The Systems Biology Core C (SB Core C) serves this P01 Program to provide high-throughput pipelines from sample acquisition through quality control, library preparation, sequencing, and pre-processing of sequencing data sets. The main objective of the Core is to generate gene expression data sets for analyses to define the RHCMV/SIV vaccine response and programming by IL-15 for SIV vaccine protection in rhesus macaque (RM) vaccine cohorts of pre-clinical studies. Core C will conduct the following Specific Aims: 1) Perform next- generation sequencing assays of whole blood, tissue, and single cell samples received from Projects 1 and 2; 2) Conduct NanoString nCounter analyses on whole blood samples from Project 1 to assess baseline IL-15 expression and response, and to interrogate the whole blood predictive protective signature to inform study assignments; 3) Manage big datasets of next-gen sequencing data for quality assurance, analysis, public database disposition, publication, and Program access. The Core will prepare and/or sequence libraries generated from tissues for spatial transcriptomics, libraries generated from single cells in blood and tissues for single cell RNA-seq analysis, and whole immune tissues including whole blood, lymph node (LN), spleen, bone marrow (BM) and gut-associated lymphoid tissues (GALT) for bulk and single cell RNA-seq analysis, including CITEseq. The Core will provide consistent, high-quality functional genomics data that will be housed by a secure data management system. Data generated by the Core will undergo quality control, pre-processing, and normalized matrix generation prior to being delivered for bioinformatics analyses to support all aspects of the scientific program.