5mC modification patterns provide novel direction for early acute myocardial infarction detection and personalized therapy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36620624", "kind": "science-record", "revision": 3, "content_hash": "sha256:2f0bf56df508bf0e61a8402a99941e3ba5bf19768b38023c5d1216b219914e6c", "created_at": "2026-11-01T19:01:10Z", "updated_at": "2026-11-01T22:08:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "5mC modification patterns provide novel direction for early acute myocardial infarction detection and personalized therapy.", "doi": "10.3389/fcvm.2022.1053697", "pmid": "36620624", "authors": ["Yiqun Guo", "Hua Jiang", "Jinlong Wang", "Ping Li", "Xiaoquan Zeng", "Tao Zhang", "Jianyi Feng", "Ruqiong Nie", "Yulong Liu", "Xiaobian Dong", "Qingsong Hu"], "journal": "Frontiers in cardiovascular medicine", "year": 2022, "abstract": "Background: Most deaths from coronary artery disease (CAD) are due to acute myocardial infarction (AMI). There is an urgent need for early AMI detection, particularly in patients with stable CAD. 5-methylcytosine (5mC) regulatory genes have been demonstrated to involve in the progression and prognosis of cardiovascular diseases, while little research examined 5mC regulators in CAD to AMI progression.\nMethod: Two datasets (GSE59867 and GSE62646) were downloaded from Gene Expression Omnibus (GEO) database, and 21 m5C regulators were extracted from previous literature. Dysregulated 5mC regulators were screened out by \"limma.\" The least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithm were employed to identify hub 5mC regulators in CAD to AMI progression, and 43 clinical samples (Quantitative real-time PCR) were performed for expression validation. Then a logistic model was built to construct 5mC regulator signatures, and a series of bioinformatics algorithms were performed for model validation. Besides, 5mC-associated molecular clusters were studied via unsupervised clustering analysis, and correlation analysis between immunocyte and 5mC regulators in each cluster was conducted.\nResults: Nine hub 5mC regulators were identified. A robust model was constructed, and its prominent classification accuracy was verified via ROC curve analysis (area under the curve [AUC] = 0.936 in the training cohort and AUC = 0.888 in the external validation cohort). Besides, the clinical effect of the model was validated by decision curve analysis. Then, 5mC modification clusters in AMI patients were identified, along with the immunocyte infiltration levels of each cluster. The correlation analysis found the strongest correlations were TET3-Mast cell in cluster-1 and TET3-MDSC in cluster-2.\nConclusion: Nine hub 5mC regulators (DNMT3B, MBD3, UHRF1, UHRF2, NTHL1, SMUG1, ZBTB33, TET1, and TET3) formed a diagnostic model, and concomitant results unraveled the critical impact of 5mC regulators, providing interesting epigenetics findings in AMI population vs. stable CAD.", "claims": [{"id": "claim-method", "statement": "The expression status of the hub 5mC regulators were compared between admission and other time points using Wilcoxon rank sum test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36620624", "locator": "sections[13] \"2.11 Association of identified 5mC regulators and AMI\" paragraph 2", "quote": "The expression status of the hub 5mC regulators were compared between admission and other time points using Wilcoxon rank sum test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36620624", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Besides, the clinical effect of the model was validated by decision curve analysis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36620624", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Nine hub 5mC regulators (DNMT3B, MBD3, UHRF1, UHRF2, NTHL1, SMUG1, ZBTB33, TET1, and TET3) formed a diagnostic model, and concomitant results unraveled the critical impact of 5mC regulators, providing interesting epigenetics findings in AMI population vs. stable CAD."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Besides, the clinical effect of the model was validated by decision curve analysis.", "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:36620624"], "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:GSE59867"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE59867"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36620624", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2022.1053697", "sha256": "sha256:16fc1c80105db43439a2d051bdfaad6d990cb126645b79d857f4d70d80e56f02", "bytes": 50803, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2022.1053697", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9816341", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE59867", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59867", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE59867", "version": null, "note": "Publicly available datasets were analyzed in this study. 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