PROJECT SUMMARY/ABSTRACT –SYSTEMS BIOLOGY & BIOSTATISTICS CORE F The RUSTBELT CFAR Systems Biology & Biostatistics Core F provides support to a wide range of CFAR investigators by offering new multi-omic technologies, advanced biostatistics and computational analysis of “big data,” a stronger foundation in functional immunology studies, and a comprehensive ‘omic data management and training platform. The key mission of Core F is to provide systems biology approaches that allow for integration of different layers of host immune responses, from molecular triggers of immune responses to transcriptional signatures and interaction with resident microbiota. We will continue to support functional immunology studies that remain fundamental to HIV research. The Core assists investigators with research rigor and reproducibility through implementation of best practices for study design, analysis, and public sharing of results. In Aim 1 Core F will support genomics and microbiome research in HIV immunology and pathogenesis by providing users with a robust technological platform for transcriptional analysis by RNA-seq as well as deep sequencing in clinical and animal models of HIV infection. In Aim 2 Core F provides training and consultation in functional immunology as well as centralized access to state-of-the-art immunologic technologies, protocols, and training for the isolation, manipulation, culturing, and expansion of primary immune cells from blood and tissue, thereby supporting the RUSTBELT CFAR’s HIV transmission, gender research, cure, and pathogenesis translation objectives. In Aim 3 Core F facilitates all aspects of systems biology studies, by offering a centralized data acquisition, management, and reporting structure for all cohorts and ‘omics, using high-capacity assay and analysis workflows as well as publicly available ‘omic data to build publications and databases. Lastly, in Aim 4 This service function includes the collection and preparation of ‘omic and functional data for coordination and distribution to investigators, collecting associated de-identified patient annotations needed for analysis, and study publication. Core F Core F performs biostatistical correlate analysis to identify key drivers of protective immune responses, assist in designing validation strategies and writing manuscripts, and provide the metadata and data standardization pipelines for upload of results to public databases. By providing fundamental immune modeling support paired with multi-omic methodologies to identify key drivers or biomarkers of the host-virus interface in HIV, Core F will foster the complete systems biology approach necessary to support CFAR investigators in their translational research toward HIV cure, prevention, gender discrepancies, response to treatment, and the immunopathological landscape.