Identification and validation of interferon-stimulated gene 15 as a biomarker for dermatomyositis by integrated bioinformatics analysis and machine learning.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39559355", "kind": "science-record", "revision": 4, "content_hash": "sha256:1b81ea832efaf93926445b5e9bd0d5a2aeecf0738d2d468deffb89dc41f9a144", "created_at": "2026-11-01T20:29:49Z", "updated_at": "2026-11-01T22:55:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of interferon-stimulated gene 15 as a biomarker for dermatomyositis by integrated bioinformatics analysis and machine learning.", "doi": "10.3389/fimmu.2024.1429817", "pmid": "39559355", "authors": ["Xingwang Wang", "Hao Hu", "Guangning Yan", "Bo Zheng", "Jinxia Luo", "Jianyong Fan"], "journal": "Frontiers in immunology", "year": 2024, "abstract": "Background: Dermatomyositis (DM) is an autoimmune disease that primarily affects the skin and muscles. It can lead to increased mortality, particularly when patients develop associated malignancies or experience fatal complications such as pulmonary fibrosis. Identifying reliable biomarkers is essential for the early diagnosis and treatment of DM. This study aims to identify and validate pivotal diagnostic biomarker for DM through integrated bioinformatics analysis and clinical sample validation.\nMethods: Gene expression datasets GSE46239 and GSE142807 from the Gene Expression Omnibus (GEO) database were merged for analysis. Differentially expressed genes (DEGs) were identified and subjected to enrichment analysis. Advanced machine learning methods were utilized to further pinpoint hub genes. Weighted gene co-expression network analysis (WGCNA) was also conducted to discover key gene modules. Subsequently, we derived intersection gene from these methods. The diagnostic performance of the candidate biomarker was evaluated using analysis with dataset GSE128314 and confirmed by immunohistochemistry (IHC) in skin lesion biopsy specimens. The CIBERSORT algorithm was used to analyze immune cell infiltration patterns in DM, then the association between the hub gene and immune cells was investigated. Gene set enrichment analysis (GSEA) was performed to understand the biomarker's biological functions. Finally, the drug-gene interactions were predicted using the DrugRep server.\nResults: Interferon-stimulated gene 15 (ISG15) was identified by intersecting DEGs, advanced machine learning-selected genes and key module genes from WGCNA. ROC analysis showed ISG15 had a high Area under the curve (AUC) of 0.950. IHC findings confirmed uniformly positive expression of ISG15, particularly in perivascular regions and lymphocytes, contrasting with universally negative expression in controls. Further analysis revealed that ISG15 is involved in abnormalities in various immune cells and inflammation-related pathways. We also predicted three drugs targeting ISG15, supported by molecular docking studies.\nConclusion: Our study identifies ISG15 as a highly specific diagnostic biomarker for DM, ISG15 may be closely related to the pathogenesis of DM, demonstrating promising potential for clinical application.", "claims": [{"id": "claim-method", "statement": "The selection of DEGs was performed using the “limma” package in R, adhering to the criteria of an |LogFC| > 1 and adj.p < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39559355", "locator": "sections[4] \"Differential expression analysis and functional correlation analysis\" paragraph 2", "quote": "The selection of DEGs was performed using the “limma” package in R, adhering to the criteria of an |LogFC| > 1 and adj.p < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39559355", "locator": "sections[28] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ISG15 was identified as a highly specific diagnostic biomarker for dermatomyositis, with an ROC-analysis AUC of 0.950.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39559355", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "ROC analysis showed ISG15 had a high Area under the curve (AUC) of 0.950."}, {"asset": "source:pmid:39559355", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our study identifies ISG15 as a highly specific diagnostic biomarker for DM, ISG15 may be closely related to the pathogenesis of DM, demonstrating promising potential for clinical application."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ISG15 was identified as a highly specific diagnostic biomarker for dermatomyositis, with an ROC-analysis AUC of 0.950.", "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:39559355"], "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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