{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41144543", "kind": "science-record", "revision": 3, "content_hash": "sha256:f6615e23d2c903862338a35511bb3f6d7696bc49194748021deb44db70eb9d5e", "created_at": "2026-11-01T20:31:11Z", "updated_at": "2026-11-01T22:14:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of cuproptosis-related genes in diabetic cardiomyopathy.", "doi": "10.1371/journal.pone.0328512", "pmid": "41144543", "authors": ["Jun Li", "Hua Zhang", "Xinyue Duan", "Meina Zhang", "Xin Li", "Chunyan Hao"], "journal": "PloS one", "year": 2025, "abstract": "BACKGROUND: Diabetic cardiomyopathy (DCM) represents a distinct myocardial pathology arising from chronic diabetic metabolic disturbances, characterized by progressive structural and functional abnormalities that frequently culminate in heart failure. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, studies are limited on the clinical significance of cuproptosis-related genes (CRGs) in DCM. Therefore, it is helpful to identify CRGs involved in DCM and explore their expression and molecular mechanisms.\nMETHODS: We downloaded three datasets of DCM from the GEO database and a set of cuproptosis-related genes with 176 genes. Following the identification of the differentially expressed cuproptosis-related genes(DECRGs) and hub genes, we performed the functional annotation, protein-protein interaction network, co-expression network analysis, mRNA-miRNA regulatory network.The GSE5606 dataset was then used to verify hub genes. Finally, we validated the expression of hub genes in a high glucose-induced H9C2 cell injury model via RT-qPCR.\nRESULTS: We identified 14 DEFRGs and 7 key genes in the DCM samples compared to the control. Functional enrichment analysis revealed that DECRGs are associated with several pathways, including TCA cycle, respiratory electron transport, oxidative stress, and metabolism pathway. Moreover, Isocitrate dehydrogenase 1(Idh1), Cytochrome P450 Family 1 Subfamily A Member 1(Cyp1a1), 3-Hydroxy-3-Methylglutaryl-CoA Synthase (Hmgcs2) and Hexokinase 2(Hk2) were identified as the hub genes and validated in the GSE5606 datasets with area under the curve(AUC)>0.7. The qRT-PCR results showed that the expression levels of Cyp1a1, Hmgcs2, HK2, and Idh1 in vitro model of DCM and controls were consistent with the bioinformatics analysis results from the mRNA microarray.\nCONCLUSIONS: Overall,we identified hub genes and pathways involved in DCM via bioinformatics analysis and revealed the potential role of cuproptosis, providing useful and novel information to explore the potential candidate genes for DCM diagnostic and therapeutic options.", "claims": [{"id": "claim-method", "statement": "The expression data of 7 hub genes were extracted, and groups were compared using the Student’s t-test. To evaluate the diagnostic performance of 7 hub genes, the ROC was plotted using the“pROC”R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41144543", "locator": "sections[10] \"Validation of hub genes in GSE5606\" paragraph 2", "quote": "The expression data of 7 hub genes were extracted, and groups were compared using the Student’s t-test. To evaluate the diagnostic performance of 7 hub genes, the ROC was plotted using the“pROC”R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the manuscript and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41144543", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the manuscript and its Supporting Information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 14 differentially expressed cuproptosis-related genes and 7 hub genes, with Idh1, Cyp1a1, Hmgcs2, and Hk2 showing AUC values greater than 0.7 in the GSE5606 validation dataset.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41144543", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 14 DEFRGs and 7 key genes in the DCM samples compared to the control."}, {"asset": "source:pmid:41144543", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Moreover, Isocitrate dehydrogenase 1(Idh1), Cytochrome P450 Family 1 Subfamily A Member 1(Cyp1a1), 3-Hydroxy-3-Methylglutaryl-CoA Synthase (Hmgcs2) and Hexokinase 2(Hk2) were identified as the hub genes and validated in the GSE5606 datasets with area under the curve(AUC)>0.7."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 14 differentially expressed cuproptosis-related genes and 7 hub genes, with Idh1, Cyp1a1, Hmgcs2, and Hk2 showing AUC values greater than 0.7 in the GSE5606 validation dataset.", "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:41144543"], "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:GSE267352"], "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:GSE267352"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41144543", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0328512", "sha256": 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"verbatim", "quote": "The expression data of 7 hub genes were extracted, and groups were compared using the Student’s t-test. To evaluate the diagnostic performance of 7 hub genes, the ROC was plotted using the“pROC”R package."}}], "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE4745", "GSE6880", "GSE5606", "GSE267352"], "resolved_accessions": ["GSE4745", "GSE6880", "GSE5606", "GSE267352"], "statements": ["All relevant data are within the manuscript and its Supporting Information files."], "basis": "The paper names GSE4745, GSE6880, GSE5606, GSE267352 in Gene Expression Omnibus (GEO), NCBI and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:41144543", "data:geo:GSE267352"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE267352"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:04:03Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14131, "completion_tokens": 1702, "cached_tokens": 128}}, "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:41144543", "type": "paper", "label": "pmid:41144543"}, {"id": "source:pmid:41144543", "type": "manuscript", "label": "PMID 41144543 full text"}, {"id": "data:geo:GSE267352", "type": "dataset", "label": "GEO GSE267352"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41144543", "type": "paper", "label": "pmid:41144543"}, {"id": "source:pmid:41144543", "type": "manuscript", "label": "PMID 41144543 full text"}, {"id": "data:geo:GSE267352", "type": "dataset", "label": "GEO GSE267352"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41144543", "type": "extraction", "used": ["source:pmid:41144543"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE267352", "type": "accession_resolution", "used": ["data:geo:GSE267352"], "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:41144543", "parent_hash": "sha256:eb11fbabd53b7e253284f6a37b9300db77144ca9c8b41f32b2ae3f2559bc0946", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE267352 licence not read", "asset:data:geo:GSE267352 not downloaded", "asset:data:geo:GSE4745 licence not read", "asset:data:geo:GSE4745 not downloaded", "asset:data:geo:GSE5606 licence not read", "asset:data:geo:GSE5606 not downloaded", "asset:data:geo:GSE6880 licence not read", "asset:data:geo:GSE6880 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["h glucose-induced H9C2 cell injury model via RT-qPCR. RESULTS: We identified 14 DEFRGs and 7 key", "lucose-induced H9C2 cell injury model via RT-qPCR. RESULTS: We identified 14 DEFRGs and 7 key"], "order_basis": "paper_text_order:1154", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ioinformatics analysis results from the mRNA microarray. CONCLUSIONS: Overall,we identified hub gene"], "order_basis": "paper_text_order:1911", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.642, "evidence": ["and establishment of vitro model of DCM H9C2 rat cardiomyocytes were purchased from Wuhan Pri"], "order_basis": "paper_text_order:2282", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ella Biotechnology Co., Ltd. H9c2 cells were cultured in DMEM medium containing 10% FBS, 100 U/ml pen", "nd 100 μg/ml streptomycin in 5%CO2,37°C, and passaged or punched when cells grew to about 80% to 9"], "order_basis": "paper_text_order:2376", "id": "assay:4"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:5"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. 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At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}