Integrative gene and isoform co-expression networks reveal regulatory rewiring in stress-related psychiatric disorders

Abstract

Isoform-specific expression patterns have been linked to stress-related psychiatric disorders such as major depressive disorder (MDD). To further explore their involvement, we constructed co-expression networks using total gene expression (TE) and isoform ratio (IR) data from affected (n = 210, 81% with depressive symptoms) and unaffected (n = 95) individuals. Networks were validated using advanced graph generation methods. Our analysis revealed distinct differences in network topology and structure. Shared hubs exhibited unique co-regulatory patterns in each network, with key master hubs in the affected network showing association with psychiatric disorders. Gene Ontology enrichment highlighted condition-specific biological processes linked to each network's master hubs. Notably, isoform-level data uncovered unique co-regulatory interactions and enrichments not observed at the gene level. This is the first study to show network-level differences of gene and isoform co-expression between affected and unaffected individuals of stress-related psychiatric disorders, emphasizing the importance of isoforms in understanding the molecular mechanisms of these conditions.

Related Papers

• → Classification of FABP isoforms and tissues based on quantitative evaluation of transcript levels of these isoforms in various rat tissues(2009)39 cited
• → Functional Roles of the α Isoforms of the Na,K‐ATPase(2003)98 cited
• → Relative expression of TAp73 and ΔNp73 isoforms(2012)32 cited
• → Tissue specific expression of Myosin IC Isoforms(2014)21 cited
• → Physiological Role of Na,K‐ATPase Isoforms(2004)