{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40289127", "kind": "science-record", "revision": 2, "content_hash": "sha256:73df152ef8a34b988baea12d12583dedef8767873697b701ed4df11ec8af8c54", "created_at": "2026-11-01T20:30:27Z", "updated_at": "2026-11-01T21:35:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring the molecular mechanisms underlying intervertebral disc degeneration by analysing multiple datasets.", "doi": "10.1038/s41598-025-98070-4", "pmid": "40289127", "authors": ["Longquan Lin", "Da Li", "Gangfeng Cai", "Gengyang Zheng", "Dianfeng Huang", "Hua Liu", "Shunxin Lin", "Feng Zhao"], "journal": "Scientific reports", "year": 2025, "abstract": "The purpose of this study was to explore the genetic characteristics and immune cell infiltration related to intervertebral disc degeneration through multidataset analysis, predict potential therapeutic drugs, and provide a theoretical basis for clinical treatment. The gene expression profile data of the GSE70362, GSE186542, and GSE245147 datasets were downloaded from the Gene Expression Omnibus (GEO) database, and the hub genes were identified through differentially expressed gene analysis, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) functional annotation and Mendelian randomization analysis were performed. Hub genes and immune cells were identified. Infiltration status was determined through GSEA and GSVA to clarify the specific signalling pathways associated with key genes and explore the potential molecular mechanisms by which key genes affect disease progression. The key genes were reversely predicted using miRNA grid construction and transcription factor regulation, and genes related to disease regulation were obtained from the GeneCards database. Finally, the differentially expressed genes were used for drug prediction through the Connectivity Map database to identify potential drugs for the treatment of intervertebral disc degeneration. The feasibility of the predicted drugs was tested by molecular docking technology. Real-time quantitative PCR was used to confirm the expression of key genes in the tissue samples.A total of 126 differentially expressed genes were identified in the GEO database, and 4 differentially expressed hub genes (COL6A2, DCXR, GLRX, and PDGFRB) were identified through bioinformatics methods. Immune infiltration analysis revealed that NK cells, macrophages, and eosinophils were activated during IVDD, whereas mast cells and T cells were suppressed. GO and KEGG analyses revealed that key genes are involved in the development of this disease through signalling pathways such as the glycolysis pathway, the oxidative phosphorylation pathway, the cholesterol regulatory pathway, and the haem metabolism pathway. Analysis of the constructed miRNA grid revealed that key genes are jointly regulated by multiple transcription factors, among which the most important motif is cisbp_M5578. Disease regulation-related genes were obtained through the GeneCards database, analysis of the correlation with key genes was performed, and the expression levels of the two mRNA and miRNA were significantly correlated. Finally, drug prediction performed through the Connectivity Map database revealed that drugs such as Abt-751, LY-2183240, podophyllotoxin, and vindesine can alleviate or even reverse the disease state. Finally, we collected 10 IVDD and 10 healthy disc tissue samples, and the RT‒qPCR results were consistent with the bioinformatics results. We identified COL6A2, DCXR, GLRX, and PDGFRB as key genes involved in IVDD. In addition, drugs such as Abt-751 are expected to control and reverse the progression of the disease. In the future, these key genes and predicted drugs may provide new directions for further mechanistic studies as well as new therapies for IVDD patients.", "claims": [{"id": "claim-method", "statement": "We used Mendelian randomization methods to provide more reliable causal inference, thereby clarifying the role of the hub genes in intervertebral disc degeneration and providing new clues for potential disease mechanisms and treatment strategies.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40289127", "locator": "sections[6] \"Mendelian randomization analysis\" paragraph 2", "quote": "We used Mendelian randomization methods to provide more reliable causal inference, thereby clarifying the role of the hub genes in intervertebral disc degeneration and providing new clues for potential disease mechanisms and treatment strategies."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data is provided within the manuscript or supplementary information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40289127", "locator": "sections[35] \"Data availability\" paragraph 2", "quote": "Data is provided within the manuscript or supplementary information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified four differentially expressed hub genes, COL6A2, DCXR, GLRX, and PDGFRB, through bioinformatics methods.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40289127", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of 126 differentially expressed genes were identified in the GEO database, and 4 differentially expressed hub genes (COL6A2, DCXR, GLRX, and PDGFRB) were identified through bioinformatics methods."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified four differentially expressed hub genes, COL6A2, DCXR, GLRX, and PDGFRB, through bioinformatics methods.", "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:40289127"], "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:GSE186542"], "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:GSE186542"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40289127", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-025-98070-4", "sha256": 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"asset:data:geo:GSE245147 not downloaded", "asset:data:geo:GSE245147 licence not read", "asset:data:geo:GSE70362 not downloaded", "asset:data:geo:GSE70362 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "genetic_association", "specific": "mendelian_randomisation", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["mr_estimate"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We used Mendelian randomization methods to provide more reliable causal inference, thereby clarifying the role of the hub genes in intervertebral disc degeneration and providing new clues for potential disease mechanisms and treatment strategies."}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", 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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": ["GSE70362", "GSE186542", "GSE245147"], "resolved_accessions": ["GSE70362", "GSE186542", "GSE245147"], "statements": ["Data is provided within the manuscript or supplementary information files."], "basis": "The paper names GSE70362, GSE186542, GSE245147 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": ["mr_estimate"], "assets": ["source:pmid:40289127", "data:geo:GSE186542"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE186542"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:51:12Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16918, "completion_tokens": 2439, "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:40289127", "type": "paper", "label": "pmid:40289127"}, {"id": "source:pmid:40289127", "type": "manuscript", "label": "PMID 40289127 full text"}, {"id": "data:geo:GSE186542", "type": "dataset", "label": "GEO GSE186542"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40289127", "type": "paper", "label": "pmid:40289127"}, {"id": "source:pmid:40289127", "type": "manuscript", "label": "PMID 40289127 full text"}, {"id": "data:geo:GSE186542", "type": "dataset", "label": "GEO GSE186542"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40289127", "type": "extraction", "used": ["source:pmid:40289127"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE186542", "type": "accession_resolution", "used": ["data:geo:GSE186542"], "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:40289127", "parent_hash": "sha256:11c4648afc8672595e1eaf9593cd1b139edea541830e446941495991a0be6666", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE186542 licence not read", "asset:data:geo:GSE186542 not downloaded", "asset:data:geo:GSE245147 licence not read", "asset:data:geo:GSE245147 not downloaded", "asset:data:geo:GSE70362 licence not read", "asset:data:geo:GSE70362 not downloaded", "execution.not_run", "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": ["d 10 healthy disc tissue samples, and the RT‒qPCR results were consistent with the bioinformat", "was tested by molecular docking technology. Real-time quantitative PCR was used to confirm the expression of key ge"], "order_basis": "paper_text_order:1442", "id": "assay:1"}, {"role": "analysis", "definition_id": "genetic_association", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["mr_estimate"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We used Mendelian randomization methods to provide more reliable causal inference, thereby clarifying the role of the hub genes in intervertebral disc degeneration and providing new clues for potential disease mechanisms and treatment strategies."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]},"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":"2026-11-04T04:17:08+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}}}