Fig. 4: Brain networks exhibit transcriptional genome-wide and mitochondrial specialization.

a The Allen Mouse Brain Atlas gene expression data was used to identify OVER-expressed and UNDER-expressed biological processes among Network 1 areas compared to Networks 2 + 3 areas combined. The number of genes whose Network 1 expression are more than double (Log2 fold difference > 1) or less than half (Log2 fold difference <) relative to Networks 2 + 3 is listed in the tables (right). The top three corresponding enriched categories of biological pathways for Network 1 are listed in the tables; enriched categories for Networks 2 and 3 are available in Supplementary Fig. 13, and the gene lists are available in Supplementary File 2. b Principal component analysis (PCA) representation of gene expression signatures based on mitochondrial localized genes alone (n = 946) and c the expression of 149 mitochondrial pathways by brain area (MitoCarta3.0¹⁶), representing the relative expression of pathways relative to all brain areas. Analyses are performed on 16 areas because gene expression for dorsal and ventral DG is combined in the reference dataset. d Mitochondrial pathway scores ranked by their differential expression among networks 1 vs. 2 + 3. e, g Raw scores for selected divergent mitochondrial pathways illustrating the specialization of mitochondrial phenotypes (mitotypes) between brain areas, color coded by network. f, h Computed ratios of the two pathways analyzed in e and g, quantifying the magnitude of molecular specialization between brain areas in percentage of gene expression between the two juxtaposed ratios. Ratios are derived from scaled in situ RNA hybridization data so may not represent absolute differences in transcript abundance. Source data are provided as a Source Data file.