Autism spectrum disorder (ASD) is genetically heterogeneous, with most ASD-associated variants accounting for very few cases. Michael Snyder and colleagues used a systems biology approach to identify common pathways dysregulated in ASD (Mol. Syst. Biol. 10, 774, 2014). Highly interacting modules were extracted from a protein interaction network. Two modules were significantly enriched for known ASD susceptibility genes, and one contained multiple genes involved in synaptic transmission. Whole-exome or whole-genome sequencing of 25 ASD and 5 control brains, followed by comparison to the 1000 Genomes Project database, identified 38 genes in this module that were significantly affected by rare, coding variants in individuals with ASD, 28 of which had not been previously linked to ASD. Expression analysis of all genes in the module found that they clustered into two groups, one preferentially expressed in the corpus callosum and the other more ubiquitously expressed. The corpus callosum is involved in communication between the brain hemispheres. The authors generated RNA sequencing data from the corpus callosum of six individuals with ASD and matched controls and found that the expression levels of genes in the module were significantly altered in ASD cases. This association did not hold for synaptic genes or ASD-associated genes in general.