus of population genetics. Time-sampled data may provide a powerful tool for distinguishing these processes, and we here propose approximate Bayesian, maximum likelihood, and analytical methods for the inference of demography and selection from time course data. Utilizing these novel statistical and computational tools, we evaluate whole-genome datasets of an influenza A H1N1 strain in the presence and absence of oseltamivir (an inhibitor of neuraminidase) collected at thirteen time points. Results reveal a striking consistency amongst the three estimation procedures developed, showing strongly increased selection pressure in the presence of drug treatment. Importantly, these approaches re-identify the known oseltamivir resistance site, successfully validating the approaches used. Enticingly, a number of previously unknown variants have also been identified as being positively selected. Results are interpreted in the light of Fisher's Geometric Model, allowing for a quantification of the increased distance to optimum exerted by the presence of drug, and theoretical predictions regarding the distribution of beneficial fitness effects of contending mutations are empirically tested. Further, given the fit to expectations of the Geometric Model, results suggest the ability to predict certain aspects of viral evolution in response to changing host environments and novel selective pressures.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/303440
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