Gene Variant Curation Core (GVCC)

项目摘要/摘要 基因和变体修复核心(GVCC)是一个多机构的核心，将成为 癫痫多平台变异预测(EpiMVP)研究中基因和变异的决策 这个中心的项目没有墙(CWow)。核心将整合来自种群的遗传序列数据 和患者队列，以及EpiMVP项目的功能读数，以开发EpiPred。EpiPred 将是一种特定于癫痫的计算模型，它将预测一种变异是致病的或 良性的。该核心利用了五所主要大学研究人员的广泛和多方面的专业知识 包括西北大学、威尔·康奈尔医学院、密歇根大学、 加州大学、旧金山大学和华盛顿大学。该核心的广泛目标是首先策划和 选择EpiMVP项目1-3中的基因和变种进行研究。这些数据将从大量数据中进行整理 来自临床基因检测行业的行业合作伙伴的人口数据库和患者数据集 以及ClinVar和大型财团的测序项目。其次，GVCC将使用预测工具，蛋白质 来自项目1-3的结构建模和功能数据，以创建和优化专门针对癫痫的EpiPred 预测变异是致病的或良性的可能性的计算模型。最后，GVCC 将支持无缝数据共享所需的数据管理和基于Web的资源 EpiPred在癫痫社区的实施。GVCC将与Clingen策展人和我们的 行业合作伙伴在由癫痫工作组独立策划的变体上测试EpiPred的准确性 小组，允许改进算法和Clingen用于管理的标准。最终，我们 目的将EpiMVP预测算法结合到Clingen Curration实践中，并最终将ACMG 标准也是如此。此外，为了扩大EpiPred的可及性，患者、家庭、医疗保健提供者和 研究人员我们将建立一个基于网络的EpiPred版本。

PROJECT SUMMARY/ABSTRACT The Gene and Variant Curation Core (GVCC) is a multi-institutional core that will be the central hub for decision making for the genes and variants for study by the Epilepsy Multiplatform Variant Prediction (EpiMVP) projects in this Center Without Walls (CWOW). The core will integrate genetic sequence data from population and patient cohorts, as well as the functional readouts from the EpiMVP projects to develop EpiPred. EpiPred will be an epilepsy-specific computational model that will predict the likelihood of a variant being pathogenic or benign. The core capitalizes on the broad and multifaceted expertise of investigators at five major universities including Northwestern University, Weill Cornell Medical College, University of Michigan, University of California San Francisco and University of Washington. The broad objective of the core is to firstly curate and select genes and variants for study in projects 1-3 of the EpiMVP. This data will be collated from large population databases and patient datasets from our industry partners in the clinical genetic testing industry as well as ClinVar and large consortia sequencing projects. Secondly the GVCC will use prediction tools, protein structural modeling and functional data from projects 1-3 to create and optimize EpiPred, an epilepsy-specific computational model that will predict the likelihood of a variant being pathogenic or benign. Finally, the GVCC will support data management and web-based resources needed for seamless data sharing and implementation of EpiPred in the epilepsy community. The GVCC will work with ClinGen curators and our industry partners to test EpiPred accuracy on variants that are curated independently by the Epilepsy Working Group, allowing refinement of both the algorithm and the criteria used by ClinGen for curation. Eventually, we aim to incorporate the EpiMVP prediction algorithms into ClinGen curation practices, and ultimately the ACMG criteria as well. Moreover, to expand the accessibility of EpiPred for patients, families, healthcare providers and researchers we will establish a web-based version of EpiPred.