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

项目摘要/摘要 临床基因组资源(Clingen)是开发与临床相关的基本社区资源 基因组知识。哈佛大学盖辛格分校、北卡罗来纳大学凯撒分校和贝勒商学院的三个研究团队 医学/斯坦福大学自2013年以来一直合作创建成功的框架和软件 可持续管理人类基因组的系统。2018年FDA认可的里程碑式成就 作为第一个公开的人类基因变异数据库，Clingen作为 创新的基因组管理计划。克莱根的策略非常成功：创建培训， 国际专家小组的框架和监督(1400多名成员)，同时产生动态的用户- 知情的公共工具，包括Clingen Curation接口、Allele注册表和链接数据中心。这个多- 贝勒医学院和斯坦福大学回应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 支持克林根基因、变种和可操作性管理工作的软件基础设施技术。 在这一应用中，我们寻求规模化运营，为高吞吐量生成程序和信息学 跨Clingen域的管理。我们提出了多项改进建议，以通过精简来扩展我们的工作 基因组和表型数据的汇总和连接，包括来自不同种群的数据(目标1) 基因和变异体管理的半自动化(目标2)和可操作性管理(目标3)。我们期待着新的 临床基因组学方面，包括遗传性和躯体肿瘤变异分类标准，锻造 新的管理方法，包括多基因风险评分的管理和复合体的模型化管理 人类白细胞抗原相关风湿病和自身免疫性疾病的疾病(目标4)。我们开发了创新的 适当利用临床基因组学祖先和多样性的框架，同时努力扩大 Clingen工作人员和Clingen用户的多样性策划了知识(目标5)。

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).