Introduction: With increasing availability of pathogen genetic and especially whole-genome sequence data, there is a pressing need for analytical tools and innovative approaches to make use of them. In particular, methods for using genomic data to make inferences about transmission chains and pathogen evolution under selection by host immunity, vaccines, and antibiotics, are still in their infancy. These questions are fundamentally different from the types of questions asked when examining one sequence at a time, which illuminate the biology of conserved aspects of infection and pathogenesis. Population genomic studies shed light on population heterogeneity in the pathogen, its consequences and causes. These inferences naturally lend themselves to the estimation of parameters for transmission-dynamic models and, even more fundamentally, to the determination of how such models should be structured, and the testing of their predictions. To date, using MIDAS and non-MIDAS funding for analytic efforts, and non-MIDAS funding for the costs of sequencing, we have made a number of significant discoveries over the last five years using pathogen population genomics and genetics, and we have identified many opportunities to improve and expand methods over the next five years, as well as to apply existing methods to significant questions of biology and epidemiology.
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