CORE E PROJECT SUMMARY Recent advances in high-throughput immune phenotyping and genomic technologies have enabled profiling of host immune responses to vaccination and infection at unprecedented detail, at both the tissue and cellular level. The goal of the VIVA DATA MANAGEMENT AND ANALYSIS CORE (DMAC, CORE E) will be to provide comprehensive data management and computational analysis capabilities for the gene expression, antibody, cytokine and chemokine profiles generated for PBMCs and plasma from vaccinated and infected individuals, as well as from human tonsillar histocultures (HC) treated with different vaccines against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2; Project 1), influenza virus (IV; Project 2) or Dengue virus (DENV; Project 3). In Aim 1, this core will perform computational analysis of high-throughput tissue-level transcriptional, antibody, cytokine and chemokine profiles generated for all individuals and histocultures in each project by the IMMUNE PHENOTYPING CORE (CORE C) and the GENOMICS CORE (CORE D). In Aim 2, we will use the results from the analyses of bulk PBMC and plasma profiles – in close coordination with each project team – to help inform the selection of samples for detailed profiling at the cellular level using the latest single-cell CITEseq and spatial transcriptomics technologies by the GENOMICS CORE. We will also be responsible for analyzing the resulting single-cell datasets using well-established pipelines to show how changes in cell composition and expression at the cellular level drive changes at the tissue level. In Aim 3 we will further combine data at the tissue and cellular level across all three projects for an integrated analysis of host responses to vaccination against each pathogen to identify common and vaccine- specific components of these responses. This integration will be facilitated by the centralized cross-project data management facilities provided by this core, as well as coordinated data generation by the IMMUNE PHENOTYPING CORE and GENOMICS CORE that use the same platforms and technologies to profile samples across all projects. Finally, we will interface with ImmPort, directly or through the HIPC Coordinating Center, to ensure that all data, analysis results, and analysis code is made publically available in a timely manner. Altogether we expect that our multi-scale computational approaches will enable a comprehensive characterization of the relationship between vaccination, host immune responses and vaccine outcomes.