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

基本信息

批准号：
10595197
负责人：
BRUCE E BOWLER
金额：
$ 6.1万
依托单位：
UNIVERSITY OF MONTANA
依托单位国家：
美国
项目类别：
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/10595197
关键词：
2019-nCoV Age Award Base Sequence Bioinformatics COVID-19 detection COVID-19 pandemic COVID-19 surveillance COVID-19 testing Centers of Research Excellence Clinic Communities Data Data Analyses Databases Demography Diagnostic Epidemiology Ethnic Origin Evolution Frequencies Future Genetic Genetic Models Genetic Recombination Genetic Structures Genetic Variation Genome Genomics Geographic Locations Geography Grant Health Hospitals Human Immune Immunologics Infrastructure Knowledge Modeling Molecular Molecular Evolution Monitor Montana Mutation National Institute of General Medical Sciences Natural Selections Patients Pattern Pharmacogenetics Phase Play Population Population Genetics Public Health Research Resistance Resources Role Rural Rural Community SARS-CoV-2 genome SARS-CoV-2 transmission SARS-CoV-2 variant Sampling Series Services Shapes Site Structure Testing Time Universities Variant Viral Virulence Virus base clinical diagnostics fitness genetic analysis genome sequencing genomic variation host-microbe interactions insight metropolitan molecular sequence database novel novel vaccines pandemic disease repository rural area sex success surveillance data theories trend tribal Nation tribal health variants of concern whole genome working group

项目摘要

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.

项目概要蒙大拿州是一个幅员辽阔、以农村为主的州，自建国之初就有 12 个部落国家。 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这占蒙大拿州和过去 11 个月所有公开可用的 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，在包含部落国家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。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跨越城乡鸿沟的 SARS-CoV-2 多样性和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我们团队的多样性在州和地区内采样的遗传多样性系列模式的演变。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 变化的比较现有数据的广度允许集中于跟踪存在和变化的分析。跨城乡界限的已知 SARS-CoV-2 变体的频率，同时还监测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，提出了新的变异。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以塑造 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。