The Clinical Genome Resource – Advancing genomic medicine through biocuration and expert assessment of genes and variants at scale

项目摘要/摘要 有关临床相关基因和变异的高质量证据是基因组学的基本基石 医药。临床护理的所有方面都源于关于病因、自然病史和 疾病的管理。随着基因组分析在患者护理中变得越来越常规，公共可获得性 关于基因和变异的精心策划和专业判断的知识是至关重要的。克莱根资源 代表了遗传学社区为建立基于证据的资源而做出的高度合作的努力 对易于获得(和信任)的基因和变异的临床相关性的评估 诊断实验室、提供者和患者。我们的目标是通过增强和 使用创新的方法加速临床基因组的管理，以克服挑战和解决 新话题。我们将通过共同追求以下目标来实现这一目标： 关于遗传疾病和导致这些疾病的基因和变种的结构化证据；应用 基因的临床有效性、变异致病性和临床可操作性的专家评估框架 条件；广泛传播有关临床相关的工具、标准、知识库和断言 基因和变种；以及评估这项工作的各个方面，以便我们能够提高质量和影响 实施透明、可重现和循证的基因组医学的资源。这个 这项提议在几个方面都是创新的。它将汇聚尖端技术产生的数据，适应 注释工具，通过社区管理实现众包，并应用高级自然语言 处理注释，以便人类馆长能够在他们的技能水平上发挥最大作用。它将利用 大量热情的志愿者社区的参与，从而成为国家卫生研究院的力量倍增器 资助的团队。它将吸引能够在其专业领域内开展外联活动的倡导者，以进一步 将Clingen产品的覆盖范围扩展到基因组医学研究和临床护理。它将改变一种广泛的 将一系列临床和基础科学数据转化为结构良好、透明引用的专家断言 记录来源和注意确保资源的互操作性和不同的目的-- 用户，包括电子健康记录。拟议的资源项目意义重大，因为它整体上 将改进、扩大和传播免费可用的专家对人类的管理和解释 向全球基因组学社区捐赠基因组，目标是改善所有人的医疗保健。

Project Summary/Abstract High-quality evidence about clinically relevant genes and variants is a fundamental cornerstone of genomic medicine. All aspects of clinical care derive from accurate information about the etiology, natural history, and management of disease. With genomic analysis becoming more routine for patient care, the public availability of well-curated and expertly adjudicated knowledge about genes and variants is critical. The ClinGen Resource represents a highly collaborative effort of the genetics community to establish an evidence-based resource for the assessment of the clinical relevance of genes and variants that is readily accessible to (and trusted by) diagnostic laboratories, providers, and patients. Our objective is to improve patient care through enhanced and accelerated curation of the clinical genome using innovative approaches to overcome challenges and address new topics. We will accomplish this objective through the concerted pursuit of the following aims: aggregation of structured evidence regarding genetic conditions and the genes and variants that cause them; application of frameworks for expert curation of clinical validity, variant pathogenicity, and clinical actionability of genetic conditions; broad dissemination of tools, standards, knowledge bases, and assertions about clinically relevant genes and variants; and evaluation of all aspects of this work, so that we can improve the quality and impact of the resource for implementation of transparent, reproducible, and evidence-based genomic medicine. The proposal is innovative in several ways. It will aggregate data produced by cutting edge technologies, adapt annotation tools to enable crowdsourcing through community curation, and apply advanced natural language processing for annotation so that human curators can function at the top of their skill level. It will leverage the participation of a large and enthusiastic community of volunteers, thus acting as a force multiplier for the NIH funded teams. It will engage advocates who can conduct outreach within their areas of specialty, to further extend the reach of ClinGen products into genomic medicine research and clinical care. It will transform a wide range of clinical and basic science data into well-structured, transparently referenced expert assertions with documentation of provenance and attention to ensuring the interoperability of the resource with diverse end- users, including electronic health records. The proposed resource project is significant because in its entirety it will improve, scale, and disseminate the freely available expert curation and interpretation of the human genome to the global genomics community with the goal of improving health care for all people.