{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33178205", "kind": "science-record", "revision": 8, "content_hash": "sha256:5cbc1a4070bc5eb3427e787f48fd4f429a8a54708b27e4b91d98484d1f3ffeb8", "created_at": "2026-11-01T15:41:15Z", "updated_at": "2026-11-01T22:45:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Posttranscriptional Gene Regulatory Networks in Chronic Airway Inflammatory Diseases: In silico Mapping of RNA-Binding Protein Expression in Airway Epithelium.", "doi": "10.3389/fimmu.2020.579889", "pmid": "33178205", "authors": ["Luca Ricciardi", "Giorgio Giurato", "Domenico Memoli", "Mariagrazia Pietrafesa", "Jessica Dal Col", "Ilaria Salvato", "Annunziata Nigro", "Alessandro Vatrella", "Gaetano Caramori", "Vincenzo Casolaro", "Cristiana Stellato"], "journal": "Frontiers in immunology", "year": 2020, "abstract": "Background: Posttranscriptional gene regulation (PTGR) contributes to inflammation through alterations in messenger RNA (mRNA) turnover and translation rates. RNA-binding proteins (RBPs) coordinate these processes but their role in lung inflammatory diseases is ill-defined. We evaluated the expression of a curated list of mRNA-binding RBPs (mRBPs) in selected Gene Expression Omnibus (GEO) transcriptomic databases of airway epithelium isolated from chronic obstructive pulmonary disease (COPD), severe asthma (SA) and matched control subjects, hypothesizing that global changes in mRBPs expression could be used to infer their pathogenetic roles and identify novel disease-related regulatory networks. Methods: A published list of 692 mRBPs [Nat Rev Genet 2014] was searched in GEO datasets originated from bronchial brushings of stable COPD patients (C), smokers (S), non-smokers (NS) controls with normal lung function (n = 6/12/12) (GEO ID: GSE5058) and of (SA) and healthy control (HC) (n = 6/12) (GSE63142). Fluorescence intensity data were extracted and normalized on the medians for fold change (FC) comparisons. FCs were set at ≥ |1.5| with a false discovery rate (FDR) of ≤ 0.05. Pearson correlation maps and heatmaps were generated using tMEV tools v4_9_0.45. DNA sequence motifs were searched using PScan-ChIP. Gene Ontology (GO) was performed with Ingenuity Pathway Analysis (IPA) tool. Results: Significant mRBP expression changes were detected for S/NS, COPD/NS and COPD/S (n = 41, 391, 382, respectively). Of those, 32% of genes changed by FC ≥ |1.5| in S/NS but more than 60% in COPD/NS and COPD/S (n = 13, 267, 257, respectively). Genes were predominantly downregulated in COPD/NS (n = 194, 73%) and COPD/S (n = 202, 79%), less so in S/NS (n = 4, 31%). Unsupervised cluster analysis identified in 4 out of 12 S the same mRBP pattern seen in C, postulating subclinical COPD. Significant DNA motifs enrichment for transcriptional regulation was found for downregulated RBPs. Correlation analysis identified five clusters of co-expressed mRBPs. GO analysis revealed significant enrichments in canonical pathways both specific and shared among comparisons. Unexpectedly, no significant mRBPs modulation was found in SA compared to controls. Conclusions: Airway epithelial mRBPs profiling reveals a COPD-specific global downregulation of RBPs shared by a subset of control smokers, the potential of functional cooperation by coexpressed RBPs and significant impact on relevant pathogenetic pathways in COPD. Elucidation of PTGR in COPD could identify disease biomarkers or pathways for therapeutic targeting.", "claims": [{"id": "claim-method", "statement": "The significance values for the canonical pathways is calculated by Fisher's exact test right-tailed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33178205", "locator": "sections[4] \"Gene Ontology (GO)\" paragraph 2", "quote": "The significance values for the canonical pathways is calculated by Fisher's exact test right-tailed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33178205", "locator": "sections[10] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33178205"], "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:GSE5058"], "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:GSE5058"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33178205", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2020.579889", "sha256": "sha256:5c32f09d1cb2ff11f4ff497f5f88f2250461f955437683b2c441d1d660aed8ce", "bytes": 44643, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2020.579889", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7596416", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE5058", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5058", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE5058", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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S", "FCCOPD VS. NS", "Main functions", "References"], ["FUS", "FUS RNA binding protein", "−34.63", "−37.5", "Involved in pre-mRNA splicing and the export of fully processed mRNA to the cytoplasm", "(28)"], ["", "", "", "", "Maintenance of genomic integrity and mRNA/microRNA processing", "(29)"], ["THRAP3", "Thyroid hormon receptor associated protein 3", "−33.54", "−31.58", "Enhances the transcriptional activation mediated by PPARG cooperatively with HELZ2", "(30)"], ["", "", "", "", "Acts as a coactivator of the CLOCK-ARNTL heterodimer", "(31)"], ["", "", "", "", "Involved in response to DNA damage", "(30)"], ["DDX17", "DEAD-Box helicase 17", "−31.04", "−46.27", "RNA helicase", "(32)"], ["", "", "", "", "pre-mRNA splicing, alternative splicing, ribosomal RNA processing and miRNA processing, transcription regulation", "(33–36)"], ["", "", "", "", "Splicing of mediators of steroid hormone signaling pathway", "(37)"], ["", "", "", "", "Synergizes with TP53 in the activation of the MDM2 promoter; may also coactivate MDM2 transcription through a TP53-independent pathway", "(38–40)"], ["", "", "", "", "Coregulates SMAD-dependent transcriptional activity during epithelial-to-mesenchymal transition", "(35)"], ["", "", "", "", "Plays a role in estrogen and testosterone signaling pathway", "(37, 39–41)"], ["", "", "", "", "Promotes mRNA degradation mediated by the antiviral zinc-finger protein ZC3HAV1", "(42)"], ["SCAF11", "SR-Related CTD associated factor 11", "−14.4", "−12.7", "Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly", "(43)"], ["STRAP", "Serine/threonine kinase receptor associated protein", "−10.8", "−8.22", "Plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome", "(44)"], ["", "", "", "", "Negatively regulates TGFβ signaling", "(44)"], ["", "", "", "", "Positively regulates the PDPK1 kinase activity", "(44)"], ["RBM14", "RNA binding motif protein 14", "−7.36", "−6.31", "General nuclear coactivator, and an RNA splicing modulator. Isoform 1 may function as a nuclear receptor coactivator. Isoform 2, functions as a transcriptional repressor", "(45)"], ["", "", "", "", "Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation", "(46)"], ["BCLAF1", "Bcl-2-associated transcription factor 1", "−7.32", "−4.13", "Regulation of apoptosis interacting with BCL2 proteins", "(47)"], ["ILF3", "Interleukin enhancer binding factor 3", "−6.33", "−4.61", "Forms a heterodimer with ILF2, required for T-cell expression of IL-2", "(44)"], ["", "", "", "", "Post transcriptional regulation of mRNA binding to poly-U elements and AU-rich elements (AREs) in the 3′-UTR of target mRNA", "(48)"], ["", "", "", "", "Participates in the innate antiviral response", "(49, 50)"], ["", "", "", "", "Plays an essential role in the biogenesis of circRNAs", "(50)"], ["SFSWAP", "Splicing factor SWAP", "−5.81", "−3.34", "Regulates the splicing of fibronectin and CD45 genes", "(51)"], ["RBM25", "RNA binding motif protein 25", "−5.7", "−4.16", "Regulator of alternative pre-mRNA splicing", "(52)"], ["", "", "", "", "Involved in apoptotic cell death through the regulation of the apoptotic factor BCL2L1 (proapoptotic isoform S, antiapoptotic isoform L)", "(52)"], ["DHX36", "DEAH-Box helicase 36", "−4.96", "−5.31", "Enhance the deadenylation and decay of mRNAs with 3′-UTR AU-rich elements (ARE-mRNA)", "(53)"], ["", "", "", "", "Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures", "(54–57)"], ["", "", "", "", "Plays a role in genomic integrity. Converts the G4-RNA structure present in TREC into a double-stranded RNA", "(56, 58–62)"], ["", "", "", "", "Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability", "(63, 64)"], ["", "", "", "", "Plays a role in transcriptional regulation and post-transcriptional regulation", "(54, 65, 66)"], ["HNRNPA2B1", "Heterogeneous nuclear ribonucleoprotein A2/B1", "−4.91", "−4.63", "Associates with nascent pre-mRNAs, packaging them into hnRNP particles and drive them into transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs.", "(67)"], ["", "", "", "", "Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons recognizing binding the A2RE or the A2RE11 sequence motifs present on some mRNAs.", "(68)"], ["", "", "", "", "Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion", "(69)"], ["", "", "", "", "Involved in the transport of HIV-1 genomic RNA out of the nucleus, to the MTOC, and then from the MTOC to the cytoplasm: acts by specifically recognizing and binding the A2RE sequence motifs present on HIV-1 genomic RNA.", "(69)"], ["CCAR1", "Cell division cycle and apoptosis regulator 1", "−2.79", "−2.93", "Plays a role in cell cycle progression and/or cell proliferation", "(70, 71)"], ["", "", "", "", "p53 coactivator", "(72)"], ["NR0B1", "Nuclear receptor subfamily 0 Group B member 1", "1.57", "3.31", "Acts as a dominant-negative regulator of transcription which is mediated by the retinoic acid receptor", "(73)"], ["", "", "", "", "Functions as an anti-testis gene by acting antagonistically to Sry", "(73)"], ["", "", "", "", "Plays a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency", "(73)"], ["RBPMS", "RNA-Binding protein with multiple splicing", "1.77", "1.4", "pre-mRNA maturation (binds to poly(A) RNA)", "(74, 75)"], ["", "", "", "", "Required to increase TGFB1/Smad-mediated transactivation", "(75)"], ["HDLBP", "High density lipoprotein binding protein", "1.91", "2.53", "Regulates excess cholesterol levels in cells", "(76)"], ["", "", "", "", "Induces heterochromatin formation", "(76)"], ["MATR3", "Matrin 3", "2", "3.3", "Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3", "(46)"], ["DHX30", "DExH-Box helicase 30", "2.18", "2.45", "Assembly of the mitochondrial large ribosomal subunit", "(77, 78)"], ["", "", "", "", "Required for optimal function of the zinc-finger antiviral protein ZC3HAV1", "(79)"], ["", "", "", "", "Involved in nervous system development differentiation", "(79)"]], "row_count": 49, "column_count": 6, "numeric_cells": 111, "header_rows": 1, "locator": "section[7]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33178205:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:459272df463bc6f7bb4eae54ae108b71c8586f42a1ef49dd72ed71f2b4b58673", "bytes": 3512, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[2]#T2", "version": null, "note": "GO analysis by IPA indicating canonical pathways in which RBP enrichment is significant for each comparison, with predicted functional outcome indicated by z-score (See Methods for details), and RBP molecules involved.", "structure": {"pmcid": "PMC7596416", "section_index": 7, "section_title": "Expression Profile of mRBPs in Airway Epithelial Transcriptomic Database of Patients With Stable COPD Compared to Non-smoker and Smoker Control Subjects", "row_count": 33, "column_count": 5}, "table": {"label": "Table 2", "caption": "GO analysis by IPA indicating canonical pathways in which RBP enrichment is significant for each comparison, with predicted functional outcome indicated by z-score (See Methods for details), and RBP molecules involved.", "rows": [["2A. S/NS"], ["Ingenuity canonical pathways", "p-value", "z-score", "Prediction", "Molecules"], ["Estrogen receptor signaling", "1.38E-05", "−0.44", "Inhibition", "PRKDC,NR0B1,SPEN,POLR2H, POLR2L"], ["Cleavage and polyadenylation of Pre-mRNA", "3.47E-04", "0", "0", "CPSF2,CPSF6"], ["Nucleotide excision repair pathway", "3.02E-03", "−1.41", "Inhibition", "POLR2H,POLR2L"], ["Assembly of RNA polymerase II complex", "6.03E-03", "−1.41", "Inhibition", "POLR2H,POLR2L"], ["NER pathway", "2.19E-02", "−1.41", "Inhibition", "POLR2H,POLR2L"], ["DNA double-strand break repair by non-homologous end joining", "3.24E-02", "1", "Activation", "PRKDC"], ["RAN signaling", "3.63E-02", "1", "Activation", "TNPO1"], ["Granzyme B signaling", "3.63E-02", "1", "Activation", "PRKDC"], ["Androgen signaling", "3.98E-02", "−1.41", "Inhibition", "POLR2H,POLR2L"], ["Hereditary breast cancer signaling", "4.68E-02", "−1.41", "Inhibition", "POLR2H,POLR2L"], ["2B. COPD/NS"], ["Cleavage and polyadenylation of pre-mRNA", "2E-15", "−3.16", "Inhibition", "PAPOLA,CPSF2,CPSF6,CSTF1,NUDT21,CPSF1,CSTF2,CPSF3,CSTF3,CPSF4"], ["Regulation of eIF4 and p70S6K signaling", "2.88E-06", "−3.87", "Inhibition", "EIF2B4,PAIP2,EIF3E,EIF4G1,EIF2B2,EIF4E,EIF3M,EIF3G,EIF1,EIF3B,EIF3A,EIF2B1, EIF3L,EIF1AX,EIF3K"], ["EIF2 signaling", "3.02E-05", "−4", "Inhibition", "EIF2B4,EIF3E,EIF4G1,EIF2B2,EIF4E,EIF3,EIF3G,PTBP1,EIF1,EIF3,HNRNPA1,EIF2B,EIF3A,EIF3L,EIF1AX,EIF3K"], ["Estrogen receptor signaling", "0.000209", "−2.11", "Inhibition", "PRKDC,DDX5,THRAP3,SPEN,NR0B1,POLR2H,GTF2F1,HNRNPD,RBFOX2,POLR2K,POLR2L"], ["Tight junction signaling", "0.000363", "−1.73", "Inhibition", "CPSF2,CPSF6,CSTF1,NUDT21,CPSF1,CSTF2,YBX3,CPSF3,SYMPK,SAFB,CSTF3,CPSF4"], ["Spliceosomal cycle", "0.000501", "1.41", "Activation", "U2AF1/U2AF1L5,U2AF2"], ["Telomere extension by telomerase", "0.004169", "−0.57", "Inhibition", "HNRNPA1,XRCC6,HNRNPA2B1"], ["RAN signaling", "0.005129", "−0.57", "Inhibition", "KPNB1,RANBP2,TNPO1"], ["Assembly of RNA polymerase II complex", "0.025704", "−2", "Inhibition", "POLR2H,GTF2F1,POLR2K,POLR2L"], ["mTOR signaling", "0.038019", "−3", "Inhibition", "EIF3G,EIF3B,EIF3A,EIF3E,EIF4G1,EIF4E,EIF3L,EIF3M,EIF3K"], ["2C. COPD/S"], ["Regulation of eIF4 and p70S6K signaling", "5.75E-08", "0.24", "Activation", "EIF2B4,EIF4G3,PAIP2,EIF3E,EIF4G1,EIF2B2,EIF4E,EIF3M,EIF3G,EIF1,EIF3B,PAIP1,EIF3A,EIF2B5,EIF1AX,EIF3L,EIF3K"], ["EIF2 signaling", "2.24E-07", "0.22", "Activation", "EIF2B4,EIF4G3,EIF3E,EIF4G1,EIF2B2,EIF4E,EIF3M,EIF3G,PTBP1,EIF1,EIF3B,HNRNPA1,EIF5,PAIP1,EIF3A,EIF2B5,EIF1AX,EIF3,EIF3K"], ["RAN signaling", "6.46E-07", "−1.63", "Inhibition", "KPNB1,RANBP2,TNPO1,RAN,XPO1,IPO5"], ["Cleavage and polyadenylation of pre-mRNA", "3.16E-06", "−1.34", "Inhibition", "PAPOLA,CPSF2,CSTF1,NUDT21,CSTF3"], ["Spliceosomal cycle", "0.000468", "0", "0", "U2AF1/U2AF1L5,U2AF2"], ["Oxidized GTP and dGTP detoxification", "0.00138", "0", "0", "DDX6,RUVBL2"], ["mTOR signaling", "0.004365", "−0.30", "Inhibition", "EIF3G,EIF3B,EIF3A,EIF4G3,EIF3,EIF4G1,EIF3L,EIF4E,EIF3M,EIF4B,EIF3K"], ["Estrogen receptor signaling", "0.008318", "−1.41", "Inhibition", "PRKDC,THRAP3,NR0B1,SPEN,HNRNPD,GTF2F1,POLR2K,POLR2"], ["Telomere extension by telomerase", "0.040738", "−1.41", "Inhibition", "HNRNPA1,HNRNPA2B1"]], "row_count": 33, "column_count": 5, "numeric_cells": 69, "header_rows": 2, "locator": "section[7]/table-wrap[2]#T2"}}, {"id": "asset:table:pmid:33178205:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4789586d7cd2882b4f1b4b2bcdf0cd3b098759b3558aca2d221a5fdf38d120d4", "bytes": 1435, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[3]#T3", "version": null, "note": "Canonical Pathways identified by IPA analysis of mRBPs clusters 1 to 5 as shown in Figure 7.", "structure": {"pmcid": "PMC7596416", "section_index": 7, "section_title": "Expression Profile of mRBPs in Airway Epithelial Transcriptomic Database of Patients With Stable COPD Compared to Non-smoker and Smoker Control Subjects", "row_count": 23, "column_count": 3}, "table": {"label": "Table 3", "caption": "Canonical Pathways identified by IPA analysis of mRBPs clusters 1 to 5 as shown in Figure 7.", "rows": [["Ingenuity canonical pathways"], ["Cluster 1", "p-value", "Molecules"], ["RAN signaling", "2.24E-02", "TNPO1"], ["Apelin muscle signaling pathway", "2.51E-02", "TFAM"], ["Cluster 2", "p-value", "Molecules"], ["RAN Signaling", "1.20E-02", "RANBP2"], ["Pyrimidine ribonucleotides interconversion", "2.95E-02", "DDX3X"], ["Pyrimidine ribonucleotides de novo biosynthesis", "3.09E-02", "DDX3X"], ["Cluster 3", "p-value", "Molecules"], ["Telomere extension by telomerase", "3.24E-04", "HNRNPA1,HNRNPA2B1"], ["RAN signaling", "4.17E-04", "RANBP2,TNPO1"], ["IL-15 production", "2.00E-02", "CLK1,CLK4"], ["Cluster 4", "p-value", "Molecules"], ["RAN signaling", "1.48E-05", "RANBP2,TNPO1,XPO1"], ["Telomere extension by telomerase", "8.32E-04", "HNRNPA1,HNRNPA2B1"], ["Cleavage and polyadenylation of pre-mRNA", "3.39E-02", "NUDT21"], ["IL-15 production", "4.68E-02", "CLK1,CLK4"], ["Inhibition of ARE-Mediated mRNA degradation pathway", "4.79E-02", "DCP2,TIA1"], ["Cluster 5", "p-value", "Molecules"], ["Telomere extension by telomerase", "3.31E-04", "HNRNPA1,HNRNPA2B1"], ["Ran signaling", "4.27E-04", "RANBP2,XPO1"], ["Inhibition of ARE-mediated mRNA degradation pathway", "2.04E-02", "DCP2,TIA1"], ["Cleavage and polyadenylation of pre-mRNA", "2.14E-02", "NUDT21"]], "row_count": 23, "column_count": 3, "numeric_cells": 26, "header_rows": 1, "locator": "section[7]/table-wrap[3]#T3"}}], "gaps": ["asset:data:geo:GSE5058 not downloaded", "asset:data:geo:GSE5058 licence not read", "asset:data:geo:GSE63142 not downloaded", "asset:data:geo:GSE63142 licence not read", "asset:data:geo:GSE8545 not downloaded", "asset:data:geo:GSE8545 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "contingency_analysis", "specific": "fisher_exact", "label": "Categorical (contingency table) analysis", "dsl_operations": ["contingency_table", "chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The significance values for the canonical pathways is calculated by Fisher's exact test right-tailed."}}, {"id": "method-2", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pearson correlation"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["contingency_table", "chi_square_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: fisher_exact."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE5058", "GSE63142", "GSE8545"], "resolved_accessions": ["GSE5058", "GSE63142", "GSE8545"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."], "basis": "The paper names GSE5058, GSE63142, GSE8545 in Gene Expression Omnibus (GEO) public repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["contingency_table", "chi_square_test"], "assets": ["source:pmid:33178205", "data:geo:GSE5058", "asset:table:pmid:33178205:1", "asset:table:pmid:33178205:2", "asset:table:pmid:33178205:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE5058"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:24:04Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 30650, "completion_tokens": 1875, "cached_tokens": 10248}}, "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:33178205", "type": "paper", "label": "pmid:33178205"}, {"id": "source:pmid:33178205", "type": "manuscript", "label": "PMID 33178205 full text"}, {"id": "data:geo:GSE5058", "type": "dataset", "label": "GEO GSE5058"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33178205", "type": "paper", "label": "pmid:33178205"}, {"id": "source:pmid:33178205", "type": "manuscript", "label": "PMID 33178205 full text"}, {"id": "data:geo:GSE5058", "type": "dataset", "label": "GEO GSE5058"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33178205", "type": "extraction", "used": ["source:pmid:33178205"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE5058", "type": "accession_resolution", "used": ["data:geo:GSE5058"], "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:33178205", "parent_hash": "sha256:f4c12c7461250c82f018d8caef830b3072466b86db2ce2f0d867415cbc5413c2", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE5058 licence not read", "asset:data:geo:GSE5058 not downloaded", "asset:data:geo:GSE63142 licence not read", "asset:data:geo:GSE63142 not downloaded", "asset:data:geo:GSE8545 licence not read", "asset:data:geo:GSE8545 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": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rmed using Agilent-014850 Whole Human Genome Microarray 4x44K G4112F. Fluorescence intensity data fr", "anges in disease state vs. controls (C). The Affymetrix Human Genome U133 Plus 2.0 Array platform wa"], "order_basis": "paper_text_order:4814", "id": "assay:1"}, {"role": "analysis", "definition_id": "contingency_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["contingency_table", "chi_square_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The significance values for the canonical pathways is calculated by Fisher's exact test right-tailed."], "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":"2026-11-04T03:04:34+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}}}