Learning RNA Viral Disease Dynamics from Molecular Sequence Data
While myriad studies exist which reconstruct patterns of discrete trait evolution along an inferred phylogeny, attempts to translate the results of phyloegographic analyses into actionable metrics that can be used by public health agencies to direct the development of interventions aimed at reducing pathogen spread are conspicuously absent from the literature. In this dissertation, I focus on developing an intuitive metric, the phylogenetic risk ratio (PRR), which I use to translate the results of Bayesian phylogeographic modeling studies into a form actionable by public health agencies. I apply the PRR to two case studies: i) age-associated diffusion of influenza A/H3N2 during the 2016-17 US epidemic and ii) host associated diffusion of West Nile virus in the US. I discuss the limitations of this (and Bayesian phylogeographic) approaches when studying non-geographic traits for which limited metadata is available in public molecular sequence databases and statistically principled solutions to the missing metadata problem in the phylogenetic context. Then, I perform a simulation study to evaluate the statistical performance of the missing metadata solution. Finally, I provide a solution for researchers whom are interested in using the PRR and phylogenetic UTMs in their own genomic epidemiological studies yet are deterred by the idiosyncratic, error-prone processes required to implement these methods using popular Bayesian phylogenetic inference software packages. My solution, Build-A-BEAST, is a publicly available, object-oriented system written in python which aims to reduce the complexity and idiosyncrasy of creating XML files necessary to perform the aforementioned analyses. This dissertation extends the conceptual framework of Bayesian phylogeographic methods, develops a method to translates the output of phylogenetic models into an actionable form, evaluates the use of priors for missing metadata, and, finally, provides a solution which eases the implementation of these methods. In doing so, I lay the foundation for future work in disseminating and implementing Bayesian phylogeographic methods for routine public health surveillance.
- Author (aut): Vaiente, Matteo
- Thesis advisor (ths): Scotch, Matthew
- Committee member: Mubayi, Anuj
- Committee member: Liu, Li
- Publisher (pbl): Arizona State University