Abstract
Genetic sequence data on pathogens have great potential to inform inference of their transmission dynamics ultimately leading to better disease control. Where genetic change and disease transmission occur on comparable timescales additional information can be inferred via the joint analysis of such genetic sequence data and epidemiological observations based on clinical symptoms and diagnostic tests. Although recently introduced approaches represent substantial progress, for computational reasons they approximate genuine joint inference of disease dynamics and genetic change in the pathogen population, capturing partially the joint epidemiological-evolutionary dynamics. Improved methods are needed to fully integrate such genetic data with epidemiological observations, for achieving a more robust inference of the transmission tree and other key epidemiological parameters such as latent periods. Here, building on current literature, a novel Bayesian framework is proposed that infers simultaneously and explicitly the transmission tree and unobserved transmitted pathogen sequences. Our framework facilitates the use of realistic likelihood functions and enables systematic and genuine joint inference of the epidemiological-evolutionary process from partially observed outbreaks. Using simulated data it is shown that this approach is able to infer accurately joint epidemiological-evolutionary dynamics, even when pathogen sequences and epidemiological data are incomplete, and when sequences are available for only a fraction of exposures. These results also characterise and quantify the value of incomplete and partial sequence data, which has important implications for sampling design, and demonstrate the abilities of the introduced method to identify multiple clusters within an outbreak. The framework is used to analyse an outbreak of foot-and-mouth disease in the UK, enhancing current understanding of its transmission dynamics and evolutionary process.
Highlights
Epidemiological data for infectious disease, defined here as clinical observation, diagnostic test results and associated covariates such as location, only indirectly reflect underlying contact structures, exposure times, and other aspects of disease dynamics
When genetic change and disease transmission occur on comparable time scales joint analysis of epidemiological and genetic data can lead to valuable insights concerning epidemic outbreaks
We perform inference of transmission dynamics based on epidemics simulated under conditions that reflect real-world scenarios, with the primary aim of assessing the performance of our inference framework in a range of circumstances
Summary
In the midst of increasingly available sequence data of pathogens, a key challenge is to better integrate these data with traditional epidemiological data, with the proximate goal of reliable prediction and the ultimate aim of effective management of disease outbreaks. Substantial advances have been made for such an integration, and they have improved our understandings of many disease dynamics which are not available otherwise, current methods have relied on fast algorithms, rather than achieving a systematic integration and accurate inference of the joint epidemiological-evolutionary process. Building on methods in current literature, this paper describes a novel Bayesian approach for systematically integrating these two streams of data. We propose a computationally tractable Bayesian inferential algorithm which takes the full joint epidemiological-evolutionary process into account. Using this algorithm, we study systematically the value of genetic data, providing valuable insights into future sampling designs. The algorithm is subsequently applied to real-world dataset describing the spread of animal foot-andmouth disease in the UK, demonstrating the importance of such a systematic integration achieved with our methodology
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