Model diagnostics and refinement for phylodynamic models

Phylodynamic modelling, which studies the joint dynamics of epidemiological and evolutionary processes, has made significant progress in recent years due to increasingly available genomic data and advances in statistical modelling. These advances have greatly improved our understanding of transmission dynamics of many important pathogens. Nevertheless, there remains a lack of effective, targetted diagnostic tools for systematically detecting model mis-specification. Development of such tools is essential for model criticism, refinement, and calibration. The idea of utilising latent residuals for model assessment has already been exploited in general spatio-temporal epidemiological settings. Specifically, by proposing appropriately designed non-centered, re-parameterizations of a given epidemiological process, one can construct latent residuals with known sampling distributions which can be used to quantify evidence of model mis-specification. In this paper, we extend this idea to formulate a novel model-diagnostic framework for phylodynamic models. Using simulated examples, we show that our framework may effectively detect a particular form of mis-specification in a phylodynamic model, particularly in the event of superspreading. We also exemplify our approach by applying the framework to a dataset describing a local foot-and-mouth (FMD) outbreak in the UK, eliciting strong evidence against the assumption of no within-host-diversity in the outbreak. We further demonstrate that our framework can facilitate model calibration in real-life scenarios, by proposing a within-host-diversity model which appears to offer a better fit to data than one that assumes no within-host-diversity of FMD virus.Author summary: Integrated modelling of conventional epidemiological data and modern genomic data (i.e. phylodynamics) has made significant progress in recent years, due to the ever-increasing availability of genomic data and development of statistical methods. However, there is a lack of tools for carrying out effective diagnostics for phylodynamic models. We propose a novel model diagnostic framework that involves a latent residual process which is a priori independent of model assumptions and which can be used to quantify, and reveal the nature of, model inadequacy. Our results suggest that our framework may systematically detect deviation from a particular model assumption and greatly facilitate subsequent model calibration.