Clinical Genome Resource (ClinGen)

项目摘要/摘要(总体) 我们建议在这里继续我们的工作，创造世界上最好的社区资源的策展和 传播与临床护理有关的遗传变异知识 临床基因组(Clingen)资源。克林根的目标可以通过回答与以下方面相关的问题来概括 基因变异导致疾病的证据(基因有效性)，疾病基因中的特定变异是 与疾病相关(不同的分类)以及是否有证据表明有特定的临床行动 发现了变种(可操作性)。作为提交U41申请的三个助学金的一部分，我们的团队将有一个 特别关注对非经典基因和变异体的Clingen过程的实施 孟德尔疾病包括遗传性癌症、癌症中的体细胞变异、药物基因组学和复合体 遗传包括常见疾病中的非编码变异。我们还建议进一步丰富 通过引入不断递增的序列和 来自不同人群的基因分型数据集。我们还将探讨有关报告的复杂问题 在临床基因组学中，祖先尤其是等位基因在不同的背景下可能会对疾病产生不同的影响。 在克莱根资助斯坦福/贝勒信息学和计算生物学团队的第一阶段 建立了多个针对基因、变异和可操作性的库管理界面。在此应用程序中，我们 计划扩展无缝聚合、标准化和呈现完全不同的在线资源套件 向馆长提供证据来源。我们的目标是实现一致的治疗和改善临床应用 通过这个信息学基础设施对医学中的基因组数据进行分析。我们将为社区提供培训 在使用这些工具方面，通过促进在线学习课程，支持临床领域工作组 和创建服务台。Clinicalgenome.org在线公共门户网站将提供这些结果 社区用于临床解释和制定临床实践指南的分析 这是基于基因结果。

PROJECT SUMMARY/ABSTRACT (OVERALL) We propose here to continue our work to create the world’s best community resource for the curation and dissemination of knowledge on genetic variations relevant to clinical care through the development of the Clinical Genome (ClinGen) Resource. ClinGen’s goals can be summarized by answering questions related to the evidence that variation in a gene causes disease (gene validity), specific variants within a disease gene are associated with disease (variant classification) and whether there is evidence for specific clinical actions if such variants are found (actionability). As part of the three grants submitting U41 applications, our team will have a particular focus on implementation of ClinGen processes for gene and variant curation across non-classic Mendelian disorders including hereditary cancer, somatic variation in cancer, pharmacogenomics and complex inheritance including non-coding variation in common disease. We are also proposing to further enrich the analysis of these variants across populations by the introduction of the ever increasing sequence and genotyping datasets from diverse populations. We will also explore the complex issues around reporting of ancestry in clinical genomics particularly as alleles in different settings may have different disease impact. During the first phase of ClinGen funding the Stanford/Baylor informatics and computational biology teams have built a number of curation interfaces for gene, variant and actionability curation. In this application we plan to expand the suite of online resources that seamlessly aggregates, normalizes and presents disparate sources of evidence to curators. Our goal is to enable consistent curation and improve the clinical application of genomic data in medicine through this informatics infrastructure. We will provide training for the community in the use of these tools by facilitating online learning courses, support of the clinical domain working groups and creation of helpdesks. The clinicalgenome.org online public portal will provide the outcome of these analyses for the community to utilize for clinical interpretation and development of clinical practice guidelines that are based on genetic results.