{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30091044", "kind": "science-record", "revision": 8, "content_hash": "sha256:b4fa7f173b06b3dbfd3146ca59f641ca6b0459c27a6baa7759be908344a09014", "created_at": "2026-11-01T15:40:36Z", "updated_at": "2026-11-01T22:43:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Human fetoplacental arterial and venous endothelial cells are differentially programmed by gestational diabetes mellitus, resulting in cell-specific barrier function changes.", "doi": "10.1007/s00125-018-4699-7", "pmid": "30091044", "authors": ["Silvija Cvitic", "Boris Novakovic", "Lavinia Gordon", "Christine M Ulz", "Magdalena Mühlberger", "Francisca I Diaz-Perez", "Jihoon E Joo", "Vendula Svendova", "Michael G Schimek", "Slave Trajanoski", "Richard Saffery", "Gernot Desoye", "Ursula Hiden"], "journal": "Diabetologia", "year": 2018, "abstract": "AIMS/HYPOTHESIS: An adverse intrauterine environment can result in permanent changes in the physiology of the offspring and predispose to diseases in adulthood. One such exposure, gestational diabetes mellitus (GDM), has been linked to development of metabolic disorders and cardiovascular disease in offspring. Epigenetic variation, including DNA methylation, is recognised as a leading mechanism underpinning fetal programming and we hypothesised that this plays a key role in fetoplacental endothelial dysfunction following exposure to GDM. Thus, we conducted a pilot epigenetic study to analyse concordant DNA methylation and gene expression changes in GDM-exposed fetoplacental endothelial cells.\nMETHODS: Genome-wide methylation analysis of primary fetoplacental arterial endothelial cells (AEC) and venous endothelial cells (VEC) from healthy pregnancies and GDM-complicated pregnancies in parallel with transcriptome analysis identified methylation and expression changes. Most-affected pathways and functions were identified by Ingenuity Pathway Analysis and validated using functional assays.\nRESULTS: Transcriptome and methylation analyses identified variation in gene expression linked to GDM-associated DNA methylation in 408 genes in AEC and 159 genes in VEC, implying a direct functional link. Pathway analysis found that genes altered by exposure to GDM clustered to functions associated with 'cell morphology' and 'cellular movement' in healthy AEC and VEC. Further functional analysis demonstrated that GDM-exposed cells had altered actin organisation and barrier function.\nCONCLUSIONS/INTERPRETATION: Our data indicate that exposure to GDM programs atypical morphology and barrier function in fetoplacental endothelial cells by DNA methylation and gene expression change. The effects differ between AEC and VEC, indicating a stringent cell-specific sensitivity to adverse exposures associated with developmental programming in utero.\nDATA AVAILABILITY: DNA methylation and gene expression datasets generated and analysed during the current study are available at the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo ) under accession numbers GSE106099 and GSE103552, respectively.", "claims": [{"id": "claim-method", "statement": "The limma package [21] was used to fit a linear model to compare dAEC and dVEC vs control samples, with patient as random effect and allowing for batch effects.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30091044", "locator": "sections[5] \"DNA methylation analysis\" paragraph 2", "quote": "The limma package [21] was used to fit a linear model to compare dAEC and dVEC vs control samples, with patient as random effect and allowing for batch effects."}], "state": "complete"}, {"id": "claim-data-access", "statement": "DNA methylation and gene expression datasets generated and analysed during the current study are available at the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo) under accession numbers GSE106099 and GSE103552, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30091044", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "DNA methylation and gene expression datasets generated and analysed during the current study are available at the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo) under accession numbers GSE106099 and GSE103552, respectively."}], "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:30091044"], "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:GSE103552"], "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:GSE103552"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30091044", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s00125-018-4699-7", "sha256": 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for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo) under accession numbers GSE106099 and GSE103552, respectively.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "DNA methylation and gene expression datasets generated and analysed during the current study are available at the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo) under accession numbers GSE106099 and GSE103552, respectively.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2773477", "GSM2773478", "GSM2773479", "GSM2773480", "GSM2773481", "GSM2773482", "GSM2773483", "GSM2773484", "GSM2773485", "GSM2773486", "GSM2773487", "GSM2773488", "GSM2773489", "GSM2773490", "GSM2773491", "GSM2773492", "GSM2773493", "GSM2773494", "GSM2773495", "GSM2773496", "GSM2773497", "GSM2773498", "GSM2773499", "GSM2773500", 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"version": null, "note": "DNA methylation and gene expression datasets generated and analysed during the current study are available at the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo) under accession numbers GSE106099 and GSE103552, respectively.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "DNA methylation and gene expression datasets generated and analysed during the current study are available at the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo) under accession numbers GSE106099 and GSE103552, respectively.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2829677", "GSM2829678", "GSM2829679", "GSM2829680", "GSM2829681", "GSM2829682", "GSM2829683", "GSM2829684", "GSM2829685", "GSM2829686", "GSM2829687", "GSM2829688", "GSM2829689", 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"read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#Tab1", "version": null, "note": "Maternal, neonatal and placental clinical variables for gene expression and DNA methylation analyses", "structure": {"pmcid": "PMC6182654", "section_index": 3, "section_title": "Sample collection", "row_count": 32, "column_count": 5}, "table": {"label": "Table 1", "caption": "Maternal, neonatal and placental clinical variables for gene expression and DNA methylation analyses", "rows": [["Variable", "Gene expression", "DNA methylation"], ["", "Normal pregnancy", "GDM pregnancy", "Normal pregnancy", "GDM pregnancy"], ["Maternal data"], ["No. of individuals used for cell isolation", "8", "14", "9", "9"], ["No. of cell isolations (AEC/VEC)", "8/8", "10/11", "9/9", "9/5"], ["Age (years)", "34.0 ± 7.3", "32.8 ± 7.9", "28.4 ± 6.3", "32.7 ± 6.6"], ["Gestational age (weeks)", "39.6 ± 1.5", "38.9 ± 1.2", "40.8 ± 1.5", "39.2 ± 1.3*"], ["Height (m)", "1.66 ± 0.09", "1.66 ± 0.06", "1.70 ± 0.04", "1.70 ± 0.05"], ["Weight before pregnancy (kg)", "77.3 ± 17.5", "83.0 ± 16.6", "75.0 ± 11.6", "83.6 ± 18.5"], ["BMI before pregnancy", "27.7 ± 3.8", "30.1 ± 5.6", "25.8 ± 3.1", "28.6 ± 7.6"], ["Weight before birth (kg)", "92.8 ± 20.0", "95.1 ± 18.1", "90.2 ± 11.5", "94.6 ± 17.6"], ["BMI before birth", "33.3 ± 4.3", "34.8 ± 5.8", "30.1 ± 4.9", "33.0 ± 6.6"], ["Gestational weight gain (kg)", "15.5 ± 4.2", "12.1 ± 9.6", "15.2 ± 2.7", "10.9 ± 10.3"], ["CRP (nmol/l)", "99 ± 87", "56 ± 49*", "92 ± 88", "54 ± 52"], ["HbA1c (mmol/mol)", "ND", "38.8 ± 2.2", "ND", "37.7 ± 2.3"], ["HbA1c (%)", "ND", "5.7 ± 0.2", "ND", "5.6 ± 0.2"], ["OGTT glucose (mmol/l)"], ["Fasting", "4.35 ± 0.44", "5.11 ± 0.42*", "4.35 ± 0.23", "5.56 ± 0.66*"], ["1 h", "6.33 ± 0.96", "10.20 ± 1.91*", "6.23 ± 1.14", "9.32 ± 2.33*"], ["2 h", "5.64 ± 0.63", "7.05 ± 1.45*", "5.33 ± 0.73", "6.35 ± 1.54*"], ["GDM classification (A1/A2)", "", "9/5", "", "4/5"], ["Neonatal data"], ["Male/female ratio", "4/4", "6/8", "4/5", "4/5"], ["Offspring weight (g)", "3547 ± 428", "3275 ± 409", "3443 ± 482", "3318 ± 365"], ["Offspring length (cm)", "51.0 ± 2.1", "50.4 ± 2.0", "50.4 ± 2.7", "50.6 ± 2.7"], ["Placental weight (g)", "515 ± 190", "620 ± 188", "619 ± 195", "595 ± 159"], ["Fetal ponderal index", "26.7 ± 2.0", "25.5 ± 2.2", "26.8 ± 2.6", "25.9 ± 4.6"], ["Fetus/placenta weight ratio", "6.25 ± 1.37", "5.72 ± 1.74", "5.89 ± 1.44", "6.02 ± 1.78"], ["Cord blood insulin (pmol/l)", "ND", "223 ± 269", "150 ± 177", "181 ± 285"], ["Cord blood C-peptide (nmol/l)", "ND", "1.06 ± 0.93", "ND", "0.60 ± 0.23"], ["Cell culture data"], ["Cell isolation passage", "6.1 ± 1.2", "6.6 ± 1.1", "5.4 ± 1.0", "4.8 ± 0.6"]], "row_count": 32, "column_count": 5, "numeric_cells": 97, "header_rows": 2, "locator": "section[3]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:30091044:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": 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maintenance", "6.94 × 10−6 to 3.87 × 10−2", "176"], ["Cellular assembly and organisationb", "2.86 × 10−5 to 3.87 × 10−2", "114"], ["Post-translational modification", "1.54 × 10−4 to 3.77 × 10−2", "26"], ["Cell morphologyb", "2.39 × 10−4 to 4.01 × 10−2", "92"], ["Cellular development", "2.39 × 10−4 to 4.40 × 10−2", "147"], ["VEC"], ["Cellular function and maintenance", "8.24 × 10−4 to 4.91 × 10−2", "53"], ["Molecular transport", "8.24 × 10−4 to 4.91 × 10−2", "51"], ["Cell morphologyb", "9.34 × 10−4 to 4.58 × 10−2", "45"], ["Cell-to-cell signalling and interaction", "9.34 × 10−4 to 4.94 × 10−2", "48"], ["Cellular compromise", "9.34 × 10−4 to 2.89 × 10−2", "14"], ["Gene expression"], ["AEC"], ["Cell cycle", "8.42 × 10−22 to 1.26 × 10−2", "159"], ["Cellular assembly and organisationb", "8.42 × 10−22 to 1.11 × 10−2", "106"], ["DNA replication, recombination and repair", "8.42 × 10−22 to 1.11 × 10−2", "159"], ["Cellular movementb", "2.54 × 10−8 to 1.11 × 10−2", "89"], ["Cellular growth and proliferation", "1.03 × 10−6 to 1.15 × 10−2", "234"], ["VEC"], ["Cell cycle", "1.75 × 10−6 to 1.83 × 10−2", "48"], ["Cell death and survival", "4.96 × 10−5 to 1.36 × 10−2", "25"], ["Cellular assembly and organisationb", "7.46 × 10−5 to 1.67 × 10−2", "46"], ["Cellular function and maintenance", "7.46 × 10−5 to 1.67 × 10−2", "38"], ["DNA replication, recombination and repair", "7.46 × 10−5 to 1.74 × 10−2", "24"]], "row_count": 27, "column_count": 3, "numeric_cells": 40, "header_rows": 1, "locator": "section[14]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:30091044:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2343c4ea870ab49bd4465885fa6a1366df033b9a10f7d35fb4ce1795f6e4ce16", "bytes": 817, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#Tab3", "version": null, "note": "Genes commonly regulated by GDM in AEC and VEC", "structure": {"pmcid": "PMC6182654", "section_index": 17, "section_title": "Concordant DNA methylation and expression changes in fetoplacental AEC and VEC", "row_count": 7, "column_count": 3}, "table": {"label": "Table 3", "caption": "Genes commonly regulated by GDM in AEC and VEC", "rows": [["Gene symbol", "Gene name", "Direction of expression and methylation change"], ["EGFR", "Epidermal growth factor receptor", "Concordant in AEC and VECUpregulated in AEC and downregulated in VEC"], ["GABBR1", "γ-Aminobutyric acid (GABA) B receptor, 1", "Concordant in AEC and VECUpregulated in AEC and VEC"], ["LMF1", "Lipase maturation factor 1", "Concordant in VECUpregulated in AEC and VEC"], ["NCKAP5", "NCK-associated protein 5", "Concordant in AEC and VECUpregulated in AEC and VEC"], ["SKIL", "SKI-like oncogene", "Concordant in VECUpregulated in AEC and VEC"], ["SULF2", "Sulfatase 2", "Concordant in VECUpregulated in AEC and VEC"]], "row_count": 7, "column_count": 3, "numeric_cells": 4, "header_rows": 1, "locator": "section[17]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:30091044:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:35ff173e911d31282c2b71c0c4c3a79c3fb3e78458c184f0a02eca29d8b52957", "bytes": 1872, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[2]#Tab4", "version": null, "note": "Top five significantly enriched molecular functions in Ingenuity Pathway Analysis for genes whose expression is potentially regulated by DNA methylation by GDM in AEC and VEC", "structure": {"pmcid": "PMC6182654", "section_index": 17, "section_title": "Concordant DNA methylation and expression changes in fetoplacental AEC and VEC", "row_count": 23, "column_count": 4}, "table": {"label": "Table 4", "caption": "Top five significantly enriched molecular functions in Ingenuity Pathway Analysis for genes whose expression is potentially regulated by DNA methylation by GDM in AEC and VEC", "rows": [["Regulation", "Molecular function", "p value", "Scorea"], ["AEC"], ["Hypomethylated/upregulated", "Cell morphologyb", "5.79 × 10−7 to 1.63 × 10−2", "40"], ["Cellular movementb", "2.54 × 10−5 to 1.56 × 10−2", "35"], ["Cell-to-cell signalling and interaction", "5.75 × 10−5 to 1.63 × 10−2", "28"], ["Carbohydrate metabolism", "1.98 × 10−4 to 1.63 × 10−2", "14"], ["Cellular development", "1.98 × 10−4 to 1.63 × 10−2", "33"], ["Hypermethylated/downregulated", "Cell-to-cell signalling and interaction", "2.18 × 10−5 to 4.61 × 10−2", "11"], ["Cellular compromise", "2.18 × 10−5 to 1.82 × 10−2", "10"], ["Molecular transport", "5.86 × 10−4 to 4.74 × 10−2", "10"], ["Cell cycle", "7.69 × 10−4 to 4.86 × 10−2", "11"], ["Cellular assembly and organisationb", "7.69 × 10−4 to 4.61 × 10−2", "16"], ["VEC"], ["Hypomethylated/upregulated", "Carbohydrate metabolism", "4.55 × 10−5 to 1.17 × 10−2", "4"], ["Small molecule biochemistry", "4.55 × 10−5 to 2.72 × 10−2", "11"], ["Cell morphologyb", "1.51 × 10−4 to 2.72 × 10−2", "23"], ["Cellular function and maintenance", "1.51 × 10−4 to 2.62 × 10−2", "20"], ["Cell-to-cell signalling and interaction", "1.58 × 10−4 to 2.72 × 10−2", "11"], ["Hypermethylated/downregulated", "Cell cycle", "1.48 × 10−4 to 4.85 × 10−2", "4"], ["Protein synthesis", "4.12 × 10−4 to 1.42 × 10−2", "6"], ["Cellular movementb", "4.76 × 10−4 to 4.58 × 10−2", "3"], ["Cell death and survival", "1.17 × 10−3 to 4.98 × 10−2", "5"], ["Cell morphologyb", "1.42 × 10−3 to 4.71 × 10−2", "4"]], "row_count": 23, "column_count": 4, "numeric_cells": 40, "header_rows": 1, "locator": "section[17]/table-wrap[2]#Tab4"}}], "gaps": ["asset:data:geo:GSE103552 not downloaded", "asset:data:geo:GSE103552 licence not read", "asset:data:geo:GSE106099 not downloaded", "asset:data:geo:GSE106099 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "meta_analysis", "specific": 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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": ["random_effects_pool"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: random_effects."}, "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": ["GSE106099", "GSE103552"], "resolved_accessions": ["GSE106099", "GSE103552"], "statements": ["DNA methylation and gene expression datasets generated and analysed during the current study are available at the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo) under accession numbers GSE106099 and GSE103552, respectively."], "basis": "The paper names GSE106099, GSE103552 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": ["random_effects_pool"], "assets": ["source:pmid:30091044", "data:geo:GSE103552", "asset:table:pmid:30091044:1", "asset:table:pmid:30091044:2", "asset:table:pmid:30091044:3", "asset:table:pmid:30091044:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE103552"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": null, "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 0, "usage": {}}, "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:30091044", "type": "paper", "label": "pmid:30091044"}, {"id": "source:pmid:30091044", "type": "manuscript", "label": "PMID 30091044 full text"}, {"id": "data:geo:GSE103552", "type": "dataset", "label": "GEO GSE103552"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30091044", "type": "paper", "label": "pmid:30091044"}, {"id": "source:pmid:30091044", "type": "manuscript", "label": "PMID 30091044 full text"}, {"id": "data:geo:GSE103552", "type": "dataset", "label": "GEO GSE103552"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30091044", "type": "extraction", "used": ["source:pmid:30091044"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE103552", "type": "accession_resolution", "used": ["data:geo:GSE103552"], "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:30091044", "parent_hash": "sha256:0a14671ca7320b2ed8dba8b9ba33df13c442292be99d7b75a0fdd59cea9037a6", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE103552 licence not read", "asset:data:geo:GSE103552 not downloaded", "asset:data:geo:GSE106099 licence not read", "asset:data:geo:GSE106099 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "meta_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["random_effects_pool"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The limma package [21] was used to fit a linear model to compare dAEC and dVEC vs control samples, with patient as random effect and allowing for batch effects."], "order_basis": "analysis_only", "id": "assay:1"}]},"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":"2026-11-04T02:14:33+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}}}