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

项目摘要 蒙大拿州是一个地理上很大的州，主要是农村，有12个部落。较年初 在2021年春季的SARS-CoV-2大流行中，蒙大拿州在全国范围内的代表性严重不足， 测序数据库-特别是在农村地区-限制了国家跟踪和控制 在城乡之间蔓延。在NIGMS的支持下，UM COBRE生物分子中心 结构和动力学（CBSD）与蒙大拿州公共卫生与人类服务部合作 （DPHHS）和其他区域卫生合作伙伴将在2015年对2，650多个SARS-CoV-2全基因组进行测序。 过去11个月这代表了蒙大拿州所有公开可用的SARS-CoV-2序列数据的约20%， 导致蒙大拿州现在在国家测序数据库中的比例过高， 在包含部落民族的主要农村地区进行更深入的采样。不同时间序列的可用性 过去一年中产生的基因组数据为填补以下知识的关键空白提供了机会： SARS-CoV-2多样性和城乡差异的演变。转向分析密集型阶段， 该项目，这一补充CBSD COBRE赠款将继续支持全基因组测序的 新的病例，同时还开发复杂的群体遗传模型，以严格测试适应性病毒 在国家和地区内采样的遗传多样性的系列模式的演变。我们的团队是多元化的 生物信息学、群体遗传学、宿主-微生物相互作用和药物遗传学方面的专业知识将使 我们模拟了蒙大拿州SARS-CoV-2基因组变异与全球SARS-CoV-2变化的比较 时间的多样性。现有数据的广度允许分析集中于跟踪存在， 在城乡分界线上关注的已知SARS-CoV-2变异的频率，同时还监测 新的变种。通过利用我们在基因组学和群体遗传学方面的独特专长， 研究将建立分析框架和模型，重点是揭示人口统计学和自然 选择相互作用塑造SARS-CoV-2基因组进化。这一补充将通过 第三阶段CBSD COBRE奖，有三个具体目标： 研究目标1：蒙大拿州社区SARS-CoV-2变异的遗传结构是什么？ 时间和如何比较这种变化的区域，国家和全球SARS-CoV-2多样性？ 研究目标2：在农村和非农村地区流行的SARS-CoV-2变异体的遗传组成是否不同？ 蒙大拿州的大城市 目的3：局部或区域频率显著升高的突变是否反映了适应性病毒 进化？ 总的来说，该项目将为SARS-CoV-2在农村州的传播动态提供重要的新见解， 同时开发可被全球监测组织广泛应用的复杂分析模型。

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.