A Knowledge Base for Clinically Relevant Genes and Variants

描述(申请人提供)：基因测序技术的基本进步是由人类基因组计划推动的，现在反过来正在改变基因组科学和医学。然而，由于缺乏关于基因对疾病的贡献的权威信息来源，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，但如果它们继续断开联系，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，以建立一个基于证据的资源，用于评估基因和变异的临床相关性。这一知识库对于自信、高效地分析和解释基因组规模的序列数据至关重要。其目的是提供一份公开可用的共识摘要，总结来自医学文献、基础科学研究人员和临床实验室的证据，这些证据涉及与人类健康和疾病有关的基因和变异。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，以确保资源可广泛访问。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群体就此类基因结果的报告和使用提供指导；2)建立一个标准化的程序来评估变异是良性的、与疾病有关的还是具有不确定意义的；3)部署一个信息基础设施，通过从不同来源收集信息并将其提交给人类评估来支持该联盟的活动；4)组建针对临床领域的工作组，系统地评估与临床相关的基因(以及这些基因中的变体)；(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，用于评估健壮和可重复的基因和变异，并建立了一个分布式信息学系统，用于收集和显示信息，并具有更新和重新分析的机制。该提案具有前瞻性，因为将注意确保该资源与包括电子健康记录在内的不同最终用户的互操作性。拟议的资源项目意义重大，因为它将以透明和循证的方法，为大量临床领域的人类基因组提供免费的专家管理。

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.