A Knowledge Base for Clinically Relevant Genes and Variants

描述（由申请人提供）：人类基因组计划刺激了基因测序技术的基本进展，现在反过来又改变了基因组科学和医学。然而，由于缺乏关于基因对疾病的贡献的明确信息来源，基因组医学的前景仍然有限。尽管许多团体正试图单独解决这一差距，但如果他们仍然不联系，这些努力最终将失败。临床相关变异资源代表了遗传学社区的合作努力，为评估基因和变异的临床相关性建立了一个以证据为基础的资源。这个知识库对于自信、高效地分析和解释基因组级序列数据至关重要。其目标是提供一份公开可得的共识摘要，总结来自医学文献、基础科学研究人员和临床实验室的关于与人类健康和疾病有关的基因和变异的证据。将为研究人员、临床实验室、医生、患者和电子健康记录提供专用门户，以确保广泛访问该资源。研究人员联盟将通过追求五个具体目标来实现这一目标：1)开发一种半定量的方法来评估基因-表型对的“临床可操作性”，这将允许利益相关者团体为此类遗传结果的报告和使用提供指导；2)建立一个标准化的过程来评估变异是否良性、是否与疾病相关或是否具有不确定的意义；3)部署信息学基础设施，通过聚合来自不同来源的信息并将其呈现给人类评估来支持联盟的活动；4)组建临床领域特异性工作组，系统地评估与临床相关的基因（以及这些基因中的变异）；5)确保资源与电子病历系统的互操作性。该方法的创新之处在于开发了新的方法来评估基因和变异，这些方法是稳健的和可重复的，并通过建立一个分布式信息系统来聚合和显示信息，并具有更新和再分析的机制。该建议具有前瞻性，因为将注意确保资源与各种最终用户（包括电子健康记录）的互操作性。拟议的资源项目意义重大，因为它将以透明和循证的方式，在大量临床领域提供免费的人类基因组专家管理。

DESCRIPTION (provided by applicant): Fundamental advances in genetic sequencing technologies were stimulated by the human genome project and are now in turn transforming genome science and medicine. Yet the promise of genomic medicine remains limited by the lack of definitive sources of information about the genetic contributions to disease. Although many groups are attempting to address this gap individually, such efforts will ultimately fall shor if they remain disconnected. The Clinically Relevant Variants Resource represents a collaborative effort of the genetics community to establish an evidence-based resource for the assessment of the clinical relevance of genes and variants. This knowledge base is critical for confident, efficient analysis and interpretation of genome-scale sequence data. The objective is to provide a publicly available consensus summary of the evidence from the medical literature, basic science researchers, and clinical laboratories regarding the genes and variants that are implicated in human health and disease. Dedicated portals will be provided for researchers, clinical laboratories, physicians, patients, and electronic health records to ensure that the resource is widely accessible. The consortium of investigators will accomplish this objective by pursuing five specific aims: 1) developing a semi-quantitative methodology for assessing the "clinical actionability" of gene- phenotype pairs, which will allow stakeholder groups to provide guidance on the reporting and use of such genetic results; 2) establishing a standardized process for evaluating whether variants are benign, related to disease, or of uncertain significance; 3) deploying an informatics infrastructure to support the activities of the consortiu by aggregating information from disparate sources and presenting it for human evaluation; 4) assembling clinical domain-specific working groups to systematically evaluate the genes (and the variants in those genes) that are clinically relevant; and 5) ensuring the interoperability of he resource with electronic medical record systems. The approach innovates by developing novel approaches for the assessment of genes and variants that are robust and reproducible, and by establishing a distributed informatics system for aggregating and displaying information, with mechanisms for updating and reanalysis. The proposal is forward-thinking in that attention will be paid to ensuring the interoperability of the resource with diverse end-users, including electronic health records. The proposed resource project is significant because it will provide freely available expert curation of the human genome across a substantial number of clinical domains, with a transparent and evidence-based approach.