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.

项目总体概要 2019 年 12 月在中国首次发现的新型冠状病毒 SARS-CoV-2 现已传播 全球。德克萨斯医疗中心位于德克萨斯州休斯顿，美国第四大城市，位列全美前 10 名。 种族多样性对这一流行病采取了积极的早期应对措施，主要集中在急症护理上。之内 贝勒医学院，TMC - 传染病基因组中心 (TMC-GCID) 项目成员 （https://gcid.research.bcm.edu/overview）正在利用现有的基础设施，以及积极和 与临床和社区测试相关的强大样本收集流，以表征 SARS-CoV-2 整个地区的毒力和易感性。此申请请求向 TMC-GCID 提供补充资金 帮助支持 SARS-CoV-2 社区范围内的监测、完整的病毒基因组测序、鼻咽 微生物组分析和目标宿主遗传分析。本补充的主要目标是 这是由基础科学家和医学科学家组成的多学科、综合团队的共同努力取得的成果 具有良好的合作记录，并且已经在实现 TMC-GCID 的主要目标。这 我们 GCID 补充品的总体目标是研究 SARS-CoV-2 感染的生物学、宿主和 与疾病相关的微生物遗传学，并满足社区需求，特别是在 服务不足的社区，通过以下目标： i) 扩大可操作的紧急用途 授权 - (EUA-) 和符合 IRB 标准的 COVID-19 qPCR 筛查/监测计划 在线登记和同意以及符合 HIPAA 标准的结果返回，ii) 排序和分析 从 TMC 和周边地区收集的感染个体的全长 SARS-CoV-2 基因组 区域，iii) 识别可预测 COVID-19 疾病严重程度和/或的微生物共定殖/共感染 结果，iv) 表征宿主遗传变异的病毒滴度、疾病严重程度和 COVID-19 阳性患者的结果，包括人类白细胞抗原 (HLA) 的多态性， 血管紧张素转换酶 2 (ACE2) 和自然杀伤细胞免疫球蛋白样受体 (KIR) 地区。该补充品将利用最先进的高通量测序策略和 由 TMC-GCID 测序技术 (ST) 核心提供的技术，用于生成发现、数据、 将通过以下方式对传染病界进行分析和传播的工具和试剂 TMC-GCID 数据管理分析和资源传播 (DMARD) 核心。结果将是 对 SARS-CoV-2 感染中的宿主和微生物进行全面的遗传分析，揭示病原体遗传 与个体宿主反应表型相关的变异将为精准医学提供信息 治疗和诊断，不仅针对 SARS-CoV-2，还针对我们已经掌握的其他大流行威胁 观察到深刻改变我们周围的世界。