Production Core

项目摘要 尽管人类遗传学领域的知识自1960年以来已经大大增加， 尽管人类基因组计划，我们仍然没有完全理解基因组的所有方式， 变异有助于人类健康和疾病。该提案代表了三个方面之一 链接U41应用程序，以继续支持临床基因组资源（ClinGen; www.clinicalgenome.org）。ClinGen项目的主要目标是支持 所有利益攸关方将基因组和健康数据存入公共领域，包括 患者，临床医生，实验室和研究人员，开发方法和信息学 基础设施，以回答数据的关键问题（策展），并创建一个基因组 知识库，使这些信息可用于社区，以改善患者 在乎我们将该提案分为五个总体目标，以实现ClinGen的目标：1） 数据共享，2）解释基因和变异的标准化方法，3）软件 和信息学基础设施，以支持和加强解释，4）社区驱动 策展和解释的努力，以及5）外展，以最大限度地发挥ClinGen的影响 resource.为了向公众提供高质量的基因组变异数据，我们将建立 我们在第一次融资期间开发的标准，经验和基础设施 期我们将利用与临床实验室的合作关系， 捕获数百万个基因测序测试产生的临床级解释 通过常规的患者临床护理过程。所有基因组变异及其 将继续通过我们的伙伴关系提交并提供解释 与NIH国家生物技术信息中心（NCBI）的ClinVar数据库进行比较。 我们还将通过以下途径收集表型数据， GenomeConnect，ClinGen的患者登记处，用于进行基因检测的个人。 ClinGen将使用这些共享的基因组和健康信息来回答关键问题 关于基因/疾病临床有效性与人类健康和疾病的相关性 关联性、变异致病性和临床可操作性。临床领域工作组 （CDWG）和专家小组（EP）将使疾病专家能够策划基因组， 作为ClinGen项目的一部分开发的方法的变体。最后，我们将 ClinGen知识库可通过 开发“临床医生友好”的用户界面 并通过新开发的ClinGen EHR App支持自动EHR更新 到 通过基因组医学提高患者护理质量。

PROJECT SUMMARY Although knowledge in the field of human genetics has greatly increased since the time of the Human Genome Project, we still do not fully understand all of the ways in which genomic variation contributes to human health and disease. This proposal represents one of three linked U41 applications to continue support for the Clinical Genome Resource (ClinGen; www.clinicalgenome.org). The main goals of the ClinGen project are to support the deposition of genomic and health data into the public domain by all stakeholders, including patients, clinicians, laboratories, and researchers, develop methods and an informatics infrastructure to answer critical questions of the data (curation), and create a genomic knowledge base that makes this information available to the community for improved patient care. We have structured this proposal into five overarching aims to meet ClinGen's goals: 1) data sharing, 2) standardized approaches to interpretation of genes and variants, 3) software and informatics infrastructure to support and enhance interpretation, 4) community-driven efforts for curation and interpretation, and 5) outreach to maximize the impact of the ClinGen resource. To make high-quality genomic variant data available to the public, we will build upon the standards, experience and infrastructure we have developed during our first funding period. We will capitalize on our collaborative relationships with clinical laboratories to capture the clinical-grade interpretations of millions of genetic sequencing tests generated through the course of routine patient clinical care. All genomic variants and their interpretations will continue to be submitted to and made accessible through our partnership with the ClinVar database within NIH's National Center for Biotechnology Information (NCBI). We will also help to augment the genomic data with phenotype data collected through GenomeConnect, ClinGen's patient registry for individuals who have had genetic testing. ClinGen will use this shared genomic and health information to answer critical questions regarding relevance to human health and disease around clinical validity for gene/disease associations, variant pathogenicity and clinical actionability. Clinical Domain Working Groups (CDWG) and Expert Panels (EP) will enable disease experts to curate sets of genes and variants following approaches developed as part of the ClinGen project. Finally, we will make the ClinGen knowledge base widely available by developing “clinician-friendly” user interfaces and supporting automatic EHR updates through the newly developed ClinGen EHR App to improve the quality of patient care through genomic medicine.