HMOX1 as a therapeutic target associated with diabetic foot ulcers based on single-cell analysis and machine learning.

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Although macrophages are associated with DFU, their exact role in this disease remains uncertain. This study sought to detect macrophage-related genes in DFU and identify possible therapeutic targets. Single-cell datasets (GSE223964) and RNA-seq datasets (GSM68183, GSE80178, GSE134431 and GSE147890) associated with DFU were retrieved from the gene expression omnibus (GEO) database for this study. Analysis of the provided single-cell data revealed the distribution of macrophage subpopulations in the DFU. Four independent RNA-seq datasets were merged into a single DFU cohort and further analysed using bioinformatics. This included differential expression (DEG) analysis, multiple machine learning algorithms to identify biomarkers and enrichment analysis. Finally, key results were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western bolt. Finally, the findings were validated using RT-qPCR and western blot. We obtained 802 macrophage-related genes in single-cell analysis. Differential expression analysis yielded 743 DEGs. Thirty-seven macrophage-associated DEGs were identified by cross-analysis of marker genes with macrophage-associated DEGs. Thirty-seven intersections were screened and cross-analysed using four machine learning algorithms. Finally, HMOX1 was identified as a potentially valuable biomarker. HMOX1 was significantly associated with biological pathways such as the insulin signalling pathway. The results showed that HMOX1 was significantly overexpressed in DFU samples. In conclusion, the analytical results of this study identified HMOX1 as a potentially valuable biomarker associated with macrophages in DFU. The results of our analysis improve our understanding of the mechanism of macrophage action in this disease and may be useful in developing targeted therapies for DFU.", "claims": [{"id": "claim-method", "statement": "The biomarker expression levels in samples from patients with DFU and samples from healthy individuals were compared using the independent t‐test, and the significance level was set at p < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38468410", "locator": "sections[6] \"Identification of potential biomarkers for DFU based on four machine algorithms\" paragraph 3", "quote": "The biomarker expression levels in samples from patients with DFU and samples from healthy individuals were compared using the independent t‐test, and the significance level was set at p < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data supporting the conclusions of this manuscript will be made available by the corresponding authors, without undue reservation, to any qualified researcher.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38468410", "locator": "sections[27] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The raw data supporting the conclusions of this manuscript will be made available by the corresponding authors, without undue reservation, to any qualified researcher."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified HMOX1 as a potentially valuable macrophage-associated biomarker for diabetic foot ulcers.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38468410", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In conclusion, the analytical results of this study identified HMOX1 as a potentially valuable biomarker associated with macrophages in DFU."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified HMOX1 as a potentially valuable macrophage-associated biomarker for diabetic foot ulcers.", "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:38468410"], "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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Finally, the findings wer", ". Finally, the findings were validated using RT-qPCR and western blot. We obtained 802 macrophage", "n-quantitative polymerase chain reaction (RT-qPCR) and Western bolt. Finally, the findings wer", "inally, the findings were validated using RT-qPCR and western blot. We obtained 802 macrophage"], "order_basis": "paper_text_order:1141", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["he findings were validated using RT-qPCR and western blot. We obtained 802 macrophage-related genes in", "This was consistent with the results of the Western blot analysis, which also indicated an increased"], "order_basis": "paper_text_order:1223", "id": "assay:2"}]}