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. 2023 Feb 20:16:11795514231155635.
doi: 10.1177/11795514231155635. eCollection 2023.

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

Varun Alur  1 , Varshita Raju  2 , Basavaraj Vastrad  3 , Chanabasayya Vastrad  4 , Satish Kavatagimath  5 , Shivakumar Kotturshetti  4
Affiliations

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

Varun Alur et al. Clin Med Insights Endocrinol Diabetes. .

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.

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Conflict of interest statement

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Research design flow chart.
Figure 2.
Figure 2.
Heat map of differentially expressed genes. Legend on the top left indicate log fold change of genes. (A1-A651 = normal control samples; B1-B949 = T2DM samples).
Figure 3.
Figure 3.
Volcano plot of differentially expressed genes. Genes with a significant change of more than two-fold were selected. Green dot represented up regulated significant genes and red dot represented down regulated significant genes.
Figure 4.
Figure 4.
PPI network of DEGs. The PPI network of DEGs was constructed using Cytoscap. Up regulated genes are marked in green; down regulated genes are marked in red. Big node represents nod with more number of interactions and small node represents nod with least number of interactions.
Figure 5.
Figure 5.
Modules of isolated form PPI of DEGs: (A) the most significant module was obtained from PPI network with 98 nodes and 117 edges for up regulated genes and (B) the most significant module was obtained from PPI network with 81 nodes and 248 edges for down regulated genes. Up regulated genes are marked in green; down regulated genes are marked in red.
Figure 6.
Figure 6.
MiRNA-hub gene regulatory network. The purple color diamond nodes represent the key miRNAs; up regulated genes are marked in green; down regulated genes are marked in orange.
Figure 7.
Figure 7.
TF-hub gene regulatory network. The blue color triangle nodes represent the key TFs; up regulated genes are marked in green; down regulated genes are marked in red.
Figure 8.
Figure 8.
ROC curve validated the sensitivity, specificity of hub genes as a predictive biomarker for T2DM: (A) APP, (B) MYH9, (C) TCTN2, (D) USP7, (E) SYNPO, (F) GRB2, (G) HSP90AB1, (H) UBC, (I) HSPA5, and (J) SQSTM1.
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References

    1. Caruso R, Magon A, Baroni I, et al.. Health literacy in type 2 diabetes patients: a systematic review of systematic reviews. Acta Diabetol. 2018;55:1-12. - PubMed
    1. Gruss SM, Nhim K, Gregg E, Bell M, Luman E, Albright A. Public health approaches to Type 2 diabetes prevention: the US National Diabetes Prevention Program and Beyond. Curr Diab Rep. 2019;19:78. - PMC - PubMed
    1. Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of type 2 diabetes - global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10:107-111. - PMC - PubMed
    1. Magliano DJ, Sacre JW, Harding JL, Gregg EW, Zimmet PZ, Shaw JE. Young-onset type 2 diabetes mellitus - implications for morbidity and mortality. Nat Rev Endocrinol. 2020;16:321-331. - PubMed
    1. Borzouei S, Soltanian AR. Application of an artificial neural network model for diagnosing type 2 diabetes mellitus and determining the relative importance of risk factors. Epidemiol Health. 2018;40:e2018007. - PMC - PubMed