Clinical Genome Resource (ClinGen)

项目总结/摘要（总体） 我们在这里建议继续我们的工作，为策展创造世界上最好的社区资源， 通过制定与临床护理有关的遗传变异知识， 临床基因组（ClinGen）资源。ClinGen的目标可以通过回答以下相关问题来总结： 基因变异导致疾病的证据（基因有效性），疾病基因内的特定变异是 与疾病相关（变异分类），以及是否有证据表明需要采取特定的临床行动， 发现变体（可操作性）。作为提交U41申请的三个赠款的一部分，我们的团队将有一个 特别关注ClinGen过程的实施，以在非经典的 孟德尔疾病，包括遗传性癌症、癌症中的体细胞变异、药物基因组学和复杂 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 通过引入不断增加的序列来分析这些变异体， 来自不同人群的基因分型数据集。我们还将探讨围绕报告的复杂问题， 临床基因组学中的祖先，特别是不同环境中的等位基因可能具有不同的疾病影响。 在ClinGen资助斯坦福大学/贝勒信息学和计算生物学团队的第一阶段， 已经为基因、变异和可操作性策展建立了许多策展界面。在本申请中，我们 我计划扩展一套在线资源，这些资源可以无缝地聚合、规范化和呈现不同的 证据的来源。我们的目标是实现一致的治疗和改善临床应用 基因组数据在医学上的应用。我们将为社区提供培训 通过促进在线学习课程，支持临床领域工作组， 并建立了帮助台。clinicalgenome.org在线公共门户网站将提供这些活动的结果。 社区分析，用于临床解释和临床实践指南的制定 基于遗传学的结果。

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.