{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40594234", "kind": "science-record", "revision": 3, "content_hash": "sha256:07ef7493ae87d3eecbe2318fed3b6460ac2e6d87ce9c12ca999c9d0cf7c2f3a4", "created_at": "2026-11-01T20:30:40Z", "updated_at": "2026-11-01T22:14:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson's disease.", "doi": "10.1038/s41598-025-05580-2", "pmid": "40594234", "authors": ["Dongdong Chen", "Qingqing Huang", "Ming Ye"], "journal": "Scientific reports", "year": 2025, "abstract": "There is a close relationship between Parkinson's disease (PD) and circadian rhythm disturbances. To investigate genes linked to circadian rhythm disruption in PD, we analyzed the PD dataset via bioinformatic techniques. We downloaded 2 datasets from the GEO database; one dataset (GSE20163) was used as an internal training set, whereas the other dataset (GSE20164) was used as an external set. We first performed differential gene expression analysis on the GSE20163 dataset to identify differentially expressed genes (DEGs). We then conducted weighted gene co-expression network analysis on this dataset to select the most significant modules (turquoise modules) and took the intersection of the two to obtain crossover genes (85 genes), which were functionally enriched in the Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). These 85 crossover genes were again taken to intersect with circadian rhythm-related genes (2531) to form circadian rhythm-related genes (16). Box plot presentation was performed and found that all p-values were significant. Least absolute shrinkage and selection operator (LASSO) regression analysis was carried out to find 2 representative genes (CDK5, BSCL2). ROC curve analysis was conducted in both the cohort and the validation set, demonstrating statistically significant in each group. Gene set enrichment analysis (GSEA) was conducted on these 2 genes in the internal training set. Analysis of these two genes revealed that they are involved in the regulation of biological processes and synaptic signaling. The diagnostic and predictive model for Parkinson's disease (PD), which relies on circadian-related genes (BSCL2 and CDK5), has excellent diagnostic and predictive performance. This model could serve as a valuable device in the diagnosis of circadian disturbance in PD. Finally, immunohistochemistry and immunoblotting-related experiments were performed for further confirmation. Immunoblot analysis revealed decreased protein levels of BSCL2 and CDK5 in the PD group. Immunohistochemistry further demonstrated reduced TH-positive neuron counts in this experimental cohort. Taking these findings together, BSCL2 and CDK5 are important genes associated with circadian rhythm disturbance in PD.", "claims": [{"id": "claim-method", "statement": "Sixteen intersecting genes related to circadian rhythms were obtained for further analysis. For further screening, the LASSO machine learning method was selected.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40594234", "locator": "sections[22] \"LASSO regression algorithm for screening key genes\" paragraph 2", "quote": "Sixteen intersecting genes related to circadian rhythms were obtained for further analysis. For further screening, the LASSO machine learning method was selected."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40594234", "locator": "sections[36] \"notes\" paragraph 1", "quote": "Data are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The 16 intersecting genes were further screened using least absolute shrinkage and selection operator (LASSO) regression (Fig. 7a, b), resulting in 2 differential genes: CDK5 and BSCL2.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40594234", "locator": "sections[9] \"Screening for differential genes associated with circadian rhythm disorders by LASSO regression\" paragraph 2", "quote": "The 16 intersecting genes were further screened using least absolute shrinkage and selection operator (LASSO) regression (Fig. 7a, b), resulting in 2 differential genes: CDK5 and BSCL2."}, {"asset": "source:pmid:40594234", "locator": "sections[9] \"Screening for differential genes associated with circadian rhythm disorders by LASSO regression\" paragraph 2", "quote": "Further validation using ROC curves was performed in both the test (AUC for CDK5 0.861, AUC for BSCL2 0.889) and validation sets (AUC for CDK5 0.80, AUC for BSCL2 0.867), and both were found to be significant (Fig. 7e:h)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The 16 intersecting genes were further screened using least absolute shrinkage and selection operator (LASSO) regression (Fig. 7a, b), resulting in 2 differential genes: CDK5 and BSCL2.", "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:40594234"], "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:GSE20163"], "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:GSE20163"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40594234", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-025-05580-2", "sha256": "sha256:35b4ec23381dfdb225b0fa0ecf5212a934d7cec6c0ba99a12ef0dd50f26c1846", "bytes": 34366, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-025-05580-2", "version": null, "note": "Full article fetched from PMC; 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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": ["GSE20163", "GSE20164"], "resolved_accessions": ["GSE20163", "GSE20164"], "statements": ["Data are available from the corresponding author on reasonable request."], "basis": "The paper names GSE20163, GSE20164 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "assets": ["source:pmid:40594234", "data:geo:GSE20163"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE20163"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:55:32Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9346, "completion_tokens": 1932, "cached_tokens": 256}}, "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:40594234", "type": "paper", "label": "pmid:40594234"}, {"id": "source:pmid:40594234", "type": "manuscript", "label": "PMID 40594234 full text"}, {"id": "data:geo:GSE20163", "type": "dataset", "label": "GEO GSE20163"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40594234", "type": "paper", "label": "pmid:40594234"}, {"id": "source:pmid:40594234", "type": "manuscript", "label": "PMID 40594234 full text"}, {"id": "data:geo:GSE20163", "type": "dataset", "label": "GEO GSE20163"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40594234", "type": "extraction", "used": ["source:pmid:40594234"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE20163", "type": "accession_resolution", "used": ["data:geo:GSE20163"], "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:40594234", "parent_hash": "sha256:0f556dc50553278bebb83b822960e5e9db8b30c259da679ab1a5259904ed2a80", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE20163 licence not read", "asset:data:geo:GSE20163 not downloaded", "asset:data:geo:GSE20164 licence not read", "asset:data:geo:GSE20164 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["sis of circadian disturbance in PD. Finally, immunohistochemistry and immunoblotting-related experiments were", "in levels of BSCL2 and CDK5 in the PD group. Immunohistochemistry further demonstrated reduced TH-positive neu"], "order_basis": "paper_text_order:1925", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nce in PD. Finally, immunohistochemistry and immunoblotting-related experiments were performed for furth", "nts were performed for further confirmation. Immunoblot analysis revealed decreased protein levels o"], "order_basis": "paper_text_order:1950", "id": "assay:2"}, {"role": "analysis", "definition_id": "diagnostic_evaluation", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["ROC curve"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]},"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":"2026-11-04T00:44:41+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}}}