{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29340037", "kind": "science-record", "revision": 9, "content_hash": "sha256:4751d0203a37600ee4ec1418823ab6594e050ff2f7429a39674c5568dea2b393", "created_at": "2026-11-01T15:40:31Z", "updated_at": "2026-11-01T22:43:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Systemic bioinformatics analysis of recurrent aphthous stomatitis gene expression profiles.", "doi": "10.18632/oncotarget.22347", "pmid": "29340037", "authors": ["Jian Wu", "Zheng-Ping Chen", "An-Quan Shang", "Wei-Wei Wang", "Zong-Ning Chen", "Yun-Juan Tao", "Yue Zhou", "Wan-Xiang Wang"], "journal": "Oncotarget", "year": 2017, "abstract": "Recurrent aphthous stomatitis (RAS) represents the most common chronic oral diseases with the prevalence ranges from 5% to 25% for different populations. Its pathogenesis remains poorly understood, which limits the development of effective drugs and treatment methods. In this study, we conducted systemic bioinformatics analysis of gene expression profiles from the Gene Expression Omnibus (GEO) to identify potential drug targets for RAS. We firstly downloaded the gene microarray datasets with the accession number of GSE37265 from GEO and performed robust multi-array (RMA) normalization with affy R programming package. Secondly, differential expression genes (DEGs) in RAS samples compared with control samples were identified based on limma package. Enriched gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs were obtained through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, protein-protein interaction (PPI) network was constructed based on the combination of HPRD and BioGrid databases. What's more, we identified modules of PPI network through MCODE plugin of Cytoscape for the purpose of screening of valuable targets. As a result, 915 genes were found to be significantly differential expression in RAS samples and biological processes related to immune and inflammatory response were significantly enriched in those genes. Network and module analysis identified FBXO6, ITGA4, VCAM1 and etc as valuable therapeutic targets for RAS. Finally, FBXO6, ITGA4, and VCAM1 were further confirmed by real time RT-PCR and western blot. This study should be helpful for the research and treatment of RAS.", "claims": [{"id": "claim-method", "statement": "the normalized expression profiles were then used for the identification of differential expression genes (DEGs) in RAS samples compared with adjacent non-ulcer tissues through linear models for microarray data (limma) version3.32.2", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29340037", "locator": "sections[10] \"Differential expression analysis\" paragraph 2", "quote": "the normalized expression profiles were then used for the identification of differential expression genes (DEGs) in RAS samples compared with adjacent non-ulcer tissues through linear models for microarray data (limma) version3.32.2"}], "state": "complete"}, {"id": "claim-data-access", "statement": "The RAS gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) with deposited by Baccaglini et al with the accession number of GSE37265 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37265). A total of 33 samples, i.e. 19 adjacent non-ulcer tissue and 14 RAS samples were included in the dataset. The commercial Affymetrix Human Genome U133 Plus 2.0 Array (GEO accession no.: GPL570) was used for the quantification of genome-wide gene expression values.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29340037", "locator": "sections[9] \"Gene expression profiles\" paragraph 2", "quote": "The RAS gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) with deposited by Baccaglini et al with the accession number of GSE37265 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37265). A total of 33 samples, i.e. 19 adjacent non-ulcer tissue and 14 RAS samples were included in the dataset. The commercial Affymetrix Human Genome U133 Plus 2.0 Array (GEO accession no.: GPL570) was used for the quantification of genome-wide gene expression values."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using limma analysis of the GSE37265 microarray dataset, the study identified 915 differentially expressed genes in RAS samples, with immune- and inflammation-related biological processes enriched, and nominated FBXO6, ITGA4, and VCAM1 as potential therapeutic targets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29340037", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We firstly downloaded the gene microarray datasets with the accession number of GSE37265 from GEO and performed robust multi-array (RMA) normalization with affy R programming package. Secondly, differential expression genes (DEGs) in RAS samples compared with control samples were identified based on limma package."}, {"asset": "source:pmid:29340037", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "As a result, 915 genes were found to be significantly differential expression in RAS samples and biological processes related to immune and inflammatory response were significantly enriched in those genes."}, {"asset": "source:pmid:29340037", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Network and module analysis identified FBXO6, ITGA4, VCAM1 and etc as valuable therapeutic targets for RAS."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using limma analysis of the GSE37265 microarray dataset, the study identified 915 differentially expressed genes in RAS samples, with immune- and inflammation-related biological processes enriched, and nominated FBXO6, ITGA4, and VCAM1 as potential therapeutic targets.", "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:29340037"], "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:GSE37265"], "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:GSE37265"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29340037", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/oncotarget.22347", "sha256": "sha256:b46a988c1a6a321421a71b9745720c891e6ff1c96c4bc1f6e35ae0edad689496", "bytes": 21079, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.18632/oncotarget.22347", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5762305", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE37265", "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=GSE37265", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE37265", "version": null, "note": "The RAS gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) with deposited by Baccaglini et al with the accession number of GSE37265 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37265). 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"band": "verbatim", "quote": "the normalized expression profiles were then used for the identification of differential expression genes (DEGs) in RAS samples compared with adjacent non-ulcer tissues through linear models for microarray data (limma) version3.32.2"}}, {"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"}}], "targets": [], "gaps": []}, "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": ["GSE37265"], "resolved_accessions": ["GSE37265"], "statements": ["The RAS gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) with deposited by Baccaglini et al with the accession number of GSE37265 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37265). A total of 33 samples, i.e. 19 adjacent non-ulcer tissue and 14 RAS samples were included in the dataset. The commercial Affymetrix Human Genome U133 Plus 2.0 Array (GEO accession no.: GPL570) was used for the quantification of genome-wide gene expression values."], "basis": "The paper names GSE37265 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:29340037", "data:geo:GSE37265", "asset:table:pmid:29340037:1", "asset:table:pmid:29340037:2", "asset:table:pmid:29340037:3", "asset:table:pmid:29340037:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE37265"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:33:24Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 49872, "completion_tokens": 2862, "cached_tokens": 18560}}, "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:29340037", "type": "paper", "label": "pmid:29340037"}, {"id": "source:pmid:29340037", "type": "manuscript", "label": "PMID 29340037 full text"}, {"id": "data:geo:GSE37265", "type": "dataset", "label": "GEO GSE37265"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29340037", "type": "paper", "label": "pmid:29340037"}, {"id": "source:pmid:29340037", "type": "manuscript", "label": "PMID 29340037 full text"}, {"id": "data:geo:GSE37265", "type": "dataset", "label": "GEO GSE37265"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29340037", "type": "extraction", "used": ["source:pmid:29340037"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE37265", "type": "accession_resolution", "used": ["data:geo:GSE37265"], "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:29340037", "parent_hash": "sha256:02294097224fbe502d1fb88c6b92bf445d5cbc52ce97fbdbaa6a580091bee3e6", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE37265 licence not read", "asset:data:geo:GSE37265 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["re further confirmed by real time RT-PCR and western blot. This study should be helpful for the resear"], "order_basis": "paper_text_order:1656", "id": "assay:1"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["the normalized expression profiles were then used for the identification of differential expression genes (DEGs) in RAS samples compared with adjacent non-ulcer tissues through linear models for microarray data (limma) version3.32.2"], "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":"2026-11-04T02:38:44+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}}}