5-Hydroxymethylcytosine signatures as diagnostic biomarkers for septic cardiomyopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40615404", "kind": "science-record", "revision": 3, "content_hash": "sha256:f6750c95f93c333373349bb58568c07e10b581175dc901e5df435113a51393ca", "created_at": "2026-11-01T20:30:42Z", "updated_at": "2026-11-01T22:14:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "5-Hydroxymethylcytosine signatures as diagnostic biomarkers for septic cardiomyopathy.", "doi": "10.1038/s41598-025-02489-8", "pmid": "40615404", "authors": ["Baixin Zhen", "Zhiling Zhao", "Hangyu Chen", "Wen Li", "Lei Zhang", "Xi Zhu", "Qinggang Ge", "Jian Lin"], "journal": "Scientific reports", "year": 2025, "abstract": "At present, there are currently no molecular biomarkers for the early diagnosis of sepsis cardiomyopathy (SCM) in clinical practice. This study focuses on an in-depth examination of the DNA hydroxymethylation profiles within plasma extracellular vesicles and explores potential molecular biomarkers during the process of SCM. The 5hmC-Seal sequencing technology was utilized to examine the hydroxymethylation modifications of extracellular vesicles DNAs in 13 patients with septic cardiomyopathy, 18 patients with sepsis without cardiomyopathy, and 8 patients without sepsis. Additionally, a diagnostic model was constructed using machine learning methods based on the differential hydroxymethylation modifications to screen for candidate biomarkers. The accuracy of the diagnostic model was 0.962, with a sensitivity and specificity of 92.3% and 88.89%, respectively. Furthermore, the diagnostic accuracy was validated using the GEO dataset, with an accuracy rate reaching 1 (GSE79962 and GSE66890), and the differential diagnostic accuracy rates also reached 0.959 and 0.944 (GSE79962). Together, the results suggest that extracellular vesicles DNAs hydroxymethylation markers can be used for diagnosis of septic cardiomyopathy.", "claims": [{"id": "claim-method", "statement": "We constructed a classification model based on the 5hmC markers from cluster 4, cluster 5, and cluster 8 obtained through temporal clustering analysis, using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40615404", "locator": "sections[24] \"Diagnostic model based on 5hmC markers can effectively diagnose SCM\" paragraph 2", "quote": "We constructed a classification model based on the 5hmC markers from cluster 4, cluster 5, and cluster 8 obtained through temporal clustering analysis, using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusions of this article are included within the article and its Supplementary files. The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive of the BIG Data Center at the Beijing Institute of Genomics, Chinese Academy of Science, under accession number HRA008552 (accessible at https://ngdc.cncb.ac.cn/gsa-human). Code is available from the corresponding author on reason able request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40615404", "locator": "sections[33] \"notes\" paragraph 1", "quote": "The datasets supporting the conclusions of this article are included within the article and its Supplementary files. The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive of the BIG Data Center at the Beijing Institute of Genomics, Chinese Academy of Science, under accession number HRA008552 (accessible at https://ngdc.cncb.ac.cn/gsa-human). Code is available from the corresponding author on reason able request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The 5hmC-marker diagnostic model achieved an accuracy of 0.962, with 92.3% sensitivity and 88.89% specificity, and extracellular vesicle DNA hydroxymethylation markers could be used to diagnose septic cardiomyopathy.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40615404", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The accuracy of the diagnostic model was 0.962, with a sensitivity and specificity of 92.3% and 88.89%, respectively."}, {"asset": "source:pmid:40615404", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Together, the results suggest that extracellular vesicles DNAs hydroxymethylation markers can be used for diagnosis of septic cardiomyopathy."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The 5hmC-marker diagnostic model achieved an accuracy of 0.962, with 92.3% sensitivity and 88.89% specificity, and extracellular vesicle DNA hydroxymethylation markers could be used to diagnose septic cardiomyopathy.", "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:40615404"], "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:GSE66890"], "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:GSE66890"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40615404", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-025-02489-8", "sha256": "sha256:a2f06fbdc404dc69030b28628bdb12db5cec514c9092aefb9714e0d3b3badcee", "bytes": 44553, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-025-02489-8", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12227685", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE66890", "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=GSE66890", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE66890", "version": null, "note": "The datasets supporting the conclusions of this article are included within the article and its Supplementary files. The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive of the BIG Data Center at the Beijing Institute of Genomics, Chinese Academy of Science, under accession number HRA008552 (accessible at https://ngdc.cncb.ac.cn/gsa-human). Code is available from the corresponding author on reason able request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets supporting the conclusions of this article are included within the article and its Supplementary files. The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive of the BIG Data Center at the Beijing Institute of Genomics, Chinese Academy of Science, under accession number HRA008552 (accessible at https://ngdc.cncb.ac.cn/gsa-human). Code is available from the corresponding author on reason able request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1633778", "GSM1633779", "GSM1633780", "GSM1633781", "GSM1633782", "GSM1633783", "GSM1633784", "GSM1633785", "GSM1633786", "GSM1633787", "GSM1633788", "GSM1633789", "GSM1633790", "GSM1633791", "GSM1633792", "GSM1633793", "GSM1633794", "GSM1633795", "GSM1633796", "GSM1633797", "GSM1633798", "GSM1633799", "GSM1633800", "GSM1633801", "GSM1633802", "GSM1633803", "GSM1633804", "GSM1633805", "GSM1633806", "GSM1633807", "GSM1633808", "GSM1633809", "GSM1633810", "GSM1633811", "GSM1633812", "GSM1633813", "GSM1633814", "GSM1633815", "GSM1633816", "GSM1633817", "GSM1633818", "GSM1633819", "GSM1633820", "GSM1633821", "GSM1633822", "GSM1633823", "GSM1633824", "GSM1633825", "GSM1633826", "GSM1633827", "GSM1633828", "GSM1633829", "GSM1633830", "GSM1633831", "GSM1633832", "GSM1633833", "GSM1633834", "GSM1633835", "GSM1633836", "GSM1633837", "GSM1633838", "GSM1633839"], "sample_count": 62, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Expression of Neutrophil-related genes in patients with early sepsis-induced ARDS", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE79962", "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=GSE79962", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE79962", "version": null, "note": "The datasets supporting the conclusions of this article are included within the article and its Supplementary files. The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive of the BIG Data Center at the Beijing Institute of Genomics, Chinese Academy of Science, under accession number HRA008552 (accessible at https://ngdc.cncb.ac.cn/gsa-human). Code is available from the corresponding author on reason able request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets supporting the conclusions of this article are included within the article and its Supplementary files. The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive of the BIG Data Center at the Beijing Institute of Genomics, Chinese Academy of Science, under accession number HRA008552 (accessible at https://ngdc.cncb.ac.cn/gsa-human). Code is available from the corresponding author on reason able request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2109130", "GSM2109131", "GSM2109132", "GSM2109133", "GSM2109134", "GSM2109135", "GSM2109136", "GSM2109137", "GSM2109138", "GSM2109139", "GSM2109140", "GSM2109141", "GSM2109142", "GSM2109143", "GSM2109144", "GSM2109145", "GSM2109146", "GSM2109147", "GSM2109148", "GSM2109149", "GSM2109150", "GSM2109151", "GSM2109152", "GSM2109153", "GSM2109154", "GSM2109155", "GSM2109156", "GSM2109157", "GSM2109158", "GSM2109159", "GSM2109160", "GSM2109161", "GSM2109162", "GSM2109163", "GSM2109164", "GSM2109165", "GSM2109166", "GSM2109167", "GSM2109168", "GSM2109169", "GSM2109170", "GSM2109171", "GSM2109172", "GSM2109173", "GSM2109174", "GSM2109175", "GSM2109176", "GSM2109177", "GSM2109178", "GSM2109179", "GSM2109180"], "sample_count": 51, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Widespread downregulation of cardiac mitochondrial and sarcomeric genes in patients with sepsis", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE66890 not downloaded", "asset:data:geo:GSE66890 licence not read", "asset:data:geo:GSE79962 not downloaded", "asset:data:geo:GSE79962 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-2", "family": "differential_expression", "specific": "deseq2", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "DESeq2"}}, {"id": "method-3", "family": null, "specific": null, "label": "Least Absolute Shrinkage and Selection Operator (LASSO)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We constructed a classification model based on the 5hmC markers from cluster 4, cluster 5, and cluster 8 obtained through temporal clustering analysis, using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE66890", "GSE79962"], "resolved_accessions": ["GSE66890", "GSE79962"], "statements": ["The datasets supporting the conclusions of this article are included within the article and its Supplementary files. The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive of the BIG Data Center at the Beijing Institute of Genomics, Chinese Academy of Science, under accession number HRA008552 (accessible at https://ngdc.cncb.ac.cn/gsa-human). Code is available from the corresponding author on reason able request."], "basis": "The paper names GSE66890, GSE79962 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:40615404", "data:geo:GSE66890"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE66890"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:56:06Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12502, "completion_tokens": 1625, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:40615404", "type": "paper", "label": "pmid:40615404"}, {"id": "source:pmid:40615404", "type": "manuscript", "label": "PMID 40615404 full text"}, {"id": "data:geo:GSE66890", "type": "dataset", "label": "GEO GSE66890"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40615404", "type": "paper", "label": "pmid:40615404"}, {"id": "source:pmid:40615404", "type": "manuscript", "label": "PMID 40615404 full text"}, {"id": "data:geo:GSE66890", "type": "dataset", "label": "GEO GSE66890"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40615404", "type": "extraction", "used": ["source:pmid:40615404"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE66890", "type": "accession_resolution", "used": ["data:geo:GSE66890"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:40615404", "parent_hash": "sha256:82c7b766b4d5e6c1d6bc812503a12fc9d574b6f6ef792d28e6a39717b3e8efab", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE66890 licence not read", "asset:data:geo:GSE66890 not downloaded", "asset:data:geo:GSE79962 licence not read", "asset:data:geo:GSE79962 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["ANOVA"], "order_basis": "analysis_only", "id": "assay:1"}]}