{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39779817", "kind": "science-record", "revision": 4, "content_hash": "sha256:b525b22666513f439e88a3e5903935db9c91a099690abba7bddd5c8f570e95ef", "created_at": "2026-11-01T20:30:06Z", "updated_at": "2026-11-01T22:55:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a novel disulfidptosis-related gene signature in osteoarthritis using bioinformatics analysis and experimental validation.", "doi": "10.1038/s41598-025-85569-z", "pmid": "39779817", "authors": ["Mingjie Wei", "Xiangwen Shi", "Wenbao Tang", "Qian Lv", "Yipeng Wu", "Yongqing Xu"], "journal": "Scientific reports", "year": 2025, "abstract": "Osteoarthritis (OA) is a degenerative bone disease characterized by the destruction of joint cartilage and synovial inflammation, involving intricate immune regulation processes. Disulfidptosis, a novel form of programmed cell death, has recently been identified; however, the effects and roles of disulfidptosis-related genes (DR-DEGs) in OA remain unclear. We obtained six OA datasets from the GEO database, using four as training sets and two as validation sets. Differential expression analysis was employed to identify DR-DEGs, and unique molecular subtypes of OA were constructed based on these DR-DEGs. Subsequently, the immune microenvironment of OA patients was comprehensively analyzed using the \"CIBERSORT\" algorithm for immune infiltration. Various machine learning algorithms were utilized to screen characteristic DR-DEGs, and nomogram models and ROC curves were built based on these genes. The scRNA dataset (GSE169454) was used to classify chondrocytes in OA samples into distinct cell types, further exploring the gene distribution and correlation of characteristic DR-DEGs with specific cell subpopulations. Moreover, the expression levels of four characteristic DR-DEGs were validated through OA cell models and rat models. In our study, we identified 10 DR-DEGs with significant differences in expression within OA samples. Based on these DR-DEGs, two distinct molecular subtypes were recognized (cluster 1 and 2). ZNF484 and NDUFS1 were found to be significantly overexpressed in subtype 1, while the infiltration abundance of activated mast cells was markedly elevated in subtype 2. Moreover, significant differences were observed in the infiltration proportions of 11 immune cell types between OA and control samples, with 9 DR-DEGs demonstrating substantial correlations with immune cell infiltration levels. Further analysis of the scRNA dataset revealed that SLC3A2 and NDUFC1 were predominantly expressed in the preHTC subpopulation. All 10 DR-DEGs exhibited notably higher expression in the EC subpopulation across various cell types. The proportion of EC subgroups with high SLC3A2 expression increased, mainly enriching pathways related to inflammation, such as the IL-17 signaling pathway and TGF-beta signaling pathway. Using machine learning, we identified four characteristic DR-DEGs, which, in combination with the nomogram and ROC models, demonstrated promising performance in the diagnosis of OA. Additionally, in vivo validation confirmed a significant elevation of PPM1F expression in OA models. This study identified DR-DEGs as potential biomarkers for the diagnosis and classification of OA and provided a preliminary understanding of their role in the immune microenvironment. However, further experimental and clinical studies are required to validate their diagnostic value and therapeutic potential.", "claims": [{"id": "claim-method", "statement": "To extract DR-DEGs in OA patients, we utilized the “limma” package17 to perform differential expression analysis of genes between the OA and control groups, which included upregulated and downregulated genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39779817", "locator": "sections[4] \"Identification of disulfidptosis-related differentially expressed genes (DR-DEGs)\" paragraph 2", "quote": "To extract DR-DEGs in OA patients, we utilized the “limma” package17 to perform differential expression analysis of genes between the OA and control groups, which included upregulated and downregulated genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data used to support the findings of this study can be downloaded from the GSE51588, GSE55235, GSE55457, GSE117999, GSE167077 and GSE169454 datasets (https://www.ncbi.nlm.nih.gov/geo). The processed data are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39779817", "locator": "sections[36] \"Data availability\" paragraph 2", "quote": "The microarray data used to support the findings of this study can be downloaded from the GSE51588, GSE55235, GSE55457, GSE117999, GSE167077 and GSE169454 datasets (https://www.ncbi.nlm.nih.gov/geo). The processed data are available from the corresponding author upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Four characteristic DR-DEGs were identified by integrating multiple machine-learning algorithms, and the resulting logistic-regression model achieved an AUC of 0.873 in the validation set.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39779817", "locator": "sections[28] \"Diagnostic value of characteristic DR-DEGs in OA\" paragraph 2", "quote": "In the validation set ROC curves, the AUC values for SLC3A2 and LRPPRC were both greater than 0.700, and the AUC value for the logistics regression model was 0.873 (Fig. 10F and G)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Four characteristic DR-DEGs were identified by integrating multiple machine-learning algorithms, and the resulting logistic-regression model achieved an AUC of 0.873 in the validation set.", "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:39779817"], "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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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE51588", "GSE55235", "GSE55457", "GSE77298", "GSE117999", "GSE169077", "GSE169454", "GSE167077"], "resolved_accessions": ["GSE51588", "GSE55235", "GSE55457", "GSE77298", "GSE117999", "GSE169077", "GSE169454", "GSE167077"], "statements": ["The microarray data used to support the findings of this study can be downloaded from the GSE51588, GSE55235, GSE55457, GSE117999, GSE167077 and GSE169454 datasets (https://www.ncbi.nlm.nih.gov/geo). The processed data are available from the corresponding author upon request."], "basis": "The paper names GSE51588, GSE55235, GSE55457, GSE77298, GSE117999, GSE169077, GSE169454, GSE167077 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:39779817", "data:geo:GSE117999"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE117999"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:44:29Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15898, "completion_tokens": 2343, "cached_tokens": 0}}, "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:39779817", "type": "paper", "label": "pmid:39779817"}, {"id": "source:pmid:39779817", "type": "manuscript", "label": "PMID 39779817 full text"}, {"id": "data:geo:GSE117999", "type": "dataset", "label": "GEO GSE117999"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39779817", "type": "paper", "label": "pmid:39779817"}, {"id": "source:pmid:39779817", "type": "manuscript", "label": "PMID 39779817 full text"}, {"id": "data:geo:GSE117999", "type": "dataset", "label": "GEO GSE117999"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39779817", "type": "extraction", "used": ["source:pmid:39779817"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE117999", "type": "accession_resolution", "used": ["data:geo:GSE117999"], "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:39779817", "parent_hash": "sha256:04a2947e08242327cf05a59ee64018bc11d8d34a8d754a4ab72f243c1e83e06e", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE117999 licence not read", "asset:data:geo:GSE117999 not downloaded", "asset:data:geo:GSE167077 licence not read", "asset:data:geo:GSE167077 not downloaded", "asset:data:geo:GSE169077 licence not read", "asset:data:geo:GSE169077 not downloaded", "asset:data:geo:GSE169454 licence not read", "asset:data:geo:GSE169454 not downloaded", "asset:data:geo:GSE51588 licence not read", "asset:data:geo:GSE51588 not downloaded", "asset:data:geo:GSE55235 licence not read", "asset:data:geo:GSE55235 not downloaded", "asset:data:geo:GSE55457 licence not read", "asset:data:geo:GSE55457 not downloaded", "asset:data:geo:GSE77298 licence not read", "asset:data:geo:GSE77298 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rmance in the diagnosis of OA. Additionally, in vivo validation confirmed a significant elevation", "Gs were validated through OA cell models and rat models. In our study, we identified 10 DR-DE", "ate the expression of characteristic DR-DEGs in vivo, we established an OA rat model. A total of", "utured layer by layer. Four weeks later, the rats were euthanized using cervical dislocation, and t"], "order_basis": "paper_text_order:1327", "id": "assay:1"}, {"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": ["characteristic DR-DEGs in OA tissues through RT-qPCR revealed that except for GYS1, whose mRNA le", "firming the bioinformatics analysis results. RT-qPCR validation of key DR-DEGs. (A) The expressio", "n the two groups, it was consistent with the RT-qPCR results. These results suggest that the tren", "racteristic DR-DEGs in OA tissues through RT-qPCR revealed that except for GYS1, whose mRNA le"], "order_basis": "paper_text_order:5974", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["oup were compared (Fig. 11B). The results of Western Blot analysis indicated that the protein level of"], "order_basis": "paper_text_order:6723", "id": "assay:3"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["To extract DR-DEGs in OA patients, we utilized the “limma” package17 to perform differential expression analysis of genes between the OA and control groups, which included upregulated and downregulated genes."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]},"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. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T01:45:47+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. 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}}}