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

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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.