Department of Ecology and Evolutionary Biology, Princeton University, New Jersey, USA.
Fogarty International Center, National Institute of Health, Bethesda, MD, USA.
PLoS Comput Biol. 2019 Apr 5;15(4):e1006955. doi: 10.1371/journal.pcbi.1006955. eCollection 2019 Apr.
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.
系统发育动力学建模,即研究流行病学和进化过程的联合动力学,近年来由于基因组数据的日益丰富和统计建模的进步取得了重大进展。这些进展极大地提高了我们对许多重要病原体传播动力学的理解。然而,仍然缺乏有效的、有针对性的诊断工具来系统地检测模型的不适当指定。开发此类工具对于模型批评、改进和校准至关重要。利用潜在残差进行模型评估的想法已经在一般的时空流行病学环境中得到了利用。具体来说,通过对给定的流行病学过程提出适当设计的非中心化、重新参数化,可以构建具有已知抽样分布的潜在残差,可用于量化模型不适当指定的证据。在本文中,我们将这个想法扩展到为系统发育动力学模型制定一个新的模型诊断框架。使用模拟示例,我们表明我们的框架可以有效地检测系统发育动力学模型中的特定形式的不适当指定,特别是在超级传播的情况下。我们还通过将该框架应用于描述英国局部口蹄疫(FMD)爆发的数据集,得出了强有力的证据,证明爆发中不存在宿主内多样性的假设是错误的。我们进一步证明,我们的框架可以通过提出一种宿主内多样性模型来促进现实场景中的模型校准,该模型似乎比假设 FMD 病毒宿主内没有多样性的模型更能拟合数据。