Fig. 6

uDEGs were analyzed for uniquely dysregulated GO processes from L3 PNs and L5 PNs in individuals with DS compared to CTR subjects. A. Significant GO processes using L3 uDEGs show relatively more neurotransmitter, ion and receptor (NIR) and RNA processes (arrows) compared to L5 uDEGs. B. L5 uDEGs show relatively more metabolism and activity processes (arrows) compared to L3 uDEGs. C. The specific GO process 0009220, pyramidine ribonucleotide biosynthetic process, was dysregulated in L3 uDEGs via ancestral plots [16], which indicates the overall dysregulation of RNA metabolism. D. L3 uDEGs indicated the specific GO: 0022904, respiratory electron transport chain, is specifically dysregulated as part of the oxidative processes dysregulated by genotype. E. GO:2000310 regulation of NMDA receptor activity was dysregulated in L5 layer specifically, with ancestral plots showing upstream dysregulation is both specific to L5 and genotype specific to DS PNs. F. GO:0042776, proton motive force-driven mitochondrial ATP synthesis, a metabolic pathway, was uniquely dysregulated in L5 uDEGs, with ancestral plots showing L5 and genotype dysregulation of metabolic pathways. (Key: yellow = L3 uDEG; orange = L3 layer specific; green = L5 uDEG; cyan = L5 layer specific and purple = genotype changes seen in L3 and L5; * indicates a pathway seen in multiple ancestral plots)