Fig. 6: Pathways enriched in Braak pseudo-time trajectory analyses of IMC-snRNAseq matched vulnerable neuronal clusters.

a UMAP representation of clustered MTG-derived neuronal subpopulations from snRNAseq dataset. b Matched neuronal clusters from IMC (orange line below) and snRNAseq (green line above) experiments. Colours of the connecting lines identify neuronal types (excitatory, inhibitory, and unclassified neurons) to which clusters were assigned to (“assigned neuronal subtype”). Relative widths of the connecting lines describe their relative match scores (a measure of confidence in the correspondence between the direct transcriptomic and immunohistological cluster associations with wider lines corresponding to higher matching scores). Summary clinical disease (left) and Braak (right) pseudo-time trajectories for the Exc−L4−6−RORB−LCN15 and Exc−L5−RORB−LINC01202 clusters (black line in c,d with trajectory directions indicated by the red arrowhead). e Heatmap describing the relative expression of gene pathways enriched at successive stages (modules) of Braak pseudo-time for the Exc−L4−6−RORB−LCN15 (upper) and Exc−L5−RORB−LINC01202 (lower) clusters. Pathways enriched in modules corresponding to the successive consecutive Braak pseudo-time stages identified for Exc−L4−6−RORB−LCN15 (f) and Exc−L5−RORB − LINC01202 (g) cluster trajectory analyses. Only pathways with FDR < 0.05, odds ratio > 8 and overlapping genes ≥ 3 were analysed.