PROJECT SUMMARY (Data Core) This U19 Center propose to use human TG/DRG tissue and painful neuromas to generate large-scale multi- omics datasets for the discovery and characterization of functional genetic elements, epigenetic signatures, and molecular/cellular pathways that underlie human pain transduction, transmission, and processing. As one of the key components of the Center, the Data Core aims to act as a data center by building data infrastructure, providing data management, coordination, analysis, and sharing to the investigators within the Center and other centers in the community. The projects will generate nearly 4,000 datasets of clinical (pain scores, demographics), single-cell RNA-seq, single-cell ATAC-seq, SNP genotyping, spatial transcriptomics from MERFISH, and physiology for over 1,700 samples from 150 donors. The Data Core will first harmonize the datasets and store in centralized MySQL database with accessible web interface for other cores in the Center. Standard bioinformatics pipelines will be developed to process the raw data in a systematic manner, including cell type annotation and spatial location in each brain region. The Data Core will also support the research Projects on their customized analysis, including power analysis, differential expression and chromatin accessibility across different cell types, brain regions, and diagnosis. It will also reveal the genetic variants that are associated with various molecular features via xQTL analysis. Last, all these computed blocks and tools will be integrated into a comprehensive, cloud-based, interactive web portal – Pain Data Portal, providing a generally useful resource for generating biological hypotheses, discovering effective diagnosis biomarkers, and developing new treatments for pain. The Data Core will also ensure a timely data transfer and expertise sharing with the other U19 and U24 centers in the community.