Abstract The Analytic Core will process and harmonize multi-omics and multimodal endophenotype data, and provide advanced computational systems biology methods and frameworks for data integration and analysis for the entire project. Our multidisciplinary team has substantial expertise in multi-omics data analysis, data harmonization, computational method development, multi-omics data integration, genetic association analysis, neuroimaging analysis, data visualization, biostatistics, and network analysis. The Core will support collaborative work of the U19 project by providing processed multi-omics and multimodal phenotype data and enhancing the interoperability of analysis methods and pipelines. Furthermore, the Core will work closely with the Administrative Core to curate and share newly generated data and to provide documentation of data processing for public access. The overall goal of the U19 is to identify and validate centrally-linked longitudinal peripheral biomarkers of Alzheimer’s disease (AD) in multi-ethnic populations by integrating longitudinal multi-omics and multimodal phenotypes from eight independent cohorts. To achieve this goal, harmonized high-quality processed data and advanced computational and systems biology methods and pipelines for data analysis are critical to the entire project. First, the Analytic Core will provide high-quality and harmonized high-throughput multi-omics data from blood and brain tissue and multimodal neuroimaging, cognitive and postmortem neuropathology data. This data will permit analyses connecting peripheral and central changes within and across clinical, community-based and multi-ethnic cohorts and samples. The Core will also implement and provide advanced computational, systems biology frameworks for high-dimensional data analysis, enabling investigators from all three projects to perform data integration and analysis. To this end, the Analytic Core will be comprised of five teams: Omics, Imaging, Clinical, Neuropathology, and Computational and Systems Biology teams. The Analytic Core will focus on new data processing and integrative analysis framework development of longitudinal multi-omics data in relation to longitudinal multimodal endophenotypes. In Aim 1, we will assemble and provide state-of-the-art pipelines for processing high-dimensional multi-omics from blood and brain tissue and multimodal neuroimaging data, as well as clinical, cognition and neuropathology phenotypes for all projects. In Aim 2, we will implement and provide advanced multi-omics and multimodal endophenotype data integration and analysis approaches and pipelines for the entire project, which include but not limited to (1) novel systems biology and deep learning platforms for identification of blood molecular signatures that are associated with molecular signatures in the brain; (2) network-guided integrative analysis methods for multi-omics data integration to predict disease progression; and (3) an advanced system for ...