RT Journal Article SR Electronic T1 Phylogeographic and phylodynamic approaches to epidemiological hypothesis testing JF bioRxiv FD Cold Spring Harbor Laboratory SP 788059 DO 10.1101/788059 A1 Simon Dellicour A1 Sebastian Lequime A1 Bram Vrancken A1 Mandev S. Gill A1 Paul Bastide A1 Karthik Gangavarapu A1 Nate Matteson A1 Yi Tan A1 Louis du Plessis A1 Alexander A. Fisher A1 Martha I. Nelson A1 Marius Gilbert A1 Marc A. Suchard A1 Nathan D. Grubaugh A1 Kristian G. Andersen A1 Oliver G. Pybus A1 Philippe Lemey YR 2019 UL http://biorxiv.org/content/early/2019/10/01/788059.abstract AB Computational analyses of pathogen genomes are increasingly being used to unravel the dispersal history and transmission dynamics of epidemics. Here, we show how to go beyond historical reconstructions and use spatially-explicit phylogeographic and phylodynamic approaches to formally test epidemiological hypotheses. We focus on the spread and invasion of West Nile virus spread in North America that has been responsible for substantial impacts on public, veterinary and wildlife health. WNV isolates have been sampled at various times and locations across North America since its introduction to New York twenty years ago. We exploit this genetic data repository to demonstrate that factors hypothesised to affect viral dispersal and demography can be statistically tested. We find that WNV lineages tend to disperse faster in areas with higher temperatures and we identify temporal variation in temperature as a main predictor of viral genetic diversity through time. Finally, we compare inferred and simulated dispersal histories of lineages in order to assess the impact of migratory bird flyways on the rapid east-to-west continental spread of WNV. We find no evidence that viral lineages preferentially circulate within the same migratory flyway, suggesting a substantial role for non-migratory birds or mosquito dispersal along the longitudinal gradient. Our study demonstrates that the development and application of statistical approaches, coupled with comprehensive pathogen genomic data, can address epidemiological questions that might otherwise be difficult or unacceptably costly to answer.