Computational Methods for Assessment and Prediction of Viral Evolutionary and Epidemiological Dynamics

The ability to comprehend the dynamics of viruses’ transmission and their evolution, even to a limited extent, can significantly enhance our capacity to predict and control the spread of infectious diseases. An example of such significance is COVID-19 caused by the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). In this dissertation, I am proposing computational models that present more precise and comprehensive approaches in viral outbreak investigations and epidemiology, providing invaluable insights into the transmission dynamics, and potential inter- ventions of infectious diseases by facilitating the timely detection of viral variants. The first model is a mathematical framework based on population dynamics for the calculation of a numerical measure of the fitness of SARS-CoV-2 subtypes. The second model I propose here is a transmissibility estimation method based on a Bayesian approach to calculate the most likely fitness landscape for SARS-CoV-2 using a generalized logistic sub-epidemic model. Using the proposed model I estimate the epistatic interaction networks of spike protein in SARS-CoV-2. Based on the community structure of these epistatic networks, I propose a computational framework that predicts emerging haplotypes of SARS-CoV-2 with altered transmissibility. The last method proposed in this dissertation is a maximum likelihood framework that integrates phylogenetic and random graph models to accurately infer transmission networks without requiring case-specific data

Bayesian methods for source attribution using HIV deep sequence data

The advent of pathogen deep-sequencing technology provides new opportunities for infec- tious disease surveillance, especially for fast-evolving viruses like human immunodeficiency virus (HIV). In particular, multiple reads per host contain detailed information on viral within- host diversity. This information allows the reconstruction of partial directed transmission networks, where estimates of who is source and who is recipient are directly available from the phylogenetic ordering of the viruses of any two individuals. This is a new approach for phylodynamics, and the topic of my thesis. In this thesis, I present updates to the bioinformatics pipeline used by the Phylogenetics And Networks for Generalised Epidemics in Africa consortium for processing HIV deep sequence data and running the phyloscanner program. I then present a semi-parametric Bayesian Poisson model for inferring infectious disease transmission flows and the sources of infection at the population level. The framework is computationally scalable in high- dimensional flow spaces thanks to Hilbert Space Gaussian process approximations, allows for sampling bias adjustments, and estimation of gender- and age-specific transmission flows at a finer resolution than previously possible. In this sense, the methods that I developed enable us to overcome some problems which have been unable to be solved by conventional phylodynamic approaches. We apply the approach to densely sampled, population-based HIV deep-sequence data from Rakai, Uganda. I focus on characterising age-specific transmission dynamics, and examining the sources of HIV infections in adolescent and young women in particular.Open Acces

Recent CMV Research

I am very pleased with this Viruses Special Issue. Of particular interest to families and caregivers affected by CMV diseases are several papers: addressing prevention of CMV infection of trophoblast cells (Zydek et al., 2014), CMV latency (Sinclair and Reeves, 2013), as well as of CMV lung infections in non-HIV infected children (Restrepo-Gualteros et al., 2014). Our ability to enhance immune responses for controlling CMV infection (Hanley and Bollard, 2014) and new strategies for CMV vaccine development guided by non-human primate studies (Deere and Barry, 2014) are discussed in two excellent reviews. Several articles address the CMV manipulation of the immune system, both innate and adaptive immune responses (Stevenson et al., 2014, Fink et al, 2013, 2014, Raghavan et al., 2014) and of DNA damage responses (E and Kowalik, 2014; Kulkarni and Fortunato, 2014). [...