Core C: Genomics and Transcriptomics

项目概要：核心C：基因组学和遗传学 核心C的主要目的是支持U54 FTD的基因组学和转录组学需求 中心没有墙。利用来自721名neu患者的现有全基因组测序数据， 本核心将提供基础信息， 关于tau代谢途径基因的变异，该中心将直接询问 通过其项目。中心提名的其他候选基因将由核心C筛选， 与人类神经退行性疾病的关系。同时，该核心将产生“tau多基因风险”， 将用于对tau介导的neu的高遗传风险与低遗传风险的样本进行分层的“TPRS”评分。 变性这些样本将由项目2进行研究，以阐明细胞过程， tau在具有不同程度的tau介导的神经变性遗传风险的患者中失调。 核心C还将在整个研究过程中支持项目的生物信息学和统计需求 期间，包括分析项目2产生的散装和单核转录组学数据。所有 这些数据将被整合到一个信息数据库中，即“Tau代谢和变异数据库” （TMVdb），与行政核心A协作。TMVdb将定期更新， 用于生成它的数据将通过分析提供给研究界， 工作台接口。核心的所有拟议活动将有助于实现中心的主要目标， 了解人类遗传变异如何有助于tau代谢和稳态， 这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.