Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus

Varun Alur; Varshita Raju; Basavaraj Vastrad; Chanabasayya Vastrad; Satish Kavatagimath; Shivakumar Kotturshetti

doi:10.1177/11795514231155635

Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus

Clin Med Insights Endocrinol Diabetes. 2023 Feb 20:16:11795514231155635. doi: 10.1177/11795514231155635. eCollection 2023.

Authors

Varun Alur¹, Varshita Raju², Basavaraj Vastrad³, Chanabasayya Vastrad⁴, Satish Kavatagimath⁵, Shivakumar Kotturshetti⁴

Affiliations

¹ Department of Endocrinology, J.J.M Medical College, Davanagere, Karnataka, India.
² Department of Obstetrics and Gynecology, J.J.M Medical College, Davanagere, Karnataka, India.
³ Department of Pharmaceutical Chemistry, K.L.E. College of Pharmacy, Gadag, Karnataka, India.
⁴ Biostatistics and Bioinformatics, Chanabasava Nilaya, Dharwad, Karnataka, India.
⁵ Department of Pharmacognosy, K.L.E. College of Pharmacy, Belagavi, Karnataka, India.

Abstract

Background: Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder. The aim of the present investigation was to identify gene signature specific to T2DM.

Methods: The next generation sequencing (NGS) dataset GSE81608 was retrieved from the gene expression omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs) between T2DM and normal controls. Then, Gene Ontology (GO) and pathway enrichment analysis, protein-protein interaction (PPI) network, modules, miRNA (micro RNA)-hub gene regulatory network construction and TF (transcription factor)-hub gene regulatory network construction, and topological analysis were performed. Receiver operating characteristic curve (ROC) analysis was also performed to verify the prognostic value of hub genes.

Results: A total of 927 DEGs (461 were up regulated and 466 down regulated genes) were identified in T2DM. GO and REACTOME results showed that DEGs mainly enriched in protein metabolic process, establishment of localization, metabolism of proteins, and metabolism. The top centrality hub genes APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1 were screened out as the critical genes. ROC analysis provides prognostic value of hub genes.

Conclusion: The potential crucial genes, especially APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1, might be linked with risk of T2DM. Our study provided novel insights of T2DM into genetics, molecular pathogenesis, and novel therapeutic targets.

Keywords: Type 2 diabetes mellitus; bioinformatics analysis; differentially expressed genes; hub genes; pathway enrichment analysis.