PROJECT SUMMARY/ABSTRACT – Genomic Technology Core The latest, cutting-edge genomic technologies including bulk and single-cell profiling of the transcriptome (e.g. RNA-seq), epigenome (e.g. ATAC-seq) and proteome (e.g. CITE-seq), represent powerful new tools for the advancement of precision medicine research, particularly when used to analyze biospecimens from well clinically-phenotyped individuals. These rapidly evolving technologies, with their requirements for specialized sample preparation and storage, genomic expertise and informatics skills, present a challenge for many clinical and translational researchers in rheumatology, a field where the need for better molecular characterization and improved delineation of disease subtypes is also a tremendous need. The goal of the Genomic Technology (GT) Core is to provide autoimmune rheumatic disease investigators turn-key solutions to cutting-edge genomic assays. To achieve this goal, we propose the following Aims: 1) Develop novel genomic assays and tailor them for direct application to the investigation of rheumatic disease patients. The GT Core will leverage the innovative expertise of the Ye Lab to develop multimodal, single-cell sequencing assays, high-throughput single cell proteomic assays, and spatial single-cell transcriptomic approaches. 2) Provide genomic consultation services and at-scale services for bulk and single-cell sequencing assays. The GT Core will draw on the collaborative genomic resource lab, the Genomics CoLab (Led by co-director Dr. Eckalbar), to develop workflows and analytic pathways geared toward the study of autoimmune disease that can be used by rheumatic disease investigators following consultation on genomic assay choice and study design, enabling them to implement cutting-edge genomic technologies for their projects. 3) Integrate and oversee the centralized biospecimen collection, storage and project tracking systems that are available, to ensure optimal use of patient samples and the integration and sharing of data between projects. The GT Core will continue to monitor the rigor and reproducibility of complex experimental pathways to also ensure the quality of the experimental data. The GT Core will closely collaborate with the Clinical Data Informatics (CDI) cores, to develop project specific sample tracking and metdata storage systems through Research Electronic Data Capture (REDCap) to ensure appropriate linkage of clinical data with biospecimen results. The GT Core will work closely with the IB Core to ensure that genomic data streams can be easily integrated into analysis workflows. The GT Core provides a robust framework for the application of novel, cutting-edge genomic technologies and will enable rheumatology investigators to maximally utilize all the tools available for the advancement of precision medicine research in rheumatology.