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

项目总结/摘要 关于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。 药临床护理的所有方面都来源于关于病因学、自然史和 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， 关于基因和变异的精心策划和专业裁定的知识是至关重要的。ClinGen资源 代表了遗传学界的高度合作努力，以建立一个基于证据的资源， 评估基因和变异的临床相关性，这些基因和变异易于获得（并受其信任） 诊断实验室、供应商和患者。我们的目标是通过加强和 使用创新方法加速临床基因组的治疗，以克服挑战并解决 新的话题我们将通过共同努力实现以下目标来实现这一目标： 结构化证据的遗传条件和基因和变异，导致他们;应用 临床有效性，变异致病性和遗传性的临床可操作性的专家治疗框架 条件;广泛传播有关临床相关的工具、标准、知识库和声明 基因和变异;并评估这项工作的各个方面，以便我们能够提高质量和影响， 实现透明、可重复和循证的基因组医学的资源。的 该提案在几个方面都是创新的。它将汇集尖端技术产生的数据， 注释工具，通过社区策展实现众包，并应用先进的自然语言 处理注释，以便人类策展人可以在其技能水平的顶部工作。它将利用 一个庞大而热情的志愿者社区的参与，从而成为NIH的力量倍增器 资助团队。它将让能够在其专业领域开展外联活动的倡导者参与， 将ClinGen产品的范围扩展到基因组医学研究和临床护理。它将改变一个广泛的 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， 记录出处，并注意确保资源与不同目的的互操作性， 用户，包括电子健康记录。拟议的资源项目意义重大，因为其整体 将改善，规模，并传播免费提供的专家策展和人类的解释， 基因组的全球基因组学社区，以改善所有人的医疗保健的目标。

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.