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）是一个综合数据导航平台，包含基因表达、大脑 来自多个物种的体外和体内神经元细胞的连接性、参考图谱和表征， 包括人、小鼠和非人灵长类动物。AD数据核心将在此基础上构建，以提供 针对来自AD Center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 Data Core还将与其他中心和用户组建立合作伙伴关系， 通过AD细胞表征项目产生的丰富数据的影响。 对单细胞进行详细分子和空间分析的新工具正在彻底改变我们的理解 但是新兴技术的力量还没有被应用于表征神经病理学， 阿尔茨海默病（AD）。该提案旨在通过使用转录组学、表观遗传学和 多重分子空间分析方法在细胞类型水平上表征AD病理学。集中 和管理的方法来收集，存储，处理，注释，分析和共享数据是必不可少的。 成功的整合将产生描绘AD的分子谱的基础数据集，并且AD数据 核心将通过一个具有催化作用的开放门户网站向社区提供结果。AD Data Core还将利用 主要的单细胞分析计划正在开发的方法，以利于AD研究。艾伦研究所 脑科学、NIH BRAIN Initiative Cell Census Network（BICCN）和人类细胞图谱（HCA）资助了 在细胞水平上表征非病理性大脑的补充努力，包括脑细胞数据 中心（BCDC），AD数据中心提案旨在与之协同。的专门知识和 该小组的许多成员已经开发出了建立BCDC所需的方法学工具 AD数据核心利用现有的、严格的协作努力为该过程提供了巨大的经济效益 为AD建立细胞分析能力的“手臂”。已制定的最佳做法， 最大限度地提高数据的可用性，现在可以带来广告研究与这个项目。协同这些细胞分析 通过利用来自其他细胞中心的内容，计划提供了加速AD研究进展的机会 数据库和相应的分析方法。拟议的AD数据核心也将是一个端到端 可以适应未来规模的平台，例如患者队列的增长、新的数据模式，以及 AD或相关认知障碍的其他临床方面。最后，AD核心将与临床 通过可访问的网络数据导航工具， 通过论坛、黑客马拉松和信息叙述等外联方式提供信息。

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.