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pmid:38414629
Bioinformatics Analysis and Experimental Validation of Mitochondrial Autophagy Genes in Knee Osteoarthritis.
Kuihan Tang · Li Sun · Long Chen · Xiaobo Feng · Jiarui Wu · Hao Guo · Yong Zheng
International journal of general medicine · 2024 doi:10.2147/IJGM.S444847
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Experiment
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Complete file
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Differentially expressed mitochondrial autophagy gene (DEMGs) were screened in patients with KOA by differential expression analysis. The STRING website was used to construct a protein-protein interaction (PPI) network among DEMGs. Molecular complex detection (MCODE) method in Cytoscape software was performed to identify hub DEMGs. Support vector machine recursive feature elimination (SVM-RFE) method was used to construct the hub DEMG diagnosis model. Genes with diagnostic value were identified as biomarkers by plotting receiver operating characteristic (ROC) curves and Expression validation. CIBERSORT algorithm was used to calculate the proportion of 22 immune cells in each sample in the GSE114007 dataset. Finally, biomarker expression was verified by qPCR.\nResults: A total of 15 DEMGs were obtained and enrichment analyses showed that these DEMG strains were mainly enriched in the mitophagy-animal, shigellosis, autophagy-animal and FoxO signal pathways. The PPI network unveiled 13 DEMGs with interactions. In addition, 8 hub DEMGs (ULK1, CALCOCO2, MAP1LC3B, BNIP3L, GABARAPL1, BNIP3, FKBP8 and FOXO3) were obtained for KOA. And 5 model DEMGs (BNIP3L, BNIP3, MAP1LC3B, ULK1 and FOXO3) were screened. The ROC curves revealed that BNIP3 and FOXO3 has strong diagnostic value in these models of DEMG. Immune-infiltration and correlation analysis showed that BNIP3 and FOXO3 were significantly correlated with three different immune cells, including primary B cells, M0 macrophage and M2 macrophage. The cartilage tissue samples qPCR verification results show that FOXO3 and BNIP3 were all down-regulated in KOA (p < 0.01), and the validation results are consistent with the above analysis.\nConclusion: BNIP3 and FOXO3 have been identified as biomarkers for the diagnosis of KOA, which might supply a new insight for the pathogenesis and treatment of KOA.", "claims": [{"id": "claim-method", "statement": "In the GSE114007 dataset, differentially expressed genes (DEGs) between KOA samples and normal samples were detected utilizing the “DESeq2” R package (version 1.34.0) with an adjusted p<0.05 and a |log2FC|>0.5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38414629", "locator": "sections[4] \"Differential Expression Analysis\" paragraph 2", "quote": "In the GSE114007 dataset, differentially expressed genes (DEGs) between KOA samples and normal samples were detected utilizing the “DESeq2” R package (version 1.34.0) with an adjusted p<0.05 and a |log2FC|>0.5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE114007, GSE169077 and GSE51588 datasets analyzed in this study were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38414629", "locator": "sections[21] \"Data Sharing Statement\" paragraph 2", "quote": "The GSE114007, GSE169077 and GSE51588 datasets analyzed in this study were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 4279 DEGs, including 1969 down-regulated and 2310 up-regulated in KOA samples, were identified (Figure 1a and b).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38414629", "locator": "sections[11] \"Identification of DEMGs\" paragraph 2", "quote": "A total of 4279 DEGs, including 1969 down-regulated and 2310 up-regulated in KOA samples, were identified (Figure 1a and b)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 4279 DEGs, including 1969 down-regulated and 2310 up-regulated in KOA samples, were identified (Figure 1a and b).", "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:38414629"], "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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