PROJECT SUMMARY - BIOMARKER CORE The JHU Center for the Advancement of HIV Neurotherapeutics (JHU CAHN) will focus on a CNS complications that commonly present in PWH based on the framework of the NIMH Research Domain Criteria (RDoC) that classifies CNS complications based on dimensions of observable behavior and neurobiological measures that include Negative and Positive Valence Systems (e.g., anhedonia, fear), Sensorimotor Systems, Systems for Social Processes (e.g., social avoidance), Arousal/Regulatory Systems (e.g., sleep), and cognition. This framework provides new opportunities to more accurately associate biomarkers with particular symptomology with the goal of identifying molecular targets for the development of personalized medicine approaches by the Therapeutics and Clinical Cores. The Biomarker Core will work closely with the Therapeutic and Clinical cores to integrate multi-dimensional data and tools such as machine learning algorithms and offer these services to investigators interested in NeuroHIV. Technical services will include mass spectrometry analysis for metabolites, lipids, and proteins, multiplex Meso Scale discovery assays, extracellular vesicle isolation and cargo characterization. Informatics analyses offered will include Small Molecules Pathway Database, Kyoto Encyclopedia of Genes and Genomes, Cytoscape, and Ingenuity Pathway Analysis. Advanced non-parametric analyses will include a variety of multivariate modeling such as principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and sparse PLS-DA analysis, Significance analysis of metabolites (SAM), and Empirical Bayesian analysis of metabolites (EBAM) models to identify features that discriminate clinical biotypes or experimental groups. These services will be communicated broadly to the NeuroHIV community through our multicenter weekly seminar series. These services are unique to the JHU CAHN, and provide a valuable resource to NeuroHIV investigators at all stages of career development.