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

监测基因组测序以检测蒙大拿州的 SARS-CoV-2 病毒变异

• 批准号: 10684476
• 负责人: BRUCE E BOWLER
• 金额: $ 67.07万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-10 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684476
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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.

项目概要 蒙大拿州幅员辽阔，以农村地区为主，有 12 个部落国家。从一开始 2021 年春季 SARS-CoV-2 大流行期间，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基因组测序的能力 疫情跨越城乡鸿沟。在 NIGMS 的支持下，UM COBRE 生物分子中心 结构与动力学 (CBSD) 与蒙大拿州公共卫生与公众服务部合作 (DPHHS) 和其他区域卫生合作伙伴对超过 2,650 个 SARS-CoV-2 完整基因组进行了测序 过去 11 个月。这占蒙大拿州和美国所有公开可用的 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所占比例过高， 在包含部落民族的主要农村地区进行更深入的抽样。不同时间序列的可用性 去年产生的基因组数据为现在填补有关知识的关键空白提供了机会 SARS-CoV-2 的多样性和跨越城乡差异的进化。转向分析密集阶段 该项目，对 CBSD COBRE 赠款的补充将继续支持全基因组测序 新病例，同时还开发复杂的群体遗传模型来严格测试适应性病毒 在州和地区内采样的遗传多样性系列模式的进化。我们的团队多元化 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 我们模拟蒙大拿州 SARS-CoV-2 基因组变异与全球 SARS-CoV-2 变化的比较 随着时间的推移呈现多样性。现有数据的广度允许集中于跟踪存在和 跨城乡界限的已知 SARS-CoV-2 变体的频率，同时还监测 新的变种。通过利用我们在系统基因组学和群体遗传学方面的独特专业知识，拟议的 研究将建立分析框架和模型，重点揭示人口学和自然 选择相互作用塑造 SARS-CoV-2 基因组进化。该补充将通过 第三阶段 CBSD COBRE 奖项具有三个具体目标： 目标 1：蒙大拿州社区中 SARS-CoV-2 变异的遗传结构是什么？ 时间以及这种差异与区域、国家和全球 SARS-CoV-2 多样性相比如何？ 目标 2：农村地区和农村地区传播的 SARS-CoV-2 变异体的基因组成是否存在差异？ 蒙大拿州的大都市社区？ 目标 3：局部或区域频率显着升高的突变是否反映了适应性病毒 进化？ 总体而言，该项目将为农村地区 SARS-CoV-2 传播动态提供重要的新见解， 同时开发可供全球监测组织广泛应用的复杂分析模型。