{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40909264", "kind": "science-record", "revision": 3, "content_hash": "sha256:a59d879154ec8f1b5e9002b27f8f996135ccd95647940c52cbee75df4c8677ab", "created_at": "2026-11-01T20:31:01Z", "updated_at": "2026-11-01T22:14:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of cuproptosis-related genes in chronic apical periodontitis based on bulk and single-cell RNA sequencing analyses and experimental validation.", "doi": "10.3389/fimmu.2025.1559220", "pmid": "40909264", "authors": ["Caiyi Zhang", "Jie Zhao", "Keqing Pan", "Lingshuang Liu", "Mengyu Jiao", "Changqing Yuan", "Chunyan Wan"], "journal": "Frontiers in immunology", "year": 2025, "abstract": "Background: Chronic apical periodontitis (CAP) is a prevalent oral inflammatory disease, yet the complex mechanisms underlying its etiology remain unclear. A recently identified cell death pathway known as cuproptosis may be linked to this condition.\nMethods: Differentially expressed cuproptosis-related genes (DE-CRGs) were identified by integrating human CAP dataset (GSE237398) with health control (HC) dataset (GSE223924) from the Gene Expression Omnibus (GEO) database. Subsequently, single-cell RNA sequencing (scRNA-seq) data from clinical samples with CAP (n=3) and HC (n=3) from the GSE171213 dataset were analyzed to assess variations across different cell clusters. The association of CRGs with macrophages and fibroblasts in periodontitis was then explored. Fibroblasts and macrophages were selected for further analysis, which included subset classification, cell-chat analysis, and functional enrichment analysis. Additionally, Receiver Operating Characteristic (ROC) curves were employed to evaluate the discriminatory ability of gene features. Changes in DE-CRGs within the whole periodontitis tissue were confirmed through quantitative real-time PCR (qRT-PCR) and immumohistochemical staining (IHC).\nResults: Eight CAP-related DE-CRGs were identified through bulk mRNA sequencing. Numerous interactions among these CRGs were observed, highlighting the complexity of protein-protein interactions. ROC curve analysis demonstrated strong diagnostic potential for these genes. ScRNA-seq sequencing revealed significant alterations in CRGs within fibroblasts and macrophages, along with close intercellular communication between these cell clusters. qRT-PCR and IHC analysis of clinical samples further confirmed DE-CRGs expression in CAP.\nConclusion: These findings suggest that CRGs are closely associated with the COL4A1-Fibro and APOE-Macro intercellular interactions, which may facilitate the occurrence and progression of cuproptosis in chronic apical periodontitis.", "claims": [{"id": "claim-method", "statement": "To evaluate the diagnostic performance of the predictive model, a Receiver Operating Characteristic (ROC) curve was generated.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40909264", "locator": "sections[7] \"Construction of the prognostic model\" paragraph 2", "quote": "To evaluate the diagnostic performance of the predictive model, a Receiver Operating Characteristic (ROC) curve was generated."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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The names of the repository/repositories and accession number(s) can be found below: PRJNA1213680 (SRA)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The results indicated that CRGs demonstrated strong diagnostic performance in the training set except DLST, GCSH or LIAS (AUC > 0.8, Figure 7K ).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40909264", "locator": "sections[25] \"Construction of the prognostic model with CRGs\" paragraph 2", "quote": "The results indicated that CRGs demonstrated strong diagnostic performance in the training set except DLST, GCSH or LIAS (AUC > 0.8, Figure 7K )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The results indicated that CRGs demonstrated strong diagnostic performance in the training set except DLST, GCSH or LIAS (AUC > 0.8, Figure 7K ).", "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:40909264"], "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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Subsequently, single-cell RNA sequencing (scRNA-seq) data from clinical samples with", "e. Subsequently, single-cell RNA sequencing (scRNA-seq) data from clinical samples with CAP (n=3) a", "strong diagnostic potential for these genes. ScRNA-seq sequencing revealed significant alterations"], "order_basis": "paper_text_order:49", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["periodontitis based on bulk and single-cell RNA sequencing analyses and experimental validation.", "us (GEO) database. 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The positive signals were predomin"], "order_basis": "paper_text_order:1268", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["(qRT-PCR) and immumohistochemical staining (IHC). Results: Eight CAP-related DE-CRGs were id", "ion between these cell clusters. qRT-PCR and IHC analysis of clinical samples further confirm", "dicted downregulation of NFE2L2 and SLC25A3, immunohistochemical results demonstrated significantly increased", "(n = 5) and CAP tissue (n = 5) evaluated by IHC. 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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}}}