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. 2023 Sep 11;15(9):e45063.
doi: 10.7759/cureus.45063. eCollection 2023 Sep.

Identifying Crucial Biomarkers in Osteoporosis and Ulcerative Colitis Through Bioinformatics Analysis of Co-expressed Genes

Zhengyan Wang  1 , Xukai Wang  1 , Jing Yan  2 , Ying Wang  1 , Xingxing Yu  1 , Yanpeng Wang  1
Affiliations

Identifying Crucial Biomarkers in Osteoporosis and Ulcerative Colitis Through Bioinformatics Analysis of Co-expressed Genes

Zhengyan Wang et al. Cureus. .

Abstract

Osteoporosis (OP) and ulcerative colitis (UC), prevalent immune diseases, exert a substantial socioeconomic impact globally. This study identifies biomarkers for these diseases, paving the way for in-depth research. Initially, the Gene Expression Omnibus (GEO) database was employed to analyze datasets GSE35958 and GSE87466. This analysis aimed to pinpoint co-expression differential genes (DEGs) between OP and UC. Subsequently, the Metascape database facilitated the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these DEGs' co-expression. For network construction and visualization, the STRING11.5 database along with Cytoscape 3.7.2 (Cytoscape Team, USA) were utilized to create a protein-protein interaction (PPI) network. Moreover, Cytoscape's cytoHubba plugin was instrumental in identifying the central genes, known as hub genes. In the datasets GSE35958 and GSE87466, 156 co-expressed DEGs were discovered. The PPI network, constructed using STRING11.5 and Cytoscape 3.7.2, comprises 96 nodes and 222 connections. Notably, seven hub genes were identified, namely COL6A1, COL6A2, BGN, NID1, PLAU, TGFB1, and PLAUR. These DEGs were predominantly enriched in pathways such as extracellular matrix organization and collagen-containing extracellular matrix, as per GO analysis. For diagnostic model construction and hub gene validation, datasets GSE56815 and GSE107499 from the GEO database were employed. The top five hub genes were validated. In conclusion, the hub genes identified in this study played a significant role in the early diagnosis, prevention, and treatment of OP and UC. Furthermore, they provide fresh insights into the underlying mechanisms of these diseases' development and progression.

Keywords: computational biology; differentially expressed genes (degs); gene expression omnibus (geo) database; osteoporosis (op); ulcerative colitis (uc).

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flow chart
GSEA: Gene Set Enrichment Analysis, OP: osteoporosis, UC: ulcerative colitis, KEGG: Kyoto Encyclopedia of Genes and Genomes, GO: Gene Ontology, PPI: protein-protein interaction
Figure 2
Figure 2. Screening the datasets for differentially expressed genes.
(A) A volcanic map of the differential genes identified in the GSE35958 (OP) dataset. (B) A volcanic map of the differential genes identified in the GSE87466 (UC) dataset. OP: osteoporosis, UC: ulcerative colitis
Figure 3
Figure 3. GO and KEGG analysis of the datasets.
(A) BP, (B) CC, (C) MF, and (D) KEGG of the GSE35958 (OP) dataset. (E) BP, (F) CC, (G) MF, and (H) (KEGG) of the GSE87466 (UC) dataset. BP: biological processes, CC: cellular components, MF: molecular function, KEGG: Kyoto Encyclopedia of Genes and Genomes, GO: Gene Ontology, OP: osteoporosis, UC: ulcerative colitis
Figure 4
Figure 4. GSEA analysis of the datasets
(A) GSEA of GSE35958 (OP) dataset. (B) GSEA of GSE87466 (UC) dataset. GSEA: Gene Set Enrichment Analysis, OP: osteoporosis, UC: ulcerative colitis
Figure 5
Figure 5. Screening and analyzing for co-expression differential genes
(A) Venn of GSE35958 (OP) and GSE87466 (UC). (B) BP of co-expression of differential genes. (C) CC of co-expression of differential genes. (D) MF of co-expression of differential genes. (E) KEGG of co-expression of differential genes. OP: osteoporosis, UC: ulcerative colitis, BP: biological processes, CC: cellular components, MF: molecular function, KEGG: Kyoto Encyclopedia of Genes and Genomes
Figure 6
Figure 6. PPI network of co-expression of differential genes.
Red is the upregulated gene. Green is the downregulated gene. PPI: protein-protein interaction
Figure 7
Figure 7. Hub genes based on four algorithms of Cytoscape 3.7.2 based on cytoHubba plugin.
(A) Degree algorithm, (B) DMNC algorithm, (C) MCC algorithm, (D) MNC algorithm.
Figure 8
Figure 8. Screening for core module
(A-D) The core module of Cytoscape 3.7.2 based on MCODE plugin.
Figure 9
Figure 9. Screening and analyzing for hub genes.
(A) Hub genes of Venn based on four algorithms of Cytoscape 3.7.2 based on cytoHubba plugin. (B) GO and KEGG of 7 Hub genes. KEGG: Kyoto Encyclopedia of Genes and Genomes, GO: Gene Ontology
Figure 10
Figure 10. ROC validation of GSE56815
Diagnostic model of (A) COL6A1, (B) COL6A2, (C) BGN, (D) NID1, (E) PLAU, and (F) general map based on GSE56815 (OP). ROC: Receiver Operating Characteristic, OP: osteoporosis
Figure 11
Figure 11. ROC validation of GSE107499
Diagnostic model of (A) COL6A1, (B) COL6A2, (C) BGN, (D) NID1, (E) PLAU, and (F) general map based on GSE107499 (UC). ROC: Receiver Operating Characteristic, UC: ulcerative colitis
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