Gene Variant Curation Core (GVCC)

基因变异管理核心 (GVCC)

基本信息

批准号：
10670381
负责人：
Gemma Louise Carvill
金额：
$ 17.7万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10670381
关键词：
3-Dimensional Algorithms American Back Benign Biochemical Bioinformatics California Cells Classification ClinVar Communities Complex Computer Models Computer software Data Data Set Decision Making Epilepsy Family Genes Genetic Genomic approach Goals Health Personnel Human Industry Institution Internet Knowledge Maps Medical Genetics Michigan Mission Modeling Neurons Online Systems Pathogenicity Patients Population Population Database Prevalence Process Property Proteins Proteomics Reporting Research Personnel Rodent Roentgen Rays San Francisco Structural Models Structure Test Result Testing Trans-Omics for Precision Medicine Universities Variant Washington Work Zebrafish annotation system care providers clinical care cohort data management data sharing gene discovery genetic testing genetic variant genomic data in vitro Model in vivo industry partner machine learning model medical schools neurogenetics neuron development novel online resource prediction algorithm predictive modeling predictive tools protein structure skills statistical and machine learning tool variant of unknown significance working group

项目摘要

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.

项目概要/摘要基因和变异管理核心 (GVCC) 是一个多机构核心，将成为基因和变异管理核心通过癫痫多平台变异预测 (EpiMVP) 研究基因和变异的决策无墙中心（CWOW）的项目。核心将整合来自人群的基因序列数据和患者队列，以及用于开发 EpiPred 的 EpiMVP 项目的功能读数。肾上腺素预防药将是一个针对癫痫的计算模型，可以预测变异是否致病或良性。该核心利用了五所主要大学研究人员广泛且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、密歇根大学加州旧金山和华盛顿大学。核心的总体目标是首先策划和选择 EpiMVP 项目 1-3 中研究的基因和变体。该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，例如以及 ClinVar 和大型联盟测序项目。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，用于创建和优化 EpiPred（一种癫痫专用药物）预测变异致病或良性可能性的计算模型。最后，GVCC 将支持无缝数据共享和所需的数据管理和基于网络的资源 EpiPred 在癫痫社区的实施。 GVCC 将与 ClinGen 策展人和我们的合作行业合作伙伴测试 EpiPred 对癫痫工作组独立策划的变异的准确性分组，允许改进 ClinGen 用于管理的算法和标准。最终，我们旨在将 EpiMVP 预测算法纳入 ClinGen 管理实践中，并最终将 ACMG 纳入其中标准也是如此。此外，扩大 EpiPred 对患者、家庭、医疗保健提供者和研究人员将建立一个基于网络的 EpiPred 版本。