ABSTRACT The Immunogenomics and Systems Biology Core (ISCB) at University of Michigan will support the data analytics, management, and disease translation to meet the goals of the entire AMP AIM Network. The ISCB will be based on our extensive experience in the development of genetics and systems biology approaches, working with a broad range of multi-omics data including genetic, epigenetic, single-cell and spatial-seq data, to increase our understanding of the factors that contribute to disease pathogenesis and heterogeneity. The premise of our approach is that integrating genetic information with other -omic data, collected through the AMP AIM Network, will facilitate and accelerate discovery of critical pathogenic mechanisms and help unravel the biologic processes contributing to disease heterogeneity. This approach will utilize advanced analytical approaches in causal mechanism inference, modeling and single cell and spatial genomics data integration. To achieve this we will i) deploy highly customized, scalable, and robust data processing capabilities and standardized pipelines for curation, processing, management, and sharing of multi-omics and integrated clinical datasets; ii) build comprehensive disease specific roadmaps, and define shared and unique molecular mechanisms of AMP AIM target diseases utilizing statistical genetics and genomics approaches; iii) identify, characterize, and refine biomarkers shaping disease heterogeneity and intervention response by integrating multi-omics and clinical data through statistical and computational modeling.