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pmid:39418100
A lactate metabolism-related gene signature to diagnose osteoarthritis based on machine learning combined with experimental validation.
Jianhua Yang · Wenjun Li · Xuemei Lin · Wei Liang
Aging · 2024 doi:10.18632/aging.205873
Paper
complete
Experiment
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Data
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Analysis
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Execution
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Complete file
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This study aims to clarify the diagnosis value of lactate metabolism-related genes in osteoarthritis (OA).\nMETHODS: Lactate metabolism-related genes were retrieved from the MSigDB. GSE51588 was downloaded from the Gene Expression Omnibus (GEO) as the training dataset. GSE114007, GSE117999, and GSE82107 datasets were adopted for external validation. Genomic difference detection, protein-protein interaction network analysis, LASSO, SVM-RFE, Boruta, and univariate logistic regression (LR) analyses were used for feature selection. Multivariate LR, Random Forest (RF), Support Vector Machine (SVM), and XGBoost (XGB) were used to develop the multiple-gene diagnosis models. 12 control and 12 OA samples were collected from the local hospital for re-verification. The transfection assays were conducted to explore the regulatory ability of the gene to the apoptosis and vitality of chondrocytes.\nRESULTS: Through the bioinformatical analyses and machine learning algorithms, SLC2A1 and NDUFB9 of the 273 lactate metabolism-related genes were identified as the significant diagnosis biomarkers. The LR, RF, SVM, and XGB models performed impressively in the cohorts (AUC > 0.7). The local clinical samples indicated that SLC2A1 and NDUFB9 were both down-regulated in the OA samples (both P < 0.05). The knockdown of NDUFB9 inhibited the viability and promoted the apoptosis of the CHON-001 cells treated with IL-1beta (both P < 0.05).\nCONCLUSIONS: A lactate metabolism-related gene signature was constructed to diagnose OA, which was validated in multiple independent cohorts, local clinical samples, and cellular functional experiments.", "claims": [{"id": "claim-method", "statement": "Multivariate LR, Random Forest (RF), Support Vector Machine (SVM), and XGBoost (XGB) were used to develop the multiple-gene diagnosis models.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39418100", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Multivariate LR, Random Forest (RF), Support Vector Machine (SVM), and XGBoost (XGB) were used to develop the multiple-gene diagnosis models."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are openly available in GEO (https://www.ncbi.nlm.nih.gov/geo/) and MSigDB (https://www.gsea-msigdb.org/gsea/msigdb/index.jsp). 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The transfection assays were conducted to explore the regulat", "lated in the OA samples (both P < 0.05). The knockdown of NDUFB9 inhibited the viability and promot", "previously described [22, 23]. The transient transfection assays in the CHON-001 cells were conducted", "T-qPCR) experiments were used to measure the knockdown efficacy of the siRNAs. Supplementary Materi"], "order_basis": "paper_text_order:1024", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["re the regulatory ability of the gene to the apoptosis and vitality of chondrocytes. 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