In silico Molecular Insights into Canine Type ۱ Diabetes: Hub Genes and Druggable Candidates

Background: Diabetes mellitus is a common disease in dogs, and the most prevalent form resembles type ۱ diabetes (T۱D) in humans. Although extensive studies have been conducted, the molecular mechanisms underlying T۱D remain incompletely understood. This study aimed to explore gene expression changes in canine T۱D and to identify hub genes and potential therapeutic targets. Methods: Expression profiling data (GSE۱۴۸۸۷) were obtained from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using a p-value < ۰.۰۵ and Bonferroni correction. The protein–protein interaction network and molecular function (gene ontology) enrichment were constructed through STRING and analyzed in Cytoscape. Hub genes were systematically identified through network topology analysis using key parameters such as node degree, betweenness centrality, and neighborhood connectivity. Results: A total of ۱۱ DEGs were identified, including ۳ upregulated and ۸ downregulated genes. GO enrichment indicated significant involvement in lysozyme activity, cysteine-type endopeptidase and peptidase activity, Actin monomer binding, and nerve growth factor receptor binding. Network analysis highlighted CTSS, CTSD, and CTSH as hub genes with the highest degree and betweenness centrality, suggesting their pivotal role in T۱D pathogenesis. Functional enrichment revealed that these genes were mainly associated with cysteine-type endopeptidase activity and related proteolytic processes. Further analysis using Drug–Gene Interaction Database (DGIdb) indicated that these genes may be druggable, highlighting their potential as therapeutic targets. Conclusion: This study provides novel insights into the molecular mechanisms of canine T۱D. The identified hub genes not only expand our understanding of disease progression but also offer potential biomarkers and candidate targets for diagnosis and therapy in both veterinary and comparative medicine.

کلیدواژه ها:

Canine type ۱ diabetes ، Cathepsin ، Differentially expressed genes ، PPI