Surveillance genome sequencing to detect SARS-CoV-2 virus variants in Montana

Project Summary Montana is a geographically large and predominantly rural state with 12 Tribal nations. From the beginning of the SARS-CoV-2 pandemic through the spring of 2021, Montana was severely under-represented in national sequencing databases-and specifically in rural areas-limiting the state's ability to track and control the pandemic across the urban-rural divide. With NIGMS support, the UM COBRE Center for Biomolecular Structure and Dynamics (CBSD) teamed with the Montana Department of Public Health & Human Services (DPHHS) and other regional health partners to sequence over 2,650 whole SARS-CoV-2 genomes over the last 11 months. This represents ~20% of all publicly-available SARS-CoV-2 sequence data from Montana and has resulted in Montana now being proportionally over-represented in national sequencing databases, with deeper sampling in predominantly rural areas that contain Tribal nations. The availability of diverse time-series genome data produced over the last year provides the opportunity to now fill critical gaps in knowledge about SARS-CoV-2 diversity and evolution across the urban-rural divide. Shifting to an analysis-intensive phase of the project, this supplement to the CBSD COBRE grant will continue to support whole genome sequencing of new cases while also developing sophisticated population genetic models to rigorously test for adaptive viral evolution across serial patterns of genetic diversity sampled within the state and the region. Our team's diverse expertise in bioinformatics, population genetics, host-microbe interactions, and pharmacogenetics will enable us to model how SARS-CoV-2 genomic variation in Montana compares to changes in global SARS-CoV-2 diversity through time. The breadth of existing data allows for analyses focused on tracking the presence and frequency of known SARS-CoV-2 variants of concern across the urban-rural divide, while also surveilling for new variants. By leveraging our unique expertise in phylogenomics and population genetics, the proposed research will establish analytical frameworks and models focused on unraveling how demography and natural selection interact to shape SARS-CoV-2 genome evolution. This supplement will be implemented through the phase III CBSD COBRE award and has three specific aims:  Aim 1: What is the genetic structure of SARS-CoV-2 variation across Montana communities through time and how does this variation compare to regional, national, and global SARS-CoV-2 diversity?  Aim 2: Does the genetic composition of circulating SARS-CoV-2 variants differ between rural versus metropolitan communities in Montana?  Aim 3: Do mutations with significantly elevated local or regional frequencies reflect adaptive viral evolution? Overall, the project will provide critical new insights into the dynamics of SARS-CoV-2 spread in a rural state, while developing sophisticated analytical models that can be broadly applied by global surveillance groups.