Identifying age-specific gene signatures of the human cerebral cortex with joint analysis of transcriptomes and functional connectomes

Abstract

The human cerebral cortex undergoes profound structural and functional dynamic variations across the lifespan, whereas the underlying molecular mechanisms remain unclear. Here, with a novel method transcriptome-connectome correlation analysis (TCA), which integrates the brain functional magnetic resonance images and region-specific transcriptomes, we identify age-specific cortex (ASC) gene signatures for adolescence, early adulthood and late adulthood. The ASC gene signatures are significantly correlated with the cortical thickness (P-value <2.00e-3) and myelination (P-value <1.00e-3), two key brain structural features that vary in accordance with brain development. In addition to the molecular underpinning of age-related brain functions, the ASC gene signatures allow delineation of the molecular mechanisms of neuropsychiatric disorders, such as the regulation between ARNT2 and its target gene ETF1 involved in Schizophrenia. We further validate the ASC gene signatures with published gene sets associated with the adult cortex, and confirm the robustness of TCA on other brain image datasets. Availability: All scripts are written in R. Scripts for the TCA method and related statistics result can be freely accessed at https://github.com/Soulnature/TCA. Additional data related to this paper may be requested from the authors.

Keywords: MRI; brain development; connectome; neuropsychiatric disorders; transcriptome.