Integrated Transcriptomic Analysis Provided Diagnostic and Pathophysiological Insights for Epilepsy.

Area of Science:

• Genomics and Molecular Biology
• Neurology and Neuroscience
• Immunology

Background:

• Epilepsy is a complex neurological disorder with a multifactorial genetic and molecular basis.
• Identifying differentially expressed genes (DEGs) and hub genes is crucial for understanding epilepsy's pathophysiology.
• This knowledge can inform the development of improved diagnostic and therapeutic strategies for epilepsy.

Purpose of the Study:

• To identify key genes associated with epilepsy using transcriptomic and single-cell sequencing data.
• To develop a diagnostic model for epilepsy based on identified hub genes.
• To explore the functional roles of these genes in epilepsy pathogenesis, particularly concerning immune regulation.

Main Methods:

• Analysis of two epilepsy transcriptomic datasets (GSE143272, GSE32534) and one single-cell dataset (GSE201048) from the Gene Expression Omnibus (GEO) database.
• Differential gene expression analysis using the Limma R package.
• Identification and analysis of hub genes via STRING database and Cytoscape, followed by functional enrichment analysis using clusterProfiler R package.
• Construction and validation of an epilepsy diagnostic model using receiver operating characteristic (ROC) curves.

Main Results:

• Identification of multiple differentially expressed genes (DEGs) in epilepsy, with 20 common DEGs found across the two primary datasets.
• Eleven hub genes closely linked to epilepsy were identified through protein-protein interaction (PPI) network analysis.
• Four genes (CD3D, CD3G, CTSW, JCHAIN) exhibited consistent low expression in epilepsy samples across datasets.
• A diagnostic model utilizing these four genes demonstrated significant discriminatory ability (Area Under Curve > 0.7) in both epilepsy datasets.
• Functional and single-cell analyses indicated a strong association of these key genes with T cell function and immune regulation in epilepsy.

Conclusions:

• Four key genes (CD3D, CD3G, CTSW, JCHAIN) have been identified as significantly linked to epilepsy.
• These genes play a role in the immune regulation of epilepsy, potentially through T cell pathways.
• The identified genes contribute to the molecular diagnosis of epilepsy and offer insights into its underlying mechanisms.