Braak co-expression modules.Genes were analyzed for co-expression across regions R1–R6 in the Allen Human Brain Atlas. a Module eigengene correlation with Braak stages. Each point reflects a module showing its correlation r with Braak stages (x-axis) and −log10-transformed P-values (BH-corrected; y-axis); 23 significant modules (BH-corrected P < 0.0001, t-test) were selected for further analysis (blue and red points). b Eigengene expression of all 167 modules across brain regions (rows) of donor 9861 sorted by their correlation with Braak stages (column colors). The vertical line separates negatively and positively correlated modules, and correlations are shown for two modules with the lowest and highest correlation. Brain regions involved in Braak includes the following anatomical structures: myelencephalon (MY), pontine tegmentum (PTg), substantia nigra (SN), CA2-field (CA2), basal nucleus of Meynert (nbM), amygdala (Amg), occipito-temporal gyrus (OTG), temporal lobe (TL), cingulate gyrus (CgG), parietal lobe (PL), and frontal lobe (FL). Modules were low expressed in the arcuate nucleus of medulla, locus coeruleus and CA2-field, independently of their correlation with Braak stages (Supplementary Fig. 7). c Significant modules were sorted based on their correlation with Braak stages (columns) and assessed for significant overlap with Braak stage-related genes (BRGs), cell-type markers, and gene sets associated with functional GO-terms or diseases (brown squares, BH-corrected P < 0.05, hypergeometric test). The number of genes within each module and tested gene set is given between brackets. Additionally, these modules revealed the presence of genes associated with Parkinson’s disease variants (annotated at the top) that have (blue and red) or have not (black) been identified as BRGs. A full version of this table showing all significant associations is given in Supplementary Fig. 10.
