Fig. 2

Co-expression analysis in human and mouse reveals asymmetric transcriptome divergence, greatest in the human cerebral cortex. a Generation of module divergence scores. Plots showing preservation (Zsum) of co-expression modules (upper—human, lower—mouse) in a number of test expression datasets derived from human and mouse (red is human, blue is mouse). Black lines represent the upper quartile (UQ) of the Zsum scores. Module divergence is calculated by comparing the UQ of the human Zsum scores vs the mouse Zsum scores. The module divergence score is rounded up to zero in those cases where the module shows greater preservation in the opposing species. For each species, we have an example of a cortical derived module that shows species-specific divergence and one which does not. Error bars represent the 95% CI from permuting across study in that species. b Module divergence scores for all human and mouse-derived modules, each depicted as a single dot. Human modules show significant (*; p < 0.05) and over twice the average (black box) transcriptomic divergence than mouse suggesting that differences between human and mouse brain are mostly due to divergence on the human lineage. c Divergence scores for human- and mouse-derived modules stratified by region and ordered by regional: absolute divergence (average module divergence; upper) and relative divergence (divergence index score; the ratio of the average human- and mouse-module divergence scores for each region; lower). Black box represents mean regional divergence score. Amygdala (AMY) shows greatest absolute transcriptomic divergence with cortical regions showing greatest relative transcriptomic divergence. * denotes significant (p < 0.05) difference between the species for regional divergence scores. d Regional divergence (average module divergence for each region) plotted for both human and mouse. e Human brain regions plotted against their relative transcriptomic divergence (Divergence Index) with point size reflecting absolute transcriptome divergence. Human cortical regions show the greatest relative and the most significant transcriptomic divergence. Error bars represent the 95% CI from permuting across study in that species; * denotes regions with a CI that does not overlap zero