Fig. 5: Structural similarity and transcriptional co-expression networks.

a, Gene co-expression networks (upper triangles) compared to MIND networks and MSNs (lower triangles). LH, left hemisphere. b,c, Correlation between the gene similarity network and the group MSN or MIND network, at the level of edges (b) and weighted nodal degrees (c). Shading represents 95% confidence interval (CI) of best-fit line. P values (uncorrected) were based on a two-sided spin test that generated a distribution of null correlations from random spatial network rotations (Methods). d, Stability of the correlation between structural and transcriptomic networks constructed from all subsets of the six postmortem brain gene expression datasets available. Also included are results on univariate MIND networks derived from cortical thickness and consensus DTI connectivity from the HCP-YA dataset³⁹. For each number of donors included, all combinations of transcriptional networks were constructed (without gene filtering), and the mean edge correlation was calculated for each network type. There were \(\begin{array}{l}\left(\begin{array}{l}6 \\ n \end{array}\right)\end{array}\) possible networks created for n = 1, 2…6 included donors. Shading indicates the minimum and maximum value of the association observed for each number of included donors. e, Cortical brain maps of MIND weighted node degree beside a weighted gene expression map derived from PLS analysis of the covariation between degree, or ‘hubness’, of MIND nodes and gene expression. PLS1 explained a significant amount of covariance (62%, P_spin = 0.01, two-sided spin test) between these two modalities. f, Cell type enrichment of the weighted, ranked gene list from PLS analysis of covariation between MIND degree and gene expression, using the median loading rank within one of seven sets of genes, each characteristic of a canonical class of cells in the central nervous system: excitatory neurons (Neuro-Ex, P = 0.049), inhibitory neurons (Neuro-In, P = 0.17), endothelial cells (Endo, P = 0.81), astrocytes (Astro, P = 0.48), microglia (Micro, P = 0.02), oligodendrocytes (Oligo, P = 0.42) and oligodendroglial precursor cells (OPC, P = 0.30). The zero position on the x axis represents the median position of all 15,633 genes (position 7,816), with negative ranks indicating genes that have expression positively correlated with MIND node degree—that is, overexpressed at highly connected MIND network hubs. P values were FDR corrected after a two-sided permutation test controlling for both spatial autocorrelation in the brain MRI data and correlation structure in gene expression (*P < 0.05; see Methods for details).