Identification and validation of key biomarkers based on RNA methylation genes in sepsis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37701433", "kind": "science-record", "revision": 3, "content_hash": "sha256:7fec15c795d4416b997eba592a1af6e66b734ec68d7ee968e662eb42eb972768", "created_at": "2026-11-01T19:02:31Z", "updated_at": "2026-11-01T22:10:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of key biomarkers based on RNA methylation genes in sepsis.", "doi": "10.3389/fimmu.2023.1231898", "pmid": "37701433", "authors": ["Qianqian Zhang", "Xiaowei Bao", "Mintian Cui", "Chunxue Wang", "Jinlu Ji", "Jiongjie Jing", "Xiaohui Zhou", "Kun Chen", "Lunxian Tang"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: RNA methylation is closely involved in immune regulation, but its role in sepsis remains unknown. Here, we aim to investigate the role of RNA methylation-associated genes (RMGs) in classifying and diagnosing of sepsis.\nMethods: Five types of RMGs (m1A, m5C, m6Am, m7G and Ψ) were used to identify sepsis subgroups based on gene expression profile data obtained from the GEO database (GSE57065, GSE65682, and GSE95233). Unsupervised clustering analysis was used to identify distinct RNA modification subtypes. The CIBERSORT, WGCNA, GO and KEGG analysis were performed to explore immune infiltration pattern and biological function of each cluster. RF, SVM, XGB, and GLM algorithm were applied to identify the diagnostic RMGs in sepsis. Finally, the expression levels of the five key RMGs were verified by collecting PBMCs from septic patients using qRT-PCR, and their diagnostic efficacy for sepsis was verified in combination with clinical data using ROC analysis.\nResults: Sepsis was divided into three subtypes (cluster 1 to 3). Cluster 1 highly expressed NSUN7 and TRMT6, with the characteristic of neutrophil activation and upregulation of MAPK signaling pathways. Cluster 2 highly expressed NSUN3, and was featured by the regulation of mRNA stability and amino acid metabolism. NSUN5 and NSUN6 were upregulated in cluster 3 which was involved in ribonucleoprotein complex biogenesis and carbohydrate metabolism pathways. In addition, we identified that five RMGs (NSUN7, NOP2, PUS1, PUS3 and FTO) could function as biomarkers for clinic diagnose of sepsis. For validation, we determined that the relative expressions of NSUN7, NOP2, PUS1 and PUS3 were upregulated, while FTO was downregulated in septic patients. The area under the ROC curve (AUC) of NSUN7, NOP2, PUS1, PUS3 and FTO was 0.828, 0.707, 0.846, 0.834 and 0.976, respectively.\nConclusions: Our study uncovered that dysregulation of RNA methylation genes (m1A, m5C, m6Am, m7G and Ψ) was closely involved in the pathogenesis of sepsis, providing new insights into the classification of sepsis endotypes. We also revealed that five hub RMGs could function as novel diagnostic biomarkers and potential targets for treatment.", "claims": [{"id": "claim-method", "statement": "The AUC of NSUN7, NOP2, PUS1, PUS3 and FTO at day 1 was 0.828, 0.707, 0.846, 0.834 and 0.976 respectively ( Figure 10B ).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37701433", "locator": "sections[23] \"The validation of diagnostic value of the five hub RMGs in clinical settings\" paragraph 5", "quote": "The AUC of NSUN7, NOP2, PUS1, PUS3 and FTO at day 1 was 0.828, 0.707, 0.846, 0.834 and 0.976 respectively ( Figure 10B )."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available databases were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/, GSE57065, GSE65682, and GSE95233.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37701433", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "Publicly available databases were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/, GSE57065, GSE65682, and GSE95233."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In addition, we identified that five RMGs (NSUN7, NOP2, PUS1, PUS3 and FTO) could function as biomarkers for clinic diagnose of sepsis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37701433", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In addition, we identified that five RMGs (NSUN7, NOP2, PUS1, PUS3 and FTO) could function as biomarkers for clinic diagnose of sepsis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "In addition, we identified that five RMGs (NSUN7, NOP2, PUS1, PUS3 and FTO) could function as biomarkers for clinic diagnose of sepsis.", "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:37701433"], "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:GSE57065"], "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_mann_whitney", "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:GSE57065"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37701433", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1231898", "sha256": "sha256:81f019c92114484681847b5650d0953ee962a5290a247594f8fbf7fbba23a7a9", "bytes": 64402, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1231898", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10493392", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE57065", "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=GSE57065", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE57065", "version": null, "note": "Publicly available databases were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/, GSE57065, GSE65682, and GSE95233.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available databases were analyzed in this study. 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