SUMMARY/ABSTRACT The Genomics Core will provide sample processing and next-generation sequencing for the BRI HIPC Center entitled “Systems immunology profiling of respiratory viral infections in vulnerable populations”. This core will serve both Research Projects, receiving samples from the Clinical Core, and sharing high quality ‘omics profiles with the Data Management and Analysis Core. The Genomics Core has two Specific Aims, In Specific Aim 1, the Genomics Core will process nasal, blood and sputum samples and then perform genome scale bulk RNA sequencing. In Specific Aim 2, the Genomics Core will perform single cell proteogenomic sequencing (Total-seq) of both global and antigen-specific populations to elucidate single cell transcriptomes, single cell immunophenotypes, and T cell receptor (TCR)/B cell receptor (BCR) clonotypes. For the global T cell analysis, the Genomics Core will utilize the 10X Chromium platform with 10X Single Cell Immune Profiling and BioLegend TotalSeq protocols for simultaneous single cell measurements of gene expression, cell surface antibody staining and TCR/BCR reconstruction. For rare autoantigen-specific populations where too few cells are available for use on the 10X system, the Genomics Core will utilize cell sorting on a flow cytometer into multi-well plates. In both cases, the Genomics Core will integrate transcriptomic and TCR/BCR clonotype measurements to link cells sharing ancestral relationships. The antigen-specific T cells to be examined is dependent on the project with Research Project 1 focused on allergen-specific T cells and Research Project 2 focused on citrullinated-antigen-specific T cells, implicated in the pathogenesis of rheumatoid arthritis. All transcriptomic data generated by the Genomics Core will be aligned to human and viral reference genomes and processed prior to transfer to the Data Management and Analysis Core for advanced analysis. The Genomics Core will work closely with each of the Project and Core Leads in the HIPC Center.