Abstract

In Silico Identification of Hub Genes and Molecular Mechanisms in Temporal Lobe Epilepsy via Weighted Gene Co-expression Network Analysis

Authors: Mustafa Makav, Huseyin Avni Eroglu, Cemre Aydeger, Baris Kaban, Murat Kayabas and Turgut Dolanbay

DOI: http://dx.doi.org/10.71081/cvj/2026.080

Abstract
Introduction: Temporal lobe epilepsy (TLE) that is often resistant to medication is the most prevalent type of focal epilepsy in adults. This study aimed to identify the genetic networks and fundamental molecular mechanisms involved in the pathogenesis of TLE using in silico methods, thereby defining potential target genes (hub genes) for novel therapeutic approaches. Methods: The GSE6947 dataset, obtained from the NCBI Gene Expression Omnibus (GEO) database, was used in this study. Weighted Gene Co-expression Network Analysis (WGCNA) was performed on a total of 129 samples and 5000 genes using a systems biology approach. Biological processes were identified through Gene Ontology (GO) enrichment analysis. To detect central genes via the Protein-Protein Interaction (PPI) network, Cytoscape software and the Maximal Clique Centrality (MCC) algorithm were employed. Furthermore, hub gene candidates were validated through Module Membership (MM) analysis. Results: WGCNA identified 18 co-expression modules, among which the Pink Module was directly associated with synaptic transmission and neurotransmitter release and demonstrated the strongest correlation with epilepsy. Based on the MCC scores, DCTN1, UBE2E1, UBE2E2, KLC1, UBE2E3, NEDD4L, STAT3, GABARAPL1, CYCS, and DCTN3 were identified as the top 10 hub genes. In the MM analysis, UBE2E2, RAB6B, PPP3CB, and CYFIP2 exhibited the highest values. Conclusion: The results of the analysis indicate that synaptic dysfunction, neuroinflammation (STAT3), mitochondrial stress (CYCS), and axonal transport mechanisms (DCTN1, DCTN3, KLC1) play critical roles in the pathophysiology of TLE. These identified hub genes are strong candidates for understanding the molecular mechanisms of TLE and for developing novel biomarkers and therapeutic strategies.

Keywords: Epilepsy, Hub genes, Neuroinflammation, Temporal lobe epilepsy, Weighted Gene Co-expression Network Analysis