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pmid:37904700
Identification of ferroptosis-related genes in type 2 diabetes mellitus based on machine learning.
Sen Wang · Yongpan Lu · Tingting Chi · Yixin Zhang · Yuli Zhao · Huimin Guo · Li Feng
Immunity, inflammation and disease · 2023 doi:10.1002/iid3.1036
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Experiment
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Complete file
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This study uses bioinformatics techniques identify new diagnostic T2DM biomarkers associated with ferroptosis.\nMETHODS: To identify ferroptosis-related genes (FRGs) that are differentially expressed between T2DM patients and healthy individuals, we first obtained T2DM sequencing data and FRGs from the Gene Expression Omnibus (GEO) database and FerrDb database. Then, drug-gene interaction networks and competitive endogenous RNA (ceRNA) networks linked to the marker genes were built after marker genes were filtered by two machine learning algorithms (LASSO and SVM-RFE algorithms). Finally, to confirm the expression of marker genes, the GSE76895 dataset was utilized. The protein and RNA expression of some marker genes in T2DM and nondiabetic tissues was also examined by Western blotting, immunohistochemistry (IHC), immunofluorescence (IF) and quantitative real-time PCR (qRT-PCR).\nRESULTS: We obtained 58 differentially expressed genes (DEGs) associated with ferroptosis. GO and KEGG enrichment analyses showed that these DEGs were significantly enriched in hypoxia and ferroptosis. Subsequently, eight marker genes (SCD, CD44, HIF1A, BCAT2, MTF1, HILPDA, NR1D2, and MYCN) were screened by LASSO and SVM-RFE machine learning algorithms, and a model was constructed based on these eight genes. This model also has high diagnostic power. In addition, based on these eight genes, we obtained 48 drugs and constructed a complex ceRNA network map. Finally, Western blotting, IHC, IF, and qRT-PCR results of clinical samples further confirmed the results of public databases.\nCONCLUSIONS: The diagnosis and aetiology of T2DM can be greatly aided by eight FRGs, providing novel therapeutic avenues.", "claims": [{"id": "claim-method", "statement": "We examined DEGs between T2DM samples and normal samples using the limma package in R software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37904700", "locator": "sections[4] \"Screening ferroptosis‐related differentially expressed genes (DEGs)\" paragraph 2", "quote": "We examined DEGs between T2DM samples and normal samples using the limma package in R software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available from the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37904700", "locator": "sections[40] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The data that support the findings of this study are available from the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "According to our ROC curve results, the eight marker gene‐based logistic regression model offered more sensitivity and precision than the independent marker genes for discriminating T2DM samples from normal samples, with an AUC of 0.832 (95% confidence interval [CI]: 0.760–0.896) (Figure 3G).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "According to our ROC curve results, the eight marker gene‐based logistic regression model offered more sensitivity and precision than the independent marker genes for discriminating T2DM samples from normal samples, with an AUC of 0.832 (95% confidence interval [CI]: 0.760–0.896) (Figure 3G)."}, "evidence": [{"asset": "source:pmid:37904700", "locator": "sections[21] \"Eight ferroptosis‐related DEGs were identified as diagnostic genes for T2DM\" paragraph 4", "quote": "According to our ROC curve results, the eight marker gene‐based logistic regression model offered more sensitivity and precision than the independent marker genes for discriminating T2DM samples from normal samples, with an AUC of 0.832 (95% confidence interval [CI]: 0.760–0.896) (Figure 3G)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "According to our ROC curve results, the eight marker gene‐based logistic regression model offered more sensitivity and precision than the independent marker genes for discriminating T2DM samples from normal samples, with an AUC of 0.832 (95% confidence interval [CI]: 0.760–0.896) (Figure 3G).", "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:37904700"], "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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