Multi-Omics Core

项目总结(APOE U19酷睿F：多OMICS酷睿) 这个多组学核心(核心F)旨在开发和应用最先进的蛋白质组学、代谢组学和 脂质组学技术研究APOE基因对阿尔茨海默病(AD)发病风险的作用机制 分子水平、细胞水平和致病水平。鉴于复杂和协同通路的功能障碍 有助于AD的异质性，识别临床相关的分子(DNA、RNA、蛋白质、代谢物 和脂类)对于预测、诊断、治疗和预防AD是必不可少的。因此，该核心寻求开发和应用 基于质谱仪(MS)的技术，结合转录组研究，以揭示蛋白质组学， 代谢和脂类的变化。组学评估将直接使用人体组织和 生物流体、人体有机物、小鼠和细胞模型，以及分离的细胞隔间和蛋白质 与AD的复合体以载脂蛋白E异构体依赖的方式连接。为了实现这一目标，我们组建了一个 强大的多学科团队，拥有成熟和知名的蛋白质组学(Peng)、代谢组学研究人员 (彭)和脂质组学(HAN)，都在研究神经退行性变方面拥有广泛的专业知识。核心将适用于 U19组件的最新蛋白质组学、代谢组学和脂质组学战略，特别是项目 2、3和4以及核心B、C、D、E和G；核心还将进一步推进这些技术，以解决 ApoE研究界在以下目标方面未得到满足的需求：(I)开发和应用纳米级，27- 基于Plex MS的载脂蛋白E相关蛋白质组、蛋白质修饰和蛋白质分析平台 相互作用组；(2)开发和应用非靶向和靶向代谢组学技术，评价 分析载脂蛋白E影响的代谢物的假发现率；(Iii)脂类组学的发展和应用 服务于apoE研究界的技术；以及(4)应用多种组学方法来界定 载脂蛋白E基因、性别和疾病状况的影响。总而言之，这个核心将开发和提供 基于MS的尖端多组学方法发现新的关键载脂蛋白E相关分子/ 衰老过程中的网络和AD发病机制在U19中的应用。

PROJECT SUMMARY (APOE U19 Core F: Multi-Omics Core) This Multi-Omics Core (Core F) aims to develop and apply state-of-the-art proteomics, metabolomics and lipidomics technologies to investigate the mechanisms of APOE genotype on Alzheimer’s disease (AD) risk at the molecular, cellular and pathogenic levels. Given the dysfunction of complex and synergistic pathways contributes to AD heterogeneity, identifying clinically relevant molecules (DNAs, RNAs, proteins, metabolites and lipids) is essential to predict, diagnose, treat, and prevent AD. As such, this Core seeks to develop and apply technologies based on mass spectrometry (MS), coupled with transcriptome studies, to uncover proteomic, metabolomic, and lipidomic changes. Omics assessments will be made directly using human tissues and biofluids, human organoids, mouse and cell models, as well as isolated cellular compartments and protein complexes linked to AD in an apoE isoform-dependent manner. To achieve this goal, we have assembled a strong multidisciplinary team with established and renowned investigators in proteomics (Peng), metabolomics (Peng) and lipidomics (Han), both having extensive expertise in studying neurodegeneration. The Core will apply the latest proteomics, metabolomics and lipidomics strategies across U19 components, specifically Projects 2, 3, and 4, and Cores B, C, D, E, and G; the Core will also further advance these technologies to address unmet needs of the apoE research community in the following aims: (i) develop and apply a nanoscale, 27- plex MS-based platform for analyzing apoE-related proteome, protein modifications and protein interactome; (ii) develop and apply untargeted and targeted metabolomics technologies with evaluation of false discovery rate for analyzing apoE-affected metabolome; (iii) develop and apply the lipidomics technologies to serve the apoE research community; and (iv) apply multi-omics approaches to define the effects by APOE genotype, sex, and disease status. In summary, this Core will develop and provide the cutting edge MS-based multi-omics approaches for discovering novel, crucial apoE-related molecules/ networks during aging and AD pathogenesis in this U19 application.