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 本申请是作为对NOT-RM-19-009的补充而提交的 授予U 54 NS 093793。 共同基金支持一些资源，可以显着提高基因和变异， 未诊断疾病网络模式生物筛选中心的研究优先级， 超越。为了方便使用这些资源，我们建议创建一个工具， 临床遗传学家和模式生物科学家。 MARRVEL（模式生物聚集资源稀有变异体勘探）创建了两个 几年前，因为个性化医疗的罕见变异分析所需的重要数据是 在互联网上传播到几十个不同的地方。为了提高效率和简化访问， 这些数据源，我们创建了一个网络工具，允许用户查询数十个数据源，包括 GTEx，并链接到IMPC，KOMP 2的显示门户。 在本提案中，我们的目标是开发MARRVEL第2版，以促进共同基金的使用 罕见疾病研究社区的手动和自动数据分析资源。这一目标将 通过整合KOMP 2（IMPC）和PHAROS数据并使用 聚合数据集，以开发用于诊断和动物实验的机器辅助基因和变体优先级排序。 模型生成 我们的目标与NIH共同基金的目标一致，以增加资源的效用，以更广泛地使用 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.