Functional module-centric interpretation of transcriptomic change between human and chimpanzee cerebral cortex

Abstract

Characterizing the transcriptomic change between human and chimpanzee brains can provide clues for identifying the cellular functions underlying human's enhanced cognition and the increased vulnerability to the neurodegenerative and psychiatric disorders. Despite some successes, previous studies might have limited sensitivity to detect specific cellular functions since the focus has been only on the strong signals appeared by individual genes or pairs. To overcome these limitations, we carried out two functional module-centric transcriptome analyses. We evaluated the coordinated differential expression and the altered coexpression within the various types of functional modules. In our comparative assessment, the functional module-centric coexpression analysis identified the most extensive functional implications, in comparison to the conventional gene-centric and functional module-centric differential expression analyses. Through the functional module-centric coexpression analysis, we detected several human-specific modules associated with human-specific phenotypes related on neurobiological processes. In summary, our results suggest the rearrangement of transcriptional regulation over individual and multiple functional modules as a plausible basis of human brain specializations.