Core D: Integrated Computational Analysis Core

INTEGRATED COMPUTATIONAL ANALYSIS CORE: PROJECT SUMMARY/ABSTRACT To investigate how disease relevant changes, such as Alzheimer’s disease, are linked to specific risk factors (e.g., age-related changes, protein aggregates, vascular pathologies, etc.) to alter the spatial arrangement of cell types in the brain and their gene expression profiles, we need to build high-resolution maps of brain tissue at the cellular level in individuals with and without pathology. Building these maps requires proper characterization of the pathological features, as well as a reproducible workflow for data generation and imaging. To this end, the Integrated Computational Analysis Core will work closely with the Spatial Multiomics Core, the Biospecimen Core, and the four Projects on all aspects of imaging and genomics data analysis. This includes the following: 1) Primary analysis, comprising image registration, segmentation, and gene expression quantification, 2) Secondary analysis, comprising cross-sample registration and cell type assignment using multiplexed protein expression and genome-wide transcriptomics data, and 3) Tertiary analysis, involving the derivation of discrete measurable attributes summarizing key aspects of cell type, gene expression, and pathological composition and distribution in space. By scaling up and adapting existing workflows to address these data analysis needs, this Core is centrally involved in all analysis aims of each Project, as well as being engaged in continuous feedback with the Spatial Multiomics Core to optimize data generation workflows. An additional goal of this core is to integrate the raw and processed data, as well as the spatial attribute models, into a queryable, interactive portal called the Multidimensional Atlas of Aging and Pathology in the Brain (MAAP-Brain) visualizer. This publicly accessible portal, along with dissemination of workflows through the educational component of this overall U19 proposal, will provide the brain aging and AD scientific community with an interface to engage with the large-scale data generated by the Projects and other Cores. Ultimately, we aim for this dissemination effort to allow external researchers to generate or validate their own hypotheses about changes in cellular composition and arrangement associated with aging and human brain pathology.