Computational systems immunology core

Abstract The three research projects of this program project grant utilize single cell genomic strategies and complementary imaging strategies to define cell-cell interactions in target tissues in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These projects will be used to develop insight into the development, function, localization, and interactions of B and T lymphocytes (Project 1), monocytes (Project 2), and fibroblasts (Project 3). Key to understanding these cell-types is the effective interpretation of complex high- dimensional data sets. The Computational Systems Immunology (CSI) core will support the analytical and computational needs for the three projects. This core will build from our experience with the Accelerating Medical Partnerships (AMP) RA/SLE program where analysis of high dimensional single cell data sets has now given us the first look at the constituent immune and stromal cellular populations. CSI will 1) employ computational strategies to analyze and integrate multiple single cell RNA-seq datasets to define key cellular populations 2) use trajectory analysis to define transitional states between cells. 3) Define clonal populations with repertoire sequencing and 4) Define the relationship between cell-cell interactions and transcriptional states. The CSI is uniquely positioned to analyze and integrate RA and SLE data with its long-standing expertise in rheumatic diseases, systems biology, and imaging analysis.