{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40524719", "kind": "science-record", "revision": 3, "content_hash": "sha256:d63d858ccd0fa4b3003fffd939701d924ae8ed1a174021d62625cee335f7d1cc", "created_at": "2026-11-01T20:30:37Z", "updated_at": "2026-11-01T22:14:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD.", "doi": "10.2147/COPD.S511696", "pmid": "40524719", "authors": ["Jiale Zhao", "Xiahui Ge", "Hailong Li", "Genfei Jing", "Weirong Ma", "Yuchun Fan", "Juan Chen", "Zhijun Zhao", "Jia Hou"], "journal": "International journal of chronic obstructive pulmonary disease", "year": 2025, "abstract": "Background: Chronic Obstructive Pulmonary Disease (COPD), a complex respiratory disorder, results from genetic and environmental factors. Uncovering its genetic basis is vital for diagnostics and treatment. Robust genetic analysis is essential to establish a causal link.\nMethods: Genome-wide DNA methylation analysis was performed using the Illumina Infinium HumanMethylation850 BeadChip in peripheral blood from 8 COPD patients and 8 healthy smoking controls. Differentially methylated genes (DMGs) were cross-analyzed with differentially expressed genes (DEGs) identified from the Gene Expression Omnibus (GEO) dataset GSE38974 (23 COPD, 9 controls). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) networks were utilized to identify COPD-associated hub genes. Mendelian randomization (MR) analysis examined the causal relationship between hub genes and COPD. The expression of selected hub genes was validated through RT-qPCR (80 COPD, 62 controls), immunohistochemistry, and Western blot analyses (10 COPD and 10 controls).\nResults: We found 10,593 DMGs and 646 DEGs associated with COPD. These genes were compared with WGCNA module genes, and the Protein-Protein Interaction (PPI) network interaction diagram was drawn, thereby identifying five Hub genes: PPIB, HSPA2, PRPF19, FKBP10 and DOHH. The expression levels of DOHH, FKBP10, PPIB and PRPF19 are higher in COPD, while the expression level of HSPA2 is lower. MR results indicate a potential causal relationship between PRPF19, PPIB and COPD. RT-qPCR, immunohistochemistry and Western blot experiments verified that the expression of PRPF-19 and PPIB was up-regulated in peripheral blood and lung tissue, which was consistent with the results of bioinformatics analysis.\nConclusion: Our findings suggest that PRPF19 and PPIB may serve as promising diagnostic biomarkers in COPD. Further studies are required to fully elucidate their roles in COPD pathogenesis.", "claims": [{"id": "claim-method", "statement": "The R package “WGCNA”18 was applied to find COPD-related modules and genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40524719", "locator": "sections[7] \"Weighted Gene Co-Expression Network Construction and Analysis\" paragraph 2", "quote": "The R package “WGCNA”18 was applied to find COPD-related modules and genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data and materials are available upon request by contacting the correspondence author Jia Hou (houj@live.com).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40524719", "locator": "sections[29] \"Data Sharing Statement\" paragraph 2", "quote": "Data and materials are available upon request by contacting the correspondence author Jia Hou (houj@live.com)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "PRPF19 and PPIB may serve as promising diagnostic biomarkers in COPD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40524719", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our findings suggest that PRPF19 and PPIB may serve as promising diagnostic biomarkers in COPD."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "PRPF19 and PPIB may serve as promising diagnostic biomarkers in COPD.", "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:40524719"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"p_value": "sing the Wilcoxon test (p-value < 0"}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon", "step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40524719", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/COPD.S511696", "sha256": "sha256:9f87cbc127a8ef95bb9537aa6010cdaafb4d12916bd158bb0ff6a339b815d592", "bytes": 42522, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/COPD.S511696", "version": null, "note": "Full article fetched from PMC; 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RT-qPCR, immunohistochemistry and Western blot exper", "selected hub genes was validated through RT-qPCR (80 COPD, 62 controls), immunohistochemistry", "lationship between PRPF19, PPIB and COPD. RT-qPCR, immunohistochemistry and Western blot exper"], "order_basis": "paper_text_order:1001", "id": "assay:1"}, {"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": ["ated through RT-qPCR (80 COPD, 62 controls), immunohistochemistry, and Western blot analyses (10 COPD and 10 c", "ship between PRPF19, PPIB and COPD. RT-qPCR, immunohistochemistry and Western blot experiments verified that t", "tion experiments, including Western blot and immunohistochemistry analyses, to verify the protein expression o"], "order_basis": "paper_text_order:1032", "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": 0.99, "evidence": ["OPD, 62 controls), immunohistochemistry, and Western blot analyses (10 COPD and 10 controls). Results:", "and COPD. RT-qPCR, immunohistochemistry and Western blot experiments verified that the expression of", "ilized for validation experiments, including Western blot and immunohistochemistry analyses, to verify", "H, FKBP10, PPIB, and PRPF19 (Figure S4B- F). Western Blot Analysis of PRPF19, PPIB, and Apoptosis-Rela"], "order_basis": "paper_text_order:1058", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": [". Western Blot Analysis of PRPF19, PPIB, and Apoptosis-Related Proteins in COPD Lung Tissues Wester", "(Figure 7A and B). Moreover, the analysis of apoptosis-related proteins demonstrated increased expr", "ated in COPD but may also be associated with apoptosis regulation, as indicated by the shift toward", "PRPF19 and PPIB Expression and Their Role in Apoptosis Regulation in COPD Lung Tissues. (A) Represe"], "order_basis": "paper_text_order:8766", "id": "assay:4"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "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. 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