Project Summary New solutions are desperately needed to reduce the annual global burden of dengue. As we are currently witnessing for SARS-CoV-2, virus genomics can be harnessed to directly inform public health control measures. For most other pathogens, including dengue virus, we do not have the depth of genomic information for these uses. For dengue virus, part of the issue is its complexity: it is comprised of four genetically distinct serotypes with many defined genotypes and even more undefined variants. Furthermore, our current surveillance and research programs are not set up to fully take advantage of virus genomics. In this proposal, I will address the major barriers for modernizing dengue virus genomic programs: (1) development of a universal-dengue virus whole genome sequencing approach utilizing the framework being established globally for SARS-CoV-2; (2) formation of a collaborative network in the underserved region of the Caribbean to uncover the circulating dengue virus diversity and provide local training and sequencing support; (3) utilization of travel surveillance to provide information from beyond the network to serve as a template for other genomic surveillance systems; (4) development of a new dengue virus genetic classification system to more easily identify variants of concern/interest and to better utilize the genomic data without needing complex phylogenetic analysis; (5) creation of a webtool to provide easy access to the variant classification system, detailed regional and county-level analysis, genomic data, and protocols; and (6) detailed phylogenetic analysis to uncover key epidemiological processes, like the outbreak emergence interval and patterns of spread, to aid in future disease forecasting. Completion of the goals outlined in this proposal would significantly advance our knowledge and assessment of dengue virus diversity, evolution, and epidemiology. Researchers will be able to capitalize on these data and tools to facilitate the innovation of genomics-informed control strategies.