Co-expression Network Analysis of the Developing Human Brain Implicates Synaptogenesis and Mitochondrial Function as Central Mechanisms in Autism

Abstract

We analyzed the spatial-temporal co-expression relationships of 455 genes previously implicated in Autism spectrum disorder (ASD) using the BrainSpan transcriptome atlas. Understanding how the heterogenous set of ASD-related genes contribute to normal brain development helps identifying cellular/molecular processes which are commonly disrupted in ASD. First, we discovered modules among ASD candidates with biologically relevant temporal co-expression dynamics. These modules were related to the processes of synaptogenesis, apoptosis, and the neurotransmitter y-aminobutyric acid (GABA). Second, we created a transcriptome-wide co-expression network to discover significant Molecular Interaction Modules, and demonstrated that ASD candidate genes are enriched in modules related to the processes of synaptogenesis, mitochondrial function, protein translation, and ubiquitination. Finally, we identified hub genes within the ASD-enriched Molecular Interaction Modules, which may serve as additional ASD candidate genes, potential biomarkers, or therapeutic targets