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pmid:37215183
Exploring the common diagnostic gene KCNJ15 and shared pathway of ankylosing spondylitis and ulcerative colitis through integrated bioinformatics.
Su-Zhe Zhou · Li Shen · Zhong-Biao Fu · Hao Li · Ying-Lian Pan · Run-Ze Yu
Frontiers in physiology · 2023 doi:10.3389/fphys.2023.1146538
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Complete file
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But the common pathogenesis that explains the relationship between AS and UC is still lacked, and the related genetic research is limited. We purposed to explore shared biomarkers and pathways of AS and UC through integrated bioinformatics. Methods: Gene expression data of AS and UC were obtained in the GEO database. We applied weighted gene co-expression network analysis (WGCNA) to identify AS-related and UC-related co-expression gene modules. Subsequently, machine learning algorithm was used to further screen hub genes. We validated the expression level and diagnostic efficiency of the shared diagnostic gene of AS and UC in external datasets. Gene set enrichment analysis (GSEA) was applied to analyze pathway-level changes between disease group and normal group. Finally, we analyzed the relationship between hub biomarker and immune microenvironment by using the CIBERSORT deconvolution algorithm. Results: 203 genes were obtained by overlapping AS-related gene module and UC-related gene module. Through SVM-RFE algorithm, 19 hub diagnostic genes were selected for AS in GSE25101 and 6 hub diagnostic genes were selected for UC in GSE94648. KCNJ15 was obtained as a common diagnostic gene of AS and UC. The expression of KCNJ15 was validated in independent datasets, and the results showed that KCNJ15 were similarly upregulated in AS samples and UC samples. Besides, ROC analysis also revealed that KCNJ15 had good diagnostic efficacy. The GSEA analysis revealed that oxidative phosphorylation pathway was the shared pathway of AS and UC. In addition, CIBERSORT results revealed the correlation between KCNJ15 gene and immune microenvironment in AS and UC. Conclusion: We have explored a common diagnostic gene KCNJ15 and a shared oxidative phosphorylation pathway of AS and UC through integrated bioinformatics, which may provide a potential diagnostic biomarker and novel insight for studying the mechanism of AS-related UC.", "claims": [{"id": "claim-method", "statement": "We applied SVM-RFE to further select core diagnostic genes from the above intersected genes of the AS-related module and UC-related gene module by using the “e1071” R package (Yoon and Kim, 2009).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37215183", "locator": "sections[5] \"2.3 Identification and validation of diagnostic biomarkers\" paragraph 2", "quote": "We applied SVM-RFE to further select core diagnostic genes from the above intersected genes of the AS-related module and UC-related gene module by using the “e1071” R package (Yoon and Kim, 2009)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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The names of the repository/repositories and accession number(s) can be found in the article/supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "KCNJ15 was identified as a common diagnostic gene for ankylosing spondylitis and ulcerative colitis, with good diagnostic efficacy in the discovery and independent validation datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37215183", "locator": "sections[10] \"3.2 Identification of common diagnostic gene by machine learning algorithm\" paragraph 2", "quote": "Finally, KCNJ15 was identified as the common diagnostic gene of AS and UC (Figure 3C)."}, {"asset": "source:pmid:37215183", "locator": "sections[11] \"3.3 Validation of hub diagnostic genes\" paragraph 2", "quote": "In addition, the ROC analysis results showed that KCNJ15 had good diagnostic efficacy in GSE2510 (AUC = 0.723) and GSE94648 (AUC = 0.963) (Figures 4E, F)."}, {"asset": "source:pmid:37215183", "locator": "sections[11] \"3.3 Validation of hub diagnostic genes\" paragraph 2", "quote": "In the external independent datasets, KCNJ15 also showed potent diagnostic efficacy in GSE73754 (AUC = 0.757) and GSE38713 (AUC = 0.892) (Figures 4G, H)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "KCNJ15 was identified as a common diagnostic gene for ankylosing spondylitis and ulcerative colitis, with good diagnostic efficacy in the discovery and independent validation datasets.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37215183"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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