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Rehawi, G. ; Hagenberg, J. ; Sämann, P.G.* ; Moyon, L. ; Binder, E.* ; List, M.* ; Marsico, A. ; Knauer-Arloth, J.

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

iScience 28:113342 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genetics ; Molecular Biology ; Neuroscience ; Omics; Molecular Networks; R-package; Expression; Transcriptome; Consequences; Mechanisms; Depression; Modules; Systems; Immune
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Zeitschrift iScience
Quellenangaben Band: 28, Heft: 9, Seiten: , Artikelnummer: 113342 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen Helmholtz Helmholtz Association under the joint research school "Munich School for Data Science-MUDS
Brain & Behavior Research Foundation (NARSAD Young Investigator )
BMBF Cluster4Future program CNATM
Klaus Tschira Stiftung (KTS, Klaus Tschira Foundation)