Human Phenotyping Core Project Summary This highly successful Human Phenotyping Core focuses on providing Center investigators with access to state-of-the-art technologies and methods for utilizing multi-parameter, high-content approaches to assess molecular phenotypes for rheumatic disease research. This Core coordinates expertise and core competencies in transcriptomics, proteomics, high-content cellular immunophenotypes, single-cell multiomics and tissue- based spatial multiomics. As such, it continues as a resource where ORDRCC Investigators can generate, share and analyze the multi-dimensional molecular phenotype data necessary for developing competitive research programs. Beyond giving ORDRCC investigators access to advanced technologies that are currently established at OMRF, this Core offers newly developed services providing access to data analytics in single- cell multi-omics from blood or dissociated tissue, as well as spatially aware tissue-based single-cell approaches. Our platforms enable investigators to define patient molecular profiles based on genetic, transcriptome, cellular, and/or proteomic differences in specific cell populations, as well as at the individual cell level with single cell 10X Genomics multiomic approaches, either 3’ or 5’ scRNA-seq/high-plex CITE-seq + BCR/TCR repertoire, or snRNA-seq/snATAC-seq for epigenetic analyses. Currently evolving approaches using fixed cells or fixed tissue dissociated to single cells on the Chromium X platform offer additional options for difficult to obtain cell populations from existing archival pathology samples in some cases. Spatial technologies have also advanced significantly and include multiomic (transcript and protein biomarkers) approaches. Capitalizing on the magnitude of information available through our carefully processed, well-organized, clinically characterized samples; our ability to provide comprehensive multi-analyte molecular phenotype profiles provide a foundational resource for identifying new research directions and generating new ideas for future collaborative projects. Aims of the updated Human Phenotyping Core are: AIM 1: Assist ORDRCC Investigators, JCIs and Scholars to navigate the stages of project development, experimental design, resource planning and execution of translational and mechanistic studies through Core Management and individual consultations, AIM 2: Provide access and training in use of molecular single-cell and spatial multiomic technologies using the technical personnel experienced in these advanced approaches, AIM 3: Establish data analytics pipelines for quality control, dataset generation and advanced modeling of single-cell and spatial multiomic data, and molecular phenotyping for patient stratification, AIM 4: Evaluate, assess and implement emerging technology and analytics approaches to more accurately assess patient heterogeneity in disease presentation and treatment responses. The HPC evaluates new technologies, working with the i...