Deconvolution of Transcriptional Networks in Post-Traumatic Stress Disorder Uncovers Master Regulators Driving Innate Immune System Function

Scientific Reports
Abolfazl Doostparast Torshizi, Kai Wang

Abstract

Post-Traumatic Stress Disorder (PTSD) is a psychiatric disorder that develops in individuals experiencing a shocking incident, but the underlying disease susceptibility gene networks remain poorly understood. Breen et al. conducted a Weighted Gene Co-expression Network Analysis on PTSD, and identified a dysregulated innate immune module associated with PTSD development. To further identify the Master Regulators (MRs) driving the network function, here we deconvoluted the transcriptional networks on the same datasets using ARACNe (Algorithm for Reconstruction of Accurate Cellular Networks) followed by protein activity analysis. We successfully identified several MRs including SOX3, TNFAIP3, TRAFD1, POU3F3, STAT2, and PML that govern the expression of a large collection of genes. Transcription factor binding site enrichment analysis verified the binding of these MRs to their predicted targets. Notably, the sub-networks regulated by TNFAIP3, TRAFD1 and PML are involved in innate immune response, suggesting that these MRs may correlate with the innate immune module identified by Breen et al. These findings were replicated in an independent dataset generated on expression microarrays. In conclusion, our analysis corroborated previou...Continue Reading

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Citations

Jan 12, 2019·Frontiers in Psychiatry·Clara SnijdersBart P F Rutten
Oct 22, 2020·PeerJ·Wanwan CaiWuzhou Yuan
Nov 17, 2020·Trends in Neurosciences·Marlene Kanmogne, Robyn S Klein

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Datasets Mentioned

BETA
GSE45035
GSE64814

Methods Mentioned

BETA
RNA-seq

Software Mentioned

Analytic enrichment analysis ( aREA
VIPER ( Virtual Inference of Protein - activity by Enriched Re...
ARACNe
Gene Set Enrichment Analysis ( GSEA )
profiler analysis GSEA
WGCNA
Bioconductor
Enriched
Ensembl BioMart tool
JASPAR

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