Towards a new paradigm linking virus molecular evolution and pathogenesis: experimental design and phylodynamic inference.

Phylogenetic analysis has become a powerful tool for the investigation of evolution at a molecular level. During the last three decades, statistical phylogenetics has increasingly been applied to the study of microbial pathogens. The new field of phylodynamics was formally introduced in 2004 and encompasses the interaction between evolutionary and ecological processes that shape the spatiotemporal and phylogenetic patterns of infectious disease dynamics. This novel framework has significantly enhanced the study of measurable evolving pathogen populations, in particular RNA viruses and retroviruses. One of the major challenges in phylodynamic studies, however, is the generation of data in the form of dense coverage in sequence sampling coupled with high quality epidemiological and/or accurate clinical information. This review focuses specifically on experimental and data assembling strategies that are required to test multi-level phylodynamic hypotheses, ranging from intra-host viral evolution to population dynamics of infectious disease pandemics. Ultimately, bridging the gap between rational experimental design and phylodynamic inference will prove to be essential to take full advantage of this new exciting area of research.