GENOMIC APPROACHES TO UNDERSTAND DISEASE SUSCEPTIBILITY AND PATHOGENESIS OF SARS-COV-2

了解 SARS-COV-2 疾病易感性和发病机制的基因组学方法

• 批准号: 10172492
• 负责人: RICHARD A GIBBS
• 金额: $ 10万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10172492
• 关键词: 2019-nCoV; Address; Age; Area; Authorization documentation; Biology; COVID-19; China; Cities; Clinical; Clonal Expansion; Code; Collaborations; Collection; Communicable Diseases; Communities; Consent; Country; DNA Sequence; Data; Detection; Development; Diagnostic; Disease; Disease susceptibility; Emergency Situation; Enrollment; Ensure; Funding; Future; Gender; General Population; Genetic Polymorphism; Genetic Variation; Genome; Genomic Centers for Infectious Diseases; Genomic approach; Goals; HLA Antigens; Health Insurance Portability and Accountability Act; High-Throughput Nucleotide Sequencing; Immune response; Immunoglobulins; Individual; Infection; Infrastructure; Institutional Review Boards; Length; Link; Medical center; Medicine; Metadata; Methods; Microbe; Microbial Genetics; Natural Killer Cells; Outcome; Pathogenesis; Patients; Peptidyl-Dipeptidase A; Phenotype; Physicians; Predisposition; Protocols documentation; Reagent; Recombinant DNA; Request for Applications; Research; Resources; Reverse Transcriptase Polymerase Chain Reaction; Role; Sampling; Scientist; Sequence Analysis; Severity of illness; Shotguns; Specimen; Speed; Stream; Surveillance Program; Symptoms; Technology; Testing; Texas; Therapeutic; Time; United States; Variant; Viral; Viral Genome; Virulence; Virus; acute care; base; co-infection; college; comorbidity; cost; data management; data tools; experience; genetic analysis; genetic profiling; genetic variant; genome sequencing; infection rate; innovation; member; metropolitan; microbial; microbiome; multidisciplinary; novel coronavirus; novel diagnostics; novel therapeutics; pandemic disease; pathogen; precision medicine; programs; racial diversity; receptor; reconstruction; repository; response; sample collection; screening; viral RNA; virome; virus genetics; whole genome

OVERALL PROJECT SUMMARY The novel coronavirus, SARS-CoV-2, that was first detected in China in December 2019 has now spread globally. The Texas Medical Center in Houston, TX, the fourth largest city in the US, and among the top 10 in racial diversity, mounted an aggressive early response to the pandemic, primarily focused on acute care. Within Baylor College of Medicine, members of the TMC - Genomic Center for Infectious Disease (TMC-GCID) program (https://gcid.research.bcm.edu/overview) are leveraging existing infrastructure, together with an active and robust sample collection stream linked to both clinical and community testing, to characterize SARS-CoV-2 virulence and susceptibility across the region. This application requests supplemental funding to the TMC-GCID to help support SARS-CoV-2 community-wide surveillance, complete viral genome sequencing, nasopharyngeal microbiome profiling, and targeted host genetic analyses. The primary objective of this supplement will be achieved through the collaborative efforts of a multidisciplinary, integrated team of basic and physician scientists with a track-record of collaboration and who are already delivering on the primary goals of the TMC-GCID. The overall goals of our GCID supplement is to study the biology of SARS-CoV-2 infection, the host and microbial genetics associated with disease, and to address community needs, particularly in underserved communities, through the following aims: i) expand an operational Emergency Use Authorization- (EUA-) and IRB-compliant COVID-19 qPCR screening/surveillance program featuring online enrollment and consent as well as HIPAA-compliant return of results, ii) sequence and analyze full-length SARS-CoV-2 genomes from infected individuals collected from the TMC and surrounding area, iii) identify microbial co-colonization/co-infections that predict COVID-19 disease severity and/or outcome, iv) Characterize the host genetic variation with respect to viral titer, disease severity, and outcome in patients positive for COVID-19, including polymorphisms in human leukocyte antigen (HLA), angiotensin-converting enzyme 2 (ACE2), and natural killer cell immunoglobulin-like receptor (KIR) regions. This supplement will leverage the cutting edge, high-throughput sequencing strategies and technologies supplied by the TMC-GCID Sequencing Technology (ST) Core, in generating discoveries, data, tools, and reagents that will be analyzed and disseminated to the infectious disease community through the TMC-GCID Data Management Analysis and Resource Dissemination (DMARD) Core. The result will be a comprehensive genetic profiling of hosts and microbes in SARS-CoV-2 infection that will reveal pathogen genetic variants associated with individual host response phenotypes that will inform precision medicine-based therapeutics and diagnostics, not just for SARS-CoV-2, but for other pandemic threats that we have already observed to profoundly change the world around us.

总体项目摘要 2019年12月在中国首次发现的小说冠状病毒SARS-COV-2现已蔓延 全球。德克萨斯州休斯敦的德克萨斯医疗中心是美国第四大城市，也是十大 种族多样性，对大流行的早期反应产生了积极的早期反应，主要集中于急性护理。之内 贝勒医学院，TMC - 基因组传染病中心（TMC -GCID）计划的成员 （https://gcid.research.bcm.edu/overview）正在利用现有基础架构以及一个活动 与临床和社区测试链接的强大样本收集流，以表征SARS-COV-2 整个地区的毒力和敏感性。该申请要求向TMC-GCID补充资金 为了帮助支持SARS-COV-2社区范围的监视，完整的病毒基因组测序，鼻咽 微生物组分析和靶向宿主遗传分析。该补充的主要目标将是 通过基础和医师科学家组成的综合团队的合作努力来实现 凭借合作的田径记录，并且已经实现了TMC-GCID的主要目标。这 我们GCID补充剂的总体目标是研究SARS-COV-2感染，宿主和 与疾病相关的微生物遗传学，并满足社区需求，尤其是在 通过以下目的，服务不足的社区：i）扩大操作紧急使用 授权 - （EUA-）和符合IRB的COVID-19 QPCR筛查/监视计划的特征 在线注册和同意以及符合HIPAA结果的结果，ii）序列和分析 来自TMC和周围收集的感染个体的全长SARS-COV-2基因组 区域，iii）确定微生物共殖民化/共同感染，以预测COVID-19的疾病严重程度和/或 结果，iv）表征宿主遗传变异相对于病毒滴度，疾病严重程度和 COVID-19的患者的结果，包括人白细胞抗原（HLA）的多态性， 血管紧张素转换酶2（ACE2）和天然杀手型细胞类似球蛋白样受体（KIR） 地区。该补充剂将利用最前沿，高通量测序策略和 TMC-GCID测序技术（ST）核心提供的技术在生成发现，数据， 工具和试剂将通过 TMC-GCID数据管理分析和资源传播（DMARD）核心。结果将是 SARS-COV-2感染中宿主和微生物的全面基因分析，这将揭示病原体遗传 与单个宿主响应表型相关的变体，这些表型将为基于精确的医学提供信息 治疗和诊断，不仅用于SARS-COV-2，还针对我们已经存在的其他大流行威胁 观察到深刻改变我们周围的世界。