PT  - JOURNAL ARTICLE
AU  - Michael V. Lombardo
AU  - Eric Courchesne
AU  - Tiziano Pramparo
TI  - Hierarchical cortical transcriptome disorganization in autism
AID  - 10.1101/042937
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 042937
4099  - http://biorxiv.org/content/early/2016/03/10/042937.short
4100  - http://biorxiv.org/content/early/2016/03/10/042937.full
AB  - Elucidating how the cortical transcriptome is hierarchically disorganized may be key for understanding the pathophysiology behind of autism (ASD). Here we find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD. ASD-upregulated modules are primarily enriched in immune, inflammation, and translation processes. ASD-downregulated modules are primarily enriched in synaptic, cell adhesion, and cytoskeleton processes. These dysregulated modules are strongly correlated and form emergent properties characterized by the coordination of downregulated synaptic and neural developmental processes and upregulated catabolism, viral processes, translation, protein targeting and localization, interferon signaling, glia-relevant, and apoptosis processes. Organization at the level of clusters of highly connected modules (i.e. meta-modules) is also disrupted in ASD as is connectivity between specific synaptic, immune, and translation modules. These results support that transcriptome disorganization in ASD occurs at hierarchical levels to form emergent pathophysiology that is not readily apparent by studying smaller elements in isolation.