A data resource for high resolution neuropathological and omics analysis of Alzheimer's disease

摘要(数据核心) 艾伦研究所通过创建数据框架来支持 为研究界传播生物数据和分析工具。艾伦大脑图谱数据门户 (http://www.brain-map.org)是一个全面的数据导航平台，包含基因表达、大脑 来自多个物种的体外和体内神经细胞的连接性、参考图谱和特征， 包括人类、老鼠和非人类灵长类动物。AD数据核心将在此基础上构建，以提供 针对AD中心派生的大规模数据集的集中式数据集成和呈现解决方案 财团。AD数据核心还将与其他中心和用户组建立合作伙伴关系，以最大限度地提高 通过AD单元表征项目生成的丰富数据的影响。 对单细胞进行详细的分子和空间分析的新工具正在彻底改变我们的理解 但新兴技术的力量尚未被应用于表征脑部的神经病理学 阿尔茨海默病(AD)。这项提议旨在通过使用转录、表观遗传和 多重分子空间分析方法在细胞类型水平上表征AD病理。一个集中化的 而收集、存储、处理、注释、分析和共享数据的受管方法是必不可少的。 成功的整合将产生描述AD分子轮廓的基础数据集，以及AD数据 CORE将通过一个具有催化作用的开放门户网站向社区提供成果。AD数据核心还将利用 由主要的单细胞图谱倡议开发的方法，以利于AD研究。艾伦研究所 脑科学、NIH脑倡议细胞普查网络(BICCN)和人类细胞图谱(HCA)已获得资助 在细胞水平上描述非病理性大脑的互补努力，包括脑细胞数据 中心(BCDC)，AD数据中心计划旨在与该中心协同工作。专业知识和 建立BCDC所需的方法学工具已由小组的许多成员开发，并提议 用于AD数据核心。利用现有的、严谨的协作工作为流程提供了极大的经济性 为AD构建一个细胞特征分析能力的“手臂”。已为以下方面开发的最佳实践 通过此项目，现在可以将最大限度地提高数据可用性带到AD研究中。与这些细胞图谱的协同作用 计划提供了通过利用来自其他cell-centirc的内容来加快AD研究进展的机会 数据库和相应的分析方法。拟议的AD数据核心也将是端到端的 可适应未来规模的平台，例如患者群的增长、新的数据模式和 阿尔茨海默病或相关认知障碍的其他临床维度。最后，AD核心将与临床接洽 和研究社区通过可访问的基于网络的工具进行数据导航和传播 通过论坛、黑客松和信息叙述等外展方式提供信息。

ABSTRACT (DATA CORE) The Allen Institute has demonstrated a tradition of excellence by creating data frameworks to support the dissemination of biological data and analysis tools for the research community. The Allen Brain Atlas data portal (http://www.brain-map.org) is a comprehensive data navigation platform, containing gene expression, brain connectivity, reference atlases and characterization of in vitro and in vivo neuronal cells from multiple species, including human, mouse and non-human primate. The AD Data Core will build on this foundation, to provide centralized data integration and presentation solutions for large-scale data sets derived from the AD Center consortium. The AD Data Core will also form partnerships with other centers and user groups, to maximize impact of the rich data being generated through the AD cell characterization projects. New tools for detailed molecular and spatial analysis of single cells are revolutionizing our understanding of the brain, but the power of emerging techniques has not yet been applied to characterize neuropathology in Alzheimer’s disease (AD). This proposal aims to address this gap by using transcriptomic, epigenetic and multiplex molecular spatial analysis methods to characterize AD pathology at the level of cell types. A centralized and managed approach to collecting, storing, processing, annotating, analyzing and sharing the data is essential. Successful integration will yield a foundational data set depicting a molecular profile of AD, and the AD Data Core will serve results to the community via a catalytic open web portal. The AD Data Core will also leverage methods being developed by major single cell profiling initiatives, to benefit AD research. The Allen Institute for Brain Science, NIH BRAIN Initiative Cell Census Network (BICCN) and the Human Cell Atlas (HCA) have funded complementary efforts to characterize nonpathological brain at the cellular level, including a Brain Cell Data Center (BCDC), which the AD Data Center proposal is designed to synergize with. The expertise and methodological tools required to build the BCDC have been developed by many members of the team proposed for the AD Data Core. Utilization of an existing, rigorous collaborative effort offers great economy to the process of building out an “arm” of cellular profiling capability for AD. Best practices that have been developed for maximizing data usability can now be brought to AD research with this project. Synergy with these cell profiling initiatives offers opportunity to accelerate AD research progress by leveraging content from other cell-centirc databases and corresponding analysis methods. The proposed AD Data Core will also be an end-to-end platform that can accommodate future scale, such as growth of patient cohorts, new data modalities, and additional clinical dimensions of AD or related cognitive disorders. Finally, the AD Core will engage with clinical and research communities through accessible web-based tools for data navigation, and dissemination of information through outreach approaches such as forums, hackathons and informational narratives.