Core 1: Genomics and Data Management Core

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PROJECT SUMMARY Single cell RNA-seq and other transformative genomic technologies provide the opportunity to take human immunology to the next level of cellular detail, defining individual cells in greater orders of magnitude than previously possible. As a disease of great cellular heterogeneity, Systemic Lupus Erythematosus is ripe to be impacted by single cell technologies. The Genomics and Data Management Core (GDMC) will provide state- of-the-art genomics technologies and all data management capabilities for the proposed Center for Lupus Research. A major contribution of the GDMC will be to provide and develop the technology to analyze SLE patient samples with single cell resolution. Applying single cell technologies will help to define cell type characteristics in these patient populations, allow for specific comparisons between patient versus normal cell types and could potentially define new cell types associated with SLE and/or molecular subtypes of disease. Single cell RNA-seq will be used as a discovery tool to define cell populations and identify cell-type-specific markers. The flow and mass cytometry applications will utilize this information to develop new panels of antibodies that can be applied with greater throughput than single cell transcriptomics (i.e. on more patients and with greater numbers of cells per sample). Ultimately, the development of such a cellular phenotyping approach will enable improved stratification of SLE patients. In addition, the GDMC aims to provide the single cell tools to functionally interrogate new cell populations and pathways revealed by the resolving power of single cell transcriptomics, thus potentially uncovering new strategies for SLE therapeutics. The data management activities of the GDMC will ensure a unified and robust approach to experimental design and analysis for both research projects of the Center. GDMC will be responsible for the flow of data and information across all components of the Center and will be responsible for the submission of completed data sets/projects to the appropriate public archives. The Specific Aims for the GDMC are to 1) Provide state-of-the-art single cell transcriptomic technologies; 2) Provide state-of-the-art cellular phenotyping; and 3) Provide central storage, management and information security for data generated by the Center for Lupus Research. The core will thus fulfill essential scientific and translational needs across the Center through the application of powerful genomic technologies combined with expert data analysis and management support.