Baylor College of Medicine/Stanford University Clinical Genome Resource (CLINGEN)

贝勒医学院/斯坦福大学临床基因组资源 (CLINGEN)

• 批准号: 10270983
• 负责人: TERI Ellen KLEIN
• 金额: $ 520.53万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10270983
• 关键词: Achievement; Adult; Alleles; Autoimmune Diseases; Automation; Childhood; Classification; Clinical; Code; Communities; Complex; Consumption; Data; Data Set; Databases; Development; Diagnostic; Disease; Ecosystem; Ensure; Ethnic Origin; FAIR principles; Gene Frequency; Genome; Genomic medicine; Genomics; Genotype; Goals; Guidelines; Hereditary Malignant Neoplasm; Human Genetics; Human Genome; Informatics; Infrastructure; Inherited; International; Internet; Knowledge; Lead; Link; Literature; Malignant Neoplasms; Measures; Medical Genetics; Medicine; Modeling; Online Systems; Participant; Pilot Projects; Policies; Population Heterogeneity; Procedures; Process; Race; Registries; Research; Research Proposals; Resources; Rheumatism; Risk; Source; Structure; Technology; Training; Training and Education; Universities; Untranslated RNA; Variant; Work; base; clinically relevant; college; data hub; data modeling; data sharing; design; forging; genetic variant; genome resource; genomic data; human disease; improved; innovation; interoperability; knowledge base; knowledge curation; member; novel; outreach; phenotypic data; polygenic risk score; programs; response; scale up; software infrastructure; software systems; tool; tool development; trustworthiness; web site; working group

Project Summary/Abstract The Clinical Genome Resource (ClinGen) is an essential community resource developing clinically relevant genomic knowledge. Three research teams at Harvard/Geisinger, UNC/Kaiser and Baylor College of Medicine/Stanford have worked collaboratively since 2013 to create successful frameworks and software systems for sustained curation of the human genome. The landmark achievement in 2018 of FDA recognition as the first Public Human Genetic Variant Database significantly increased ClinGen's prominence as an innovative genome curation program. ClinGen's strategy has been highly successful: creating the training, framework and oversight for international expert panels (over 1400 members), while generating dynamic user- informed public tools including the ClinGen Curation Interfaces, Allele Registry and Linked Data Hub. This multi- institutional application from Baylor College of Medicine and Stanford University in response to PAR-20-100 Genomic Community Resources to support our ongoing development of the innovative advanced web technologies for software infrastructure that supports ClinGen’s gene, variant and actionability curation efforts. In this application we seek to operate at scale, generating procedures and informatics for high-throughput curation across ClinGen domains. We propose multiple improvements to scale our work through streamlined aggregation and linking of genomic and phenotypic data including sources from diverse populations (Aim 1) semi-automation for gene and variant curation (Aim 2) and actionability curation (Aim 3). We anticipate new facets of clinical genomics including standards for variant classification in hereditary and somatic cancer, forging novel curation approaches including curation of polygenic risk scores (PRS) and modeling curation of complex disorders in HLA-related rheumatologic and autoimmune diseases (Aim 4). We have developed innovative frameworks for appropriate use of ancestry and diversity in clinical genomics, while in parallel working to expand the diversity of the ClinGen workforce and users of ClinGen curated knowledge (Aim 5).

项目概要/摘要 临床基因组资源 (ClinGen) 是开发临床相关的重要社区资源 哈佛大学/盖辛格学院、北卡罗来纳大学/凯撒学院和贝勒学院的三个研究团队。 Medicine/斯坦福大学自 2013 年以来一直合作创建成功的框架和软件 2018 年 FDA 认可的里程碑式成就。 作为第一个公共人类遗传变异数据库，显着提高了 ClinGen 作为 ClinGen 的创新基因组管理计划非常成功：创建培训、 国际专家小组（超过 1400 名成员）的框架和监督，同时产生动态的用户 知情的公共工具包括 ClinGen Curation Interfaces、等位基因注册表和链接数据中心。 贝勒医学院和斯坦福大学针对 PAR-20-100 的机构申请 基因组社区资源支持我们不断开发创新的高级网络 支持 ClinGen 基因、变异和可操作性管理工作的软件基础设施技术。 在此应用程序中，我们寻求大规模运营，生成高通量的程序和信息学 我们提出多项改进措施，通过精简来扩展我们的工作。 基因组和表型数据的聚合和链接，包括来自不同人群的来源（目标 1） 我们期待新的基因和变异管理（目标 2）和可操作性管理（目标 3）的半自动化。 临床基因组学的各个方面，包括遗传性和体细胞癌症的变异分类标准、锻造 新颖的管理方法，包括多基因风险评分（PRS）的管理和复杂的建模管理 HLA 相关风湿病和自身免疫性疾病的疾病（目标 4）。 在临床基因组学中适当使用祖先和多样性的框架，同时努力扩大 ClinGen 员工队伍和 ClinGen 策划知识用户的多样性（目标 5）。