RT Journal Article
SR Electronic
T1 Hierarchical cortical transcriptome disorganization in autism
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 042937
DO 10.1101/042937
A1 Michael V. Lombardo
A1 Eric Courchesne
A1 Tiziano Pramparo
YR 2016
UL http://biorxiv.org/content/early/2016/03/15/042937.abstract
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 across 2 datasets for 10 gene co-expression modules that are differentially expressed in ASD. These modules span multiple cell types and compartments including M1 and M2 microglia, astrocytes, ribosomal subunits, neuron, synapse, and postsynaptic density. These dysregulated modules are also strongly correlated and form higher-level emergent properties characterized by coordination between downregulated synaptic and neural developmental processes and upregulated catabolism, viral processes, translation, protein targeting and localization, interferon signaling, glia-relevant, and apoptosis processes. Hierarchical 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 a view of hierarchical cortical transcriptome disorganization in ASD characterized by emergent pathophysiology not readily apparent in smaller isolated elements.