Core C: Genomics and Transcriptomics

项目摘要：核心C：基因组学和转录组学 核心C的主要目标是支持U54 FTD的基因组学和转录组学需求 没有墙的中心。利用现有的721例中性粒细胞白血病患者的全基因组测序数据 退行性疾病和健康的老年人对照，这一核心将提供基本信息 关于该中心将直接询问的tau代谢途径基因的变异 通过它的项目。由该中心提名的其他候选基因将由Core C进行筛选 与人类神经退行性疾病的相关性。同时，这一核心将产生“tau多基因风险”。 Score‘(TPR)，将用于对tau介导的neu-1基因风险高和低的样本进行分层。 杆状变性。项目2将对这些样本进行研究，以阐明细胞过程 在具有不同程度的tau介导的神经变性遗传风险的患者中，tau的表达异常。 核心C还将在整个研究期间支持项目的生物信息学和统计需求。 期间，包括对项目2生成的批量和单核转录数据的分析。所有 这一数据将纳入一个信息数据库，即“牛油代谢和变异数据库”。 (TMVdb)，与管理核心A合作。TMVdb将定期更新，它和 用于生成数据的数据将通过分析提供给研究界 工作台界面。核心中心的所有拟议活动都将有助于实现中心的主要目标 了解人类基因变异如何有助于tau新陈代谢和动态平衡 对它的成功至关重要。

PROJECT SUMMARY: CORE C: GENOMICS AND TRANSCRIPTOMICS The primary objective of Core C is to support the genomics and transcriptomics needs of the U54 FTD Center without Walls. Utilizing pre-existing whole genome sequencing data from 721 patients with neu- rodegenerative disease and healthy older adult controls, this Core will provide foundational information regarding variation in tau metabolism pathway genes that will be directly interrogated by the Center through its Projects. Additional gene candidates nominated by the Center will be screened by Core C for relevance to human neurodegenerative disease. In parallel, this Core will generate a `tau polygenic risk score' (TPRS) that will be used to stratify samples at high versus low genetic risk for tau-mediated neu- rodegeneration. These samples will be studied by Project 2 to elucidate the cellular processes by which tau is dysregulated in patients with varying degrees of genetic risk for tau-mediated neurodegeneration. Core C will also support the bioinformatics and statistical needs of the Projects throughout the study period, including analysis of bulk and single-nucleus transcriptomics data generated by Project 2. All of this data will be integrated into an informational database, the `Tau Metabolism and Variant database' (TMVdb), in collaboration with administrative Core A. The TMVdb will be regularly updated and both it and the data used to generate it will be made available to the research community through an analytical workbench interface. All of the Core's proposed activities will contribute to the Center's primary goal of understanding how human genetic variation contributes to tau metabolism and homeostasis and will be critical to its success.