Common Fund Data Supplement: Integration of KOMP2 (IMPC) and PHAROS into MARRVEL 2.0 for machine learning-assisted rare variant prioritization

项目摘要 本申请是对NOT-RM-19-009的响应，作为家长的补充 获奖U54NS093793。 共同基金支持一些资源，这些资源可以显著增强基因和变体 在未诊断疾病网络的模式生物筛查中心进行优先研究 更远一点。为了方便使用这些资源，我们建议创建一个可通过以下方式轻松访问的工具 临床遗传学家和模型生物学家都是如此。 MARRVEL(稀有变异探索的模式生物聚合资源)创建了两个 因为对个性化药物进行罕见的变异分析所必需的重要数据是 在互联网上数十个不同的地点传播。要提高效率并简化访问 针对这些数据源，我们创建了一个Web工具，允许用户一次查询数十个数据源，包括 GTEx，并链接到KOMP2的显示门户IMPC。 在这项提案中，我们的目标是开发MARRVEL版本2，以促进共同基金的使用 用于手动和自动数据分析的罕见病研究社区的资源。这个目标将是 通过集成KOMP2(IMPC)和Pharos数据并使用 聚合数据集以开发用于诊断和动物的机器辅助基因和变体优先顺序 模型生成。 我们的目标与NIH共同基金的目标一致，以提高资源的效用，供更广泛的使用 在生物医学界。

Project Summary This application is being submitted in response to NOT-RM-19-009 as a supplement to the parent award U54NS093793. The Common Fund supports a number of resources that can significantly enhance gene and variant prioritization for study in the Model Organisms Screening Center of the Undiagnosed Diseases Network and beyond. To facilitate the use of these resources, we propose to create a tool that can be easily accessed by clinical geneticists and model organism scientists alike. MARRVEL (Model organism Aggregated Resources for Rare Variant ExpLoration) was created two years ago because important data that is necessary for rare variant analysis for personalized medicine is spread throughout the internet in tens of different locations. To improve efficiency and streamline access to these data sources, we created a web-tool that allows users to query tens of data sources at once, including GTEx, and links to IMPC, the display portal for KOMP2. In this proposal, our goal is to develop version 2 of MARRVEL to promote the use of Common Fund resources in the rare disease research community for manual and automated data analysis. This goal will be accomplished by developing MARRVEL 2.0 by integrating KOMP2 (IMPC) and PHAROS data and using the aggregated dataset to develop a machine-assisted gene and variant prioritization for diagnosis and animal model generation. Our goals align with those of the NIH Common Fund to increase the utility of resources for broader use in the biomedical community.