{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33329727", "kind": "science-record", "revision": 7, "content_hash": "sha256:cf281acc192e7dfcfc23dca25a1029189f4a7894e3de3c2d89902c1dd84de8bc", "created_at": "2026-11-01T15:41:19Z", "updated_at": "2026-11-01T22:02:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Differential Expression and Bioinformatics Analysis of circRNA in Non-small Cell Lung Cancer.", "doi": "10.3389/fgene.2020.586814", "pmid": "33329727", "authors": ["Qiuwen Sun", "Xia Li", "Muchen Xu", "Li Zhang", "Haiwei Zuo", "Yong Xin", "Longzhen Zhang", "Ping Gong"], "journal": "Frontiers in genetics", "year": 2020, "abstract": "Circular RNA (CircRNA) plays an important role in tumorigenesis and progression of non-small cell lung cancer (NSCLC), but the pathogenesis of NSCLC caused by circRNA has not been fully elucidated. This study aimed to investigate differentially expressed circRNAs and identify the underlying pathogenesis hub genes of NSCLC by comprehensive bioinformatics analysis. Data of gene expression microarrays (GSE101586, GSE101684, and GSE112214) were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed circRNAs (DECs) were obtained by the \"limma\" package of R programs and the overlapping operation was implemented of DECs. CircBase database and Cancer-Specific CircRNA database (CSCD) were used to find miRNAs binding to DECs. Target genes of the found miRNAs were identified utilizing Perl programs based on miRDB, miRTarBase, and TargetScan databases. Functional and enrichment analyses of selected target genes were performing using the \"cluster profiler\" package. Protein-protein interaction (PPI) network was constructed by the Search Tool for the STRING database and module analysis of selected hub genes was performed by Cytoscape 3.7.1. Survival analysis of hub genes were performed by Gene Expression Profiling Interactive Analysis (GEPIA). Respectively, 1 DEC, 249 DECs, and 101 DECs were identified in GSE101586, GSE101684, and GSE112214. A total of eight overlapped circRNAs, 43 miRNAs and 427 target genes were identified. Gene Ontology (GO) enrichment analysis showed these target genes were enriched in biological processes of regulation of histone methylation, Ras protein signal transduction and covalent chromatin modification etc. Pathway enrichment analysis showed these target genes are mainly involved in AMPK signaling pathway, signaling pathways regulating pluripotency of stem cells and insulin signaling pathway etc. A PPI network was constructed based on 427 target genes of the 43 miRNAs. Ten hub genes were found, of which the expression of MYLIP, GAN, and CDC27 were significantly related to NSCLC patient prognosis. Our study provide a deeper understanding the circRNAs-miRNAs-target genes by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of NSCLC. MYLIP, GAN, and CDC27 genes might serve as novel biomarker for precise treatment and prognosis of NSCLC in the future.", "claims": [{"id": "claim-method", "statement": "Subsequently, the fold-change and Student's t testing were used for screening for DECs in the three sets, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33329727", "locator": "sections[5] \"2.3. Identification of Differentially Expressed circRNAs\" paragraph 2", "quote": "Subsequently, the fold-change and Student's t testing were used for screening for DECs in the three sets, respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/gds/?term=GSE101684; https://www.ncbi.nlm.nih.gov/gds/?term=GSE112214; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101586.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33329727", "locator": "sections[18] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/gds/?term=GSE101684; https://www.ncbi.nlm.nih.gov/gds/?term=GSE112214; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101586."}], "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:33329727"], "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:GSE101586"], "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:GSE101586"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33329727", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2020.586814", "sha256": "sha256:5b6a1fedb7bb3b41c1e713aa8255db757cf0350e7a6f33b8ebe46693ace0d471", "bytes": 27707, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2020.586814", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7732606", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE101586", "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=GSE101586", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE101586", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/gds/?term=GSE101684; https://www.ncbi.nlm.nih.gov/gds/?term=GSE112214; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101586.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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Interaction of circRNA-miRNA-Target Genes", "row_count": 11, "column_count": 2}, "table": {"label": "Table 2", "caption": "Target genes of the first 10 miRNAs in hsa_circ_0008234.", "rows": [["miRNA", "Target-Genes"], ["hsa-miR-1272", "RTN4,PHKA1,BCAS2,COIL,G2E3,FAM83C,TMEM167A,SMNDC1,SAR1B"], ["hsa-miR-1322", "IRF2BPL,C11orf58,CTCF,UCHL5"], ["hsa-miR-150-5p", "PDCD4,MTMR9,PDIA6,HILPDA,GK5,ELK1,XPNPEP3,AHI1,EREG,ZEB1,AIFM2"], ["hsa-miR-1910-5p", "CLIC4,GSK3B,MTHFD2"], ["hsa-miR-2116-3p", "MBD6,EREG,ZBTB18,AP4S1,SRRM4,TXNIP,KRBOX4"], ["hsa-miR-296-3p", "TCERG1,HILPDA,ZNF138,ZNF117,GRINA,ZNF99"], ["hsa-miR-31-3p", "EPB41L4B,SLC30A5,FRS2,PLEKHB2,CRK,CHMP4B,BACH1"], ["hsa-miR-3677-5p", "TBC1D12,SLC7A1,NCMAP,HMGXB3"], ["hsa-miR-4264", "ESR1,KLHL15,PALM2,TM4SF1,ADIPOR2,SLCO3A1,SENP1,THRB,FOXK2,PODXL"], ["hsa-miR-4520-3p", "PRKX,RAB25,H2AFZ,RAB10,MYOCD,ABAT,NUFIP2"]], "row_count": 11, "column_count": 2, "numeric_cells": 18, "header_rows": 1, "locator": "section[12]/table-wrap[2]#T2"}}], "gaps": ["asset:data:geo:GSE101586 not downloaded", "asset:data:geo:GSE101586 licence not read", "asset:data:geo:GSE101684 not downloaded", "asset:data:geo:GSE101684 licence not read", "asset:data:geo:GSE112214 not downloaded", "asset:data:geo:GSE112214 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "limma"}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Protein-protein interaction"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pathway enrichment"}}, {"id": "method-4", "family": null, "specific": null, "label": "Student's t testing", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Subsequently, the fold-change and Student's t testing were used for screening for DECs in the three sets, respectively."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE101586", "GSE101684", "GSE112214"], "resolved_accessions": ["GSE101586", "GSE101684", "GSE112214"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/gds/?term=GSE101684; https://www.ncbi.nlm.nih.gov/gds/?term=GSE112214; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101586."], "basis": "The paper names GSE101586, GSE101684, GSE112214 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:33329727", "data:geo:GSE101586", "asset:table:pmid:33329727:1", "asset:table:pmid:33329727:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE101586"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:25:14Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 21199, "completion_tokens": 1565, "cached_tokens": 520}}, "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:33329727", "type": "paper", "label": "pmid:33329727"}, {"id": "source:pmid:33329727", "type": "manuscript", "label": "PMID 33329727 full text"}, {"id": "data:geo:GSE101586", "type": "dataset", "label": "GEO GSE101586"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33329727", "type": "paper", "label": "pmid:33329727"}, {"id": "source:pmid:33329727", "type": "manuscript", "label": "PMID 33329727 full text"}, {"id": "data:geo:GSE101586", "type": "dataset", "label": "GEO GSE101586"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33329727", "type": "extraction", "used": ["source:pmid:33329727"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE101586", "type": "accession_resolution", "used": ["data:geo:GSE101586"], "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:33329727", "parent_hash": "sha256:c4cb31a96c6f8c6603a70719accdd67478bd27d913b5c276b077c706c85878ff", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE101586 licence not read", "asset:data:geo:GSE101586 not downloaded", "asset:data:geo:GSE101684 licence not read", "asset:data:geo:GSE101684 not downloaded", "asset:data:geo:GSE112214 licence not read", "asset:data:geo:GSE112214 not downloaded", "execution.not_run", "method.reader_named_unmapped", "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": ["als and Methods 2.2. 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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. 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}}}