Fig. 1: Transcriptomic changes in the DLPFC from donors with OUD.

A, B Volcano plot of RNA-seq data shows DEGs (red) from OUD1 versus unaffected control donors (A) and OUD2 versus control donors (B). The horizontal dashed line represents the FDR significance cut-off (<0.1), and the dashed vertical lines represent a Log2FC cut-off ± 0.32 (FC = 1.25). C Venn diagram representing the overlap of DEGs in OUD1, OUD2, and OUD groups shows 56 shared DEGs across all group comparisons. D Correlation analysis of the fold change of combined DEGs from OUD1, (orange) OUD2 (blue). DEGs shared between OUD1 and OUD2 are shown in yellow. E RRHO analysis shows concordance of gene expression between OUD1 and OUD2 versus control in the DLPFC. Pixels represent overlap between the genome-wide transcriptome of each comparison, with the significance of overlap color-coded. The bottom left quadrant includes co-up-regulated genes, and the top right quadrant includes co-down-regulated genes compared to the control. Bottom right and top left quadrants include oppositely regulated genes. F Top: Hypergeometric analysis quantifying the enrichment of immediate early genes (IEGs) within the list of DEGs in OUD (red), OUD1 (orange) OUD2 (blue) groups. The X-axis represents −log₁₀(P-value); the size of the circle represents the number of overlapping genes. Bottom: heatmap represents the Log2FC of the 25 IEGs expressed in the DLPFC samples across OUD1, OUD2, and OUD groups. G Top Gene Ontology (GO) terms shared between OUD1 (orange) and OUD2 (blue) groups. The x-axis represents the odds ratio and measures effect size, and the size of the circle represents the −log₁₀(P-value). H Top 20 canonical pathways commonly enriched in the OUD1 and OUD2 groups. Pathways were clustered into four distinct groups based on the similarity of overlapping genes.