Model Misspecification Misleads Inference of the Spatial Dynamics of Disease Outbreaks

Epidemiology has been transformed by the advent of Bayesian phylodynamic models that allow researchers to infer the geographic history of pathogen dispersal over a set of discrete geographic areas (1, 2). These models provide powerful tools for understanding the spatial dynamics of disease outbreaks, but contain many parameters that are inferred from minimal geographic information ( i . e ., the single area in which each pathogen was sampled). Consequently, inferences under these models are inherently sensitive to our prior assumptions about the model parameters. Here, we demonstrate that the default priors used in empirical phylodynamic studies make strong and biologically unrealistic assumptions about the underlying geographic process. We provide empirical evidence that these unrealistic priors strongly (and adversely) impact commonly reported aspects of epidemiological studies, including: (1) the relative rates of dispersal between areas; (2) the importance of dispersal routes for the spread of pathogens among areas; (3) the number of dispersal events between areas, and; (4) the ancestral area in which a given outbreak originated. We offer strategies to avoid these problems, and develop tools to help researchers specify more biologically reasonable prior models that will realize the full potential of phylodynamic methods to elucidate pathogen biology and, ultimately, inform surveillance and monitoring policies to mitigate the impacts of disease outbreaks. Significance Statement Bayesian phylodynamic models have revolutionized epidemiology by enabling researchers to infer key aspects of the geographic history of disease outbreaks. These models contain many parameters that must be estimated from minimal information (the area from which each pathogen was sampled), rendering inferences under this approach inherently sensitive to the choice of priors on the model parameters. Here, we demonstrate that: (1) the priors assumed in ≈ 93% of surveyed phylodynamic studies make strong and biologically unrealistic assumptions, and; (2) these priors distort the conclusions of epidemiological studies. We offer strategies and tools to specify more reasonable priors that will enhance our ability to understand pathogen biology and, thereby, to mitigate disease.