Fellay, JacquesXu, Zhi Ming2023-07-172023-07-17202310.5075/epfl-thesis-10351https://infoscience.epfl.ch/handle/20.500.14299/199268Hosts and pathogens are involved in a long-standing evolutionary arms race characterized by successive rounds of evolution. Specifically, while hosts evolve resistance against infections, pathogens adapt to re-establish virulence. Since the signatures of this evolutionary process are imprinted on both genomes, joint genomic analyses open up exciting avenues to identify mechanisms underlying this intricate battle. This thesis presents two studies that leveraged paired human and pathogen genomic data from chronic hepatitis B and tuberculosis patients. By scanning for signatures of coevolution through the joint analysis of host and pathogen genomes, the studies highlight host-pathogen interaction mechanisms that the pathogens exploit to evade human immunity and natural resistance. Next, I present a novel approach, which was applied to the tuberculosis study, to improve genotype imputation in populations that are underrepresented in genomics resources. Finally, I present a generalizable workflow that could be adopted by the research community to conduct host-pathogen genomic studies on other infectious diseases. Overall, the studies reveal novel insights into the evasion mechanisms that pathogens employ in hepatitis B and tuberculosis, which could be relevant for developing novel therapeutics and vaccines. Furthermore, they establish the potential of joint genomic analyses to extend our understanding of host-pathogen interaction and provide the framework for further studies, especially in underrepresented populations where the burden of infectious diseases is often the highest.encoevolutionhost-pathogen interactiongenomicshepatitis Btuberculosisinfectious diseasesgenome-to-genomethesis::doctoral thesis