Machine learning and network pharmacology identify keloid biomarkers (AMPH, TNFRSF9) and therapeutic targets (IL6, HAS2) for aloe-derived quercetin.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41544047", "kind": "science-record", "revision": 3, "content_hash": "sha256:41b2e150b0fc186c775ebe001e4f9b78c141327f1d26819001e33b67df04077c", "created_at": "2026-11-01T20:31:30Z", "updated_at": "2026-11-01T22:15:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Machine learning and network pharmacology identify keloid biomarkers (AMPH, TNFRSF9) and therapeutic targets (IL6, HAS2) for aloe-derived quercetin.", "doi": "10.1371/journal.pone.0340960", "pmid": "41544047", "authors": ["Congli Jia", "Fu Yang", "Yingchun Li"], "journal": "PloS one", "year": 2026, "abstract": "OBJECTIVE: This study aimed to identify diagnostic biomarkers for keloid and explore potential therapeutic agents from traditional Chinese medicine (TCM) by integrating network pharmacology approaches. Specifically, we sought to uncover key molecular targets for Aloe vera and validate their roles in keloid pathogenesis.\nMETHODS: We integrated keloid transcriptome datasets (GSE218007 and GSE237752) by merging GEO data, and identifying differentially expressed genes (DEGs). Functional enrichment analysis (GO, GSEA) and machine learning approaches were applied to select diagnostic biomarkers. Candidate genes were validated via Receiver Operating Characteristic (ROC) curves in training and independent cohorts (GSE44270). PPI networks and Cytohubba algorithms identified hub genes, while TCMSP-screened compounds from Aloe vera were docked with targets using molecular docking.\nRESULTS: 91 Identified DEGs enriched in fibrosis-related pathways. Machine learning prioritized two diagnostic biomarkers: AMPH and TNFRSF9 (AUC > 0.85 in training/testing). PPI analysis revealed IL6 as a hub gene. Aloe vera-derived quercetin targeted HAS2 and IL6 (both P < 0.05 in validation), with molecular docking confirming stable binding (binding energy <-7 kcal/mol). IL6 emerged as both a key network hub and a therapeutic target, linking keloid and TCM mechanisms.\nCONCLUSION: AMPH and TNFRSF9 are promising diagnostic biomarkers for keloid, while quercetin from Aloe vera targets HAS2 and IL6, offering therapeutic potential. The dual role of IL6 underscores its centrality in keloid pathogenesis, connecting bioinformatics predictions with TCM pharmacology. This study provides a foundation for clinical prediction and targeted treatment strategies.", "claims": [{"id": "claim-method", "statement": "Differentially Expressed Genes were identified with the screening criteria as follows: Adjusted P-value (adj.P.Val) < 0.05, Absolute log2 fold change (|log2FC|) > 1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41544047", "locator": "sections[7] \"2.2.1. Identification of differentially expressed genes (DEGs).\" paragraph 2", "quote": "Differentially Expressed Genes were identified with the screening criteria as follows: Adjusted P-value (adj.P.Val) < 0.05, Absolute log2 fold change (|log2FC|) > 1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "These datasets were obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/) and are publicly available, no new patient data were generated for this study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41544047", "locator": "sections[4] \"2.1.1. Dataset acquisition and merging.\" paragraph 2", "quote": "These datasets were obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/) and are publicly available, no new patient data were generated for this study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "AMPH and TNFRSF9 are promising diagnostic biomarkers for keloid, while quercetin from Aloe vera targets HAS2 and IL6, offering therapeutic potential.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41544047", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "AMPH and TNFRSF9 are promising diagnostic biomarkers for keloid, while quercetin from Aloe vera targets HAS2 and IL6, offering therapeutic potential."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "AMPH and TNFRSF9 are promising diagnostic biomarkers for keloid, while quercetin from Aloe vera targets HAS2 and IL6, offering therapeutic potential.", "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:41544047"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE218007"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE218007"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41544047", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0340960", "sha256": 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and are publicly available, no new patient data were generated for this study.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "These datasets were obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/) and are publicly available, no new patient data were generated for this study.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM6732515", "GSM6732516", "GSM6732517", "GSM6732518", "GSM6732519", "GSM6732520", "GSM6732521", "GSM6732522", "GSM6732523", "GSM6732524", "GSM6732525", "GSM6732526", "GSM6732527", "GSM6732528", "GSM6732529", "GSM6732530", "GSM6732531", "GSM6732532", "GSM6732533", "GSM6732534", "GSM6732535", "GSM6732536", "GSM6732537", "GSM6732538", "GSM6732539", "GSM6732540", "GSM6732541", "GSM6732542", "GSM6732543"], "sample_count": 29, "group_sizes": null, "group_sizes_basis": null, "platform": "23126", "taxon": "Homo sapiens", "title": "Keloid 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