Integrated Analysis of Brain Transcriptome Reveals Convergent Molecular Pathways in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders with etiology that remains elusive. Although there is a mounting body of investigation in different brain regions related to ASD, our knowledge about the common and distinct perturb condition between them is at the threshold of accumulation. In this study, based on protein-protein interactions, post-mortem transcriptome analysis was performed with corpus callosum (CC) and prefrontal cortex (PFC) samples from ASD individuals and controls. Co-expression network analysis revealed that a total of seven (four for CC set, three for PFC set) core dysfunctional modules strongly enriched for known ASD-risk genes. Three quarters of them in CC set (M4, M6, M29) significantly enriched for genes annotated by genetically associated variants in our previous whole genome sequencing data. We further determined transcriptional and post-transcriptional regulation subnetwork for each ASD-correlated module, including 47 pivot transcription factors, 130 pivot miRNAs, and 7 pivot lncRNAs. Moreover, there were significantly more interactions between CC-M4, -M6, and PFC-M2, mainly involved in synaptic functions and neuronal development. Our integrated multifactor analysis of ASD brain transcriptome profile illustrated underlying common and distinct molecular mechanisms and the module crosstalk between CC and PFC, helping to shed light on the molecular neuropathological underlying ASD.