Gene Variant Curation Core (GVCC)

项目总结/摘要 基因和变异管理核心（GVCC）是一个多机构的核心，将成为中心枢纽， 癫痫多平台变异预测（EpiMVP）研究基因和变异的决策 无墙中心（Center Without Walls，CWOW）核心将整合来自人口的基因序列数据 以及EpiMVP项目的功能读数，以开发EpiPred。EpiPred 将是一个癫痫特异性计算模型，它将预测一个变异体致病的可能性， 良性的核心利用了五所主要大学调查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、 加州旧金山弗朗西斯科和华盛顿大学。核心的广泛目标是首先策划和 选择基因和变异体用于EpiMVP项目1 - 3的研究。这些数据将从大的 来自我们在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和大型财团测序项目。其次，GVCC将使用预测工具，蛋白质 从项目1 - 3的结构建模和功能数据，以创建和优化EpiPred，癫痫特异性 计算模型，该模型将预测变体是致病性的或良性的可能性。最后，GVCC 将支持无缝数据共享所需的数据管理和网络资源， 在癫痫社区实施EpiPred。GVCC将与ClinGen策展人和我们的 行业合作伙伴测试EpiPred在癫痫工作组独立策划的变体上的准确性 分组，允许改进ClinGen用于治疗的算法和标准。最终我们 旨在将EpiMVP预测算法纳入ClinGen策展实践，并最终纳入ACMG 标准也是。此外，为了扩大EpiPred对患者，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版本EpiPred。

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.