Transcriptomic dysregulation across cerebral cortex in autism spectrum disorder Penn NaturePortfolio ASD Autisum CerebralCortex TranscriptomicDysregulation
By Tarun Sai LomteNov 7 2022Reviewed by Aimee Molineux A recent study in Nature demonstrated transcriptomic dysregulation in the cerebral cortex in autism spectrum disorder .
The regional consistency of these patterns was evaluated by separately computing differential expression in each cortical region. The regional effect-size changes were compared with the corresponding whole-cortex signature. ASD transcriptomic signatures were consistent across the 11 cortical areas, despite the considerable variations in the number of differentially expressed genes due to sample size differences.
Further, the authors noted that the typical transcriptional patterns that distinguish cortical regions were significantly attenuated in ASD, with some posterior areas having strong attenuation patterns. Next, the researchers categorized genes across all samples into modules using weighted gene correlation network analysis and identified 35 gene co-expression modules.
Contrastingly, the IsoformM37 module, upregulated in ASD, was enriched for common genetic risk variants for ASD and contained genes involved in protein folding and heat-shock proteins. In addition, there were 13 modules with regionally variable dysregulation patterns in ASD. However, none of these were enriched for known ASD genetic risk variants.
Furthermore, cell-type deconvolution was performed using bulk temporal and frontal methylation profiling data from single-cell methylome analyses. The CTD analyses showed nominal increases and decreases in pre-frontal cortex microglia and temporal lobe oligodendrocytes, respectively, in ASD; nevertheless, these cell proportion shifts were not sustained after false-discovery rate correction.
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