{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31502424", "kind": "science-record", "revision": 9, "content_hash": "sha256:e0f642ccf7eb8183836b7f95b8ce4d0c7f7b46b7a1861467329820da56cc2d39", "created_at": "2026-11-01T15:40:49Z", "updated_at": "2026-11-01T22:44:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of miRNA-mRNA regulatory network revealed key genes induced by aflatoxin B1 exposure in primary human hepatocytes.", "doi": "10.1002/mgg3.971", "pmid": "31502424", "authors": ["Ziyang Zhang", "Dongyang Tang", "Bin Wang", "Zhiwei Wang", "Mingjiu Liu"], "journal": "Molecular genetics & genomic medicine", "year": 2019, "abstract": "BACKGROUND: Aflatoxin B1 (AFB1) exposure is a crucial factor to initiate hepatocellular carcinoma (HCC). However, comprehensive microRNA (miRNA)-message RNA (mRNA) regulatory network regarding AFB1-associated HCC is still lacking. This work was aimed to identify miRNA-mRNA network in primary human hepatocytes after AFB1 exposure.\nMETHODS: A miRNA expression dataset GSE71540 obtained from the gene expression omnibus (GEO) was used to identify differentially expressed miRNAs (DEMs) after AFB1 exposure using GEO2R. Target genes of these DEMs were identified using TargetScan V_7.2, miRDB, PITA, miRanda, and miRTarBase. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed at Database for Annotation, Visualization and Integrated Discovery (DAVID). miRNA-mRNA regulatory network was established by analyzing three enriched KEGG pathways significantly correlated with HCC onset and then visualized at CytoScape.\nRESULTS: In this work, nine upregulated and nine downregulated DEMs were identified. Functional enrichment analyses showed that these predicted target genes were significantly associated with cancer development. Analysis of three enriched pathways related to the onset of HCC identified 13 and nine target genes for upregulated DEMs and downregulated DEMs, respectively. Subsequently, the miRNA-mRNA regulatory networks were constructed.\nCONCLUSIONS: In conclusion, miRNA-mRNA regulatory network was established, which will help to understand the mechanism underlying the AFB1-induced onset of HCC.", "claims": [{"id": "claim-method", "statement": "GEO2R, an algorithm based on R language limma package, was employed to analyze differentially expressed miRNAs (DEMs) in this dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31502424", "locator": "sections[4] \"Identification of differentially expressed miRNAs\" paragraph 2", "quote": "GEO2R, an algorithm based on R language limma package, was employed to analyze differentially expressed miRNAs (DEMs) in this dataset."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE71540, obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71540), is a miRNA expression profile dataset submitted by Linda Rieswijk.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31502424", "locator": "sections[3] \"Microarray dataset\" paragraph 2", "quote": "GSE71540, obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71540), is a miRNA expression profile dataset submitted by Linda Rieswijk."}], "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:31502424"], "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:GSE71540"], "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:GSE71540"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31502424", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/mgg3.971", "sha256": 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"hsa‐miR‐513b, hsa‐miR‐4286, hsa‐miR‐505‐3p, hsa‐miR‐4257"]], "row_count": 10, "column_count": 2, "numeric_cells": 11, "header_rows": 1, "locator": "section[11]/table-wrap[2]#mgg3971-tbl-0002"}}, {"id": "asset:table:pmid:31502424:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:989b0188e9de2d841ebb2fd358a59e6aa02ec9d82f2b014cbfb7edfb8a5a97e9", "bytes": 1498, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#mgg3971-tbl-0003", "version": null, "note": "GO analysis of targets of the upregulated DEMs", "structure": {"pmcid": "PMC6825861", "section_index": 12, "section_title": "Functional analyses of the upregulated or downregulated DEMs", "row_count": 16, "column_count": 5}, "table": {"label": "Table 3", "caption": "GO analysis of targets of the upregulated DEMs", "rows": [["Category", "ID", "Description", "Count", "p value"], ["Biological process", "GO:0045944", "Positive regulation of transcription from RNA polymerase II promoter", "174", "5.08E‐22"], ["GO:0000122", "Negative regulation of transcription from RNA polymerase II promoter", "121", "1.66E‐13"], ["GO:0045893", "Positive regulation of transcription, DNA‐templated", "94", "1.00E‐12"], ["GO:0006366", "Transcription from RNA polymerase II promoter", "91", "1.22E‐11"], ["GO:0045892", "Negative regulation of transcription, DNA‐templated", "80", "2.79E‐08"], ["Molecular function", "GO:0005515", "Protein binding", "934", "3.94E‐29"], ["GO:0003700", "Transcription factor activity, sequence‐specific DNA binding", "142", "1.69E‐11"], ["GO:0001077", "Transcriptional activator activity, RNA polymerase II core promoter proximal region sequence‐specific binding", "49", "6.02E‐09"], ["GO:0000978", "RNA polymerase II core promoter proximal region sequence‐specific DNA binding", "64", "8.19E‐09"], ["GO:0043565", "Sequence‐specific DNA binding", "81", "5.53E‐08"], ["Cellular component", "GO:0005654", "Nucleoplasm", "351", "1.12E‐19"], ["GO:0005737", "Cytoplasm", "563", "1.53E‐16"], ["GO:0005634", "Nucleus", "579", "1.72E‐16"], ["GO:0005829", "Cytosol", "372", "1.52E‐12"], ["GO:0016020", "Membrane", "266", "2.97E‐12"]], "row_count": 16, "column_count": 5, "numeric_cells": 45, "header_rows": 1, "locator": "section[12]/table-wrap[1]#mgg3971-tbl-0003"}}, {"id": "asset:table:pmid:31502424:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:64c18d1e77f5564fffd65ce9743e574332670b6c06de6f6fd580854b275c500f", "bytes": 1185, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#mgg3971-tbl-0004", "version": null, "note": "GO analysis of targets of the downregulated DEMs", "structure": {"pmcid": "PMC6825861", "section_index": 12, "section_title": "Functional analyses of the upregulated or downregulated DEMs", "row_count": 16, "column_count": 5}, "table": {"label": "Table 4", "caption": "GO analysis of targets of the downregulated DEMs", "rows": [["Category", "ID", "Description", "Count", "p value"], ["Biological process", "GO:0050789", "Regulation of biological process", "1751", "3.20E‐14"], ["GO:0032502", "Developmental process", "971", "2.54E‐12"], ["GO:0065007", "Biological regulation", "1823", "4.59E‐12"], ["GO:0008152", "Metabolic process", "1739", "1.54E‐09"], ["GO:0009987", "Cellular process", "2,326", "2.36E‐08"], ["Molecular function", "GO:0003700", "Transcription factor activity, sequence‐specific DNA binding", "211", "2.91E‐10"], ["GO:0005515", "Protein binding", "1,418", "1.46E‐09"], ["GO:0003677", "DNA binding", "329", "2.10E‐09"], ["GO:0046872", "Metal ion binding", "371", "5.25E‐06"], ["GO:0,004,674", "Protein serine/threonine kinase activity", "87", "9.51E‐06"], ["Cellular component", "GO:0005654", "Nucleoplasm", "513", "2.50E‐10"], ["GO:0005634", "Nucleus", "912", 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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":"2026-11-04T01:50:30+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}}}