Chronic Pain study with RNA-Seq, miRNA-Seq data on dbGaP (111 participants)

phs001158 — Human Dorsal Root Ganglion RNA Landscape Profiling for Neuropathic and    Chronic Pain

Bulk and spatial RNA sequencing were performed on human Dorsal Root Ganglia (DRGs), peripheral sensory nerves and nodose ganglia and relative gene abundances were calculated. Various analyses were performed: <ol> <li>Human DRG gene expression profiles were contrasted with a panel of gene expression profiles of relevant tissues in human and mouse (integrating, among other sources, datasets from ENCODE and GTex) in order to identify.</li> <ol> <li>DRG-enriched gene expression, co-expression modules of DRG-expressed genes, and key transcriptional regulators in humans.</li> <li>Contrasting the human and mouse DRG transcriptomes to identify DRG-enriched gene expression patterns that were conserved between human and mouse, identifying putative cell types of expression of these genes, and potential known drugs that might target the corresponding gene products.</li> <li>Characterization of non-coding RNA profile of human and mouse DRGs.</li> <li>Characterization of DRG-enriched alternative splicing and alternative transcription start site usage based transcript variants in humans and mouse, and the overlap between these two species.</li> <li>Contrasting of human DRG and GTex human tibial nerve samples to identify putative axonally transported mRNAs in sensory neurons.</li> </ol> <li>Human DRG and peripheral nerves transcriptomes from donors suffering from neuropathic and/or chronic pain were contrasted with controls to identify.</li> <ol> <li>Differentially expressed genes, pathways and regulators path play a potential role in neuronal plasticity, electrophysiological activity, immune signaling and response.</li> <li>Predictive models (Random Forests) were built to jointly predict the sex and pain state of samples based on information contained solely in autosomal gene expression profile.</li> <li>Gene co-expression modules were identified and gene set enrichment analysis performed.to identify sample - pathway associations, and to broadly characterize plasticity in human DRG cell types.</li></ol> <li> Spatial transcriptomics was performed on human DRGs and nodose ganglia to obtain near single-neuron resolution.</li><ol><li> We identified distinct clusters of human DRG sensory neurons.</li><li> We characterized the expression of different gene families (e.g., GPCRs, sodium channels, potassium channels, etc.).</li><li> We investigated differences between male and female neurons.</li></ol> </ol>