Emerging viruses have the potential to impose substantial mortality, morbidity and economic burdens on human populations. Tracking the spread of infectious diseases to assist in their control has traditionally relied on the analysis of case data gathered as the outbreak proceeds. Here, we describe how many of the key questions in infectious disease epidemiology, from the initial detection and characterization of outbreak viruses, to transmission chain tracking and outbreak mapping, can now be much more accurately addressed using recent advances in virus sequencing and phylogenetics. We highlight the utility of this approach with the hypothetical outbreak of an unknown pathogen, ‘Disease X’, suggested by the World Health Organization to be a potential cause of a future major epidemic. We also outline the requirements and challenges, including the need for flexible platforms that generate sequence data in real-time, and for these data to be shared as widely and openly as possible.

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We thank G. Dudas and S. Knemeyer for help with figure creation. N.D.G. is supported by NIH training grant 5T32AI007244-33. P.L. and A.R. acknowledge funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725422-ReservoirDOCS) and from the Wellcome Trust Collaborative Award (grant number 206298/Z/17/Z—ARTICnetwork). P.L. acknowledges support by the Research Foundation—Flanders (‘Fonds voor Wetenschappelijk Onderzoek - Vlaanderen’, G066215N, G0D5117N and G0B9317N). O.G.P. is supported by the European Union’s Seventh Framework Programme (FP7/2007-2013)/European Research Council (614725-PATHPHYLODYN) and by the Oxford Martin School. E.C.H. is supported by an ARC Australian Laureate Fellowship (FL170100022). K.G.A. is a Pew Biomedical Scholar, and is supported by NIH NCATS CTSA UL1TR002550, NIAID contract HHSN272201400048C, NIAID R21AI137690, NIAID U19AI135995, and The Ray Thomas Foundation.

Author information


  1. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA

    • Nathan D. Grubaugh
    •  & Kristian G. Andersen
  2. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA

    • Nathan D. Grubaugh
  3. Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA

    • Jason T. Ladner
  4. Department of Microbiology and Immunology, Rega Institute, KU Leuven - University of Leuven, Leuven, Belgium

    • Philippe Lemey
  5. Department of Zoology, University of Oxford, Oxford, UK

    • Oliver G. Pybus
  6. Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK

    • Andrew Rambaut
  7. Fogarty International Center, National Institutes of Health, Bethesda, MD, USA

    • Andrew Rambaut
  8. Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia

    • Edward C. Holmes
  9. Scripps Research Translational Institute, La Jolla, CA, USA

    • Kristian G. Andersen


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All listed authors have contributed to the conceptualization, writing and preparation of the manuscript.

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The authors declare no competing interests.

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Correspondence to Jason T. Ladner or Andrew Rambaut or Edward C. Holmes.

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