Fig. 1: Transcriptome patterns in PD caudate and putamen.

a Overview of the study. Bulk RNA sequencing was performed in postmortem caudate and putamen from controls and PD patients. Antemortem blood transcriptome data was obtained from an independent cohort of subjects enrolled in the PPMI study. Clinical information was extracted from accompanying charts (postmortem donors) and open-access database (PPMI subjects) to determine molecular profiles associated with PD clinical variables. Parts of the image were created with BioRender.com. b Principal component analysis (PCA) shows the separation of caudate and putamen regions of striatum along PC1 (p value: 2.6 × 10⁻²⁰, Kruskal–Wallis test). Healthy controls and PD are separated along PC2 (p value: 2.08 × 10⁻⁸). Ellipses indicate confidence interval = 0.8 of indicated groups. c Volcano plot shows significantly changed RNAs in PD caudate and putamen compared to their respective controls. RNAs with significant changes in expression (determined by moderated t-tests with multiple test corrections using limma) with false discovery rate (FDR) <0.05 and an absolute value of log₂ fold change (FC, PD/Control) >0.1, 0.5, and 1 are colored according to direction. d Bubble plot shows representative top significantly (FDR <0.05) up- (log₂FC >0) and down (log₂FC <0) -regulated GO terms in both caudate and putamen, as determined by GSVA. SNARE: Soluble N-ethylmaleimide-sensitive factor attachment proteins receptor, GMP guanosine monophosphate, NOD nucleotide-binding oligomerization domain. e Sample-wise gene set enrichment scores (determined by GSVA) for individual donors show select GO terms that are changed in both regions. C- Controls (n = 40), PD (n = 35). f Gene set enrichment scores for individual donors show select GO terms that are preferentially changed in either caudate or putamen. C- Controls (n = 40), PD (n = 35). g Heatmap shows expression (log₂(counts per million), scaled by genes) of classifier genes (identified in caudate) in control and PD striatum. Significance for box plots were determined by the two-sided Wilcoxon test. Box plots show lower and upper hinges corresponding to the first and third quartiles (representing 25th and 75th percentile, respectively). Whiskers extend from the hinge to the 1.5 × inter-quartile range. The Center line indicates the median. Source data are provided as a Source Data file.