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: 10670968
• 负责人: TERI Ellen KLEIN
• 金额: $ 530.1万
• 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/10670968
• 关键词: Achievement; Adult; Alleles; Autoimmune Diseases; Automation; Childhood; Classification; Clinical; Code; Communities; Complex; Consumption; Data; Data Set; Databases; Development; Diagnostic; Disease; Ecosystem; Education; Ensure; Ethnic Origin; FAIR principles; Gene Frequency; Genes; Genome; Genomic medicine; Genomics; Genotype; Goals; Guidelines; Hereditary Malignant Neoplasm; Human Genetics; Human Genome; Informatics; Infrastructure; Inherited; Institution; International; Internet; Knowledge; Lead; Link; Literature; Malignant Neoplasms; Measures; Medical Genetics; Medicine; Modeling; Participant; Pilot Projects; Policies; Population Heterogeneity; Procedures; Process; Race; Registries; Research; Research Proposals; Resources; Rheumatism; Risk; Source; Specific qualifier value; Structure; Technology; Training; Training and Education; Universities; Untranslated RNA; Variant; Work; base; clinically relevant; college; data hub; data modeling; data sharing; design; diverse data; empowerment; forging; genetic variant; genome resource; genomic data; human disease; improved; innovation; interoperability; knowledge curation; knowledgebase; member; novel; outreach; phenotypic data; polygenic risk score; programs; response; scale up; software infrastructure; software systems; tool; tool development; trustworthiness; web based software; 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).

项目总结/摘要 临床基因组资源（ClinGen）是一个重要的社区资源， 基因组知识哈佛/盖辛格、凯泽和贝勒大学的三个研究小组 自2013年以来，医学/斯坦福大学一直在合作创建成功的框架和软件 人类基因组的持续管理系统。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， 创新的基因组管理计划。ClinGen的策略非常成功：创建培训， 为国际专家小组（1400多名成员）提供框架和监督，同时产生动态用户- 知情的公共工具，包括ClinGen Curation Interfaces，Allele Registry和Linked Data Hub。这多- 贝勒医学院和斯坦福大学响应PAR-20 - 100的机构申请 基因组社区资源，以支持我们不断发展的创新先进的网络 用于软件基础设施的技术，支持ClinGen的基因，变异和可操作性策展工作。 在这个应用中，我们寻求大规模操作，产生高通量的程序和信息学。 跨ClinGen领域的策展。我们提出了多项改进措施，通过简化 基因组和表型数据的聚合和连接，包括来自不同人群的数据（目标1） 基因和变体策展（目标2）和可操作性策展（目标3）的半自动化。我们期待新的 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， 新的策展方法，包括多基因风险评分（PRS）的策展和复杂的模型策展， HLA相关的风湿性和自身免疫性疾病中的疾病（目的4）。我们开发了创新的 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员工和ClinGen管理知识用户的多样性（目标5）。

项目成果

Evolution of germline TP53 variant classification in children with cancer.

• DOI: 10.1016/j.cancergen.2022.02.011
• 发表时间: 2022-06
• 期刊: CANCER GENETICS
• 影响因子: 1.9
• 作者: Tallis, E.;Scollon, S.;Ritter, D. I.;Plon, S. E.
• 通讯作者: Plon, S. E.

tmVar 3.0: an improved variant concept recognition and normalization tool.

• DOI: 10.1093/bioinformatics/btac537
• 发表时间: 2022-09-15
• 期刊: Bioinformatics (Oxford, England)

Optimising clinical care through CDH1-specific germline variant curation: improvement of clinical assertions and updated curation guidelines.

• DOI: 10.1136/jmg-2022-108807
• 发表时间: 2023-06
• 期刊: Journal of medical genetics
• 影响因子: 4

Integrating somatic variant data and biomarkers for germline variant classification in cancer predisposition genes.

• DOI: 10.1002/humu.23640
• 发表时间: 2018-11
• 期刊: Human mutation
• 影响因子: 3.9
• 作者: Walsh MF;Ritter DI;Kesserwan C;Sonkin D;Chakravarty D;Chao E;Ghosh R;Kemel Y;Wu G;Lee K;Kulkarni S;Hedges D;Mandelker D;Ceyhan-Birsoy O;Luo M;Drazer M;Zhang L;Offit K;Plon SE
• 通讯作者: Plon SE