{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33479394", "kind": "science-record", "revision": 9, "content_hash": "sha256:37d5e9225774dd46860a6f417ab1ea722564bf6b4bfc334cf40c35dfff56858c", "created_at": "2026-11-01T15:41:23Z", "updated_at": "2026-11-01T22:46:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms.", "doi": "10.1038/s41598-021-81667-w", "pmid": "33479394", "authors": ["Hiroshi Nakano", "Motonobu Saito", "Shotaro Nakajima", "Katsuharu Saito", "Yuko Nakayama", "Koji Kase", "Leo Yamada", "Yasuyuki Kanke", "Hiroyuki Hanayama", "Hisashi Onozawa", "Hirokazu Okayama", "Shotaro Fujita", "Wataru Sakamoto", "Zenichiro Saze", "Tomoyuki Momma", "Kosaku Mimura", "Shinji Ohki", "Akiteru Goto", "Koji Kono"], "journal": "Scientific reports", "year": 2021, "abstract": "Epstein-Barr virus-positive gastric cancer [EBV (+) GC] is a distinct GC subtype with unique genetic and epigenetic aberrations. Here, we examined resected GC samples and publicly available microarray data and The Cancer Genome Atlas (TCGA) database to identify the mechanism underlying overexpression of PD-L1 in EBV (+) GC. We found that high levels of PD-L1 overexpression in EBV (+) GC were caused by focal amplification of CD274. By contrast, relatively high expression of PD-L1 in tumor tissue and infiltrating immune cells correlated with CD8 lymphocyte infiltration and IFN-γ expression via IRF3 activation. Since we reported previously that PD-L1 expression is associated both with the presence of CD8 T cells in the tumor microenvironment and with IFN-γ expression in GC, we examined a database to see whether IFN-γ-associated overexpression of PD-L1 plays a significant role in EBV (+) GC. Immunohistochemical staining showed that expression of the IRF3 signature in clinical GC samples was higher in EBV (+) than in EBV (-) cases. The data presented herein reveal a unique dual mechanism underlying PD-L1 overexpression in EBV (+) GC: high focal amplification of CD274 or IFN-γ-mediated signaling via activation of IRF3.", "claims": [{"id": "claim-method", "statement": "Mann–Whitney U test were used to determine differences between two variables. Spearman’s correlation was used to evaluate the correlations between levels of expression. Pearson correlation analysis was used to examine the relationships between two parameters. ANOVA test was used for multiple comparisons.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33479394", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "Mann–Whitney U test were used to determine differences between two variables. Spearman’s correlation was used to evaluate the correlations between levels of expression. Pearson correlation analysis was used to examine the relationships between two parameters. ANOVA test was used for multiple comparisons."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We utilized microarray gene methylation profiles from 54 patients with GC and EBV-infected GC cells, using Akata system of recombinant EBV, deposited as GSE31789 on the basis of Illumina Infinium HumanMethylation27 BeadChip5 and analyzed according to our previous study31.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33479394", "locator": "sections[10] \"Microarray data analysis\" paragraph 2", "quote": "We utilized microarray gene methylation profiles from 54 patients with GC and EBV-infected GC cells, using Akata system of recombinant EBV, deposited as GSE31789 on the basis of Illumina Infinium HumanMethylation27 BeadChip5 and analyzed according to our previous study31."}], "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:33479394"], "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:GSE31787"], "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:GSE31787"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33479394", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-021-81667-w", "sha256": 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system of recombinant EBV, deposited as GSE31789 on the basis of Illumina Infinium HumanMethylation27 BeadChip5 and analyzed according to our previous study31.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We utilized microarray gene methylation profiles from 54 patients with GC and EBV-infected GC cells, using Akata system of recombinant EBV, deposited as GSE31789 on the basis of Illumina Infinium HumanMethylation27 BeadChip5 and analyzed according to our previous study31.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM788498", "GSM788499", "GSM788500", "GSM788501"], "sample_count": 4, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Aberrant DNA methylation epigenotype expanding to non-polycomb target genes, induced by Epstein-Barr virus infection in human gastric cancer [Affymetrix Expression]", "resolution_checked_at": 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"30–92", "48–81", "59–92", "30–91"], ["Gender-no. (%)"], ["Male", "283 (71)", "20 (74)", "21 (64)", "242 (71)"], ["Female", "118 (29)", "7 (26)", "12 (36)", "99 (29)"], ["Tumor location"], ["Upper", "128 (32)", "17 (63)", "3 (9)", "108 (32)"], ["Middle", "136 (34)", "7 (26)", "8 (24)", "121 (35)"], ["Lower", "124 (31)", "1 (4)", "21 (64)", "102 (30)"], ["Whole", "6 (1)", "1 (4)", "0", "5 (1)"], ["N/A", "7 (2)", "1 (4)", "1 83)", "5 (1)"], ["Histological type-no. (%)"], ["Differentiated", "203 (51)", "11 (41)", "21 (64)", "176 (52)"], ["Undifferentiated", "191 (49)", "16 (59)", "12 (36)", "165 (48)"], ["Histological type-no. (%)"], ["Conventional-type adenocarcinoma", "–", "13 (48)", "–", "–"], ["Crohn's disease-like lymphoid reaction", "–", "2 (7)", "–", "–"], ["Lymphoepithelioma-like carcinoma", "–", "12 (44)", "–", "–"], ["TNM stage-no. (%)"], ["I", "219 (55)", "11 (41)", "16 (48)", "192 (56)"], ["II", "79 (20)", "6 (22)", "8 (24)", "65 (19)"], ["III", "70 (17)", "6 (22)", "6 (18)", "58 (17)"], ["IV", "33 (8)", "4 (15)", "4 (12)", "26 (8)"], ["LN metastasis-no. (%)"], ["Positive", "247 (62)", "11 (41)", "12 (36)", "132 (39)"], ["Negative", "154 (38)", "16 (59)", "21 (64)", "209 (61)"], ["Lymphatic invasion-no. (%)"], ["Present", "218 (54)", "14 (52)", "20 (60)", "184 (54)"], ["Absent", "182 (45)", "13 (48)", "12 (36)", "157 (46)"], ["N/A", "1", "0", "1 (3)", "0"], ["Venous invasion-no. (%)"], ["Present", "228 (57)", "21 (78)", "20 (60)", "187 (55)"], ["Absent", "172 (42)", "6 (22)", "12 (36)", "154 (45)"], ["N/A", "1 (1)", "0", "1 (3)", "0"], ["Mismatch repair (MMR)-no. (%)"], ["Deficient MMR", "33 (8.2)", "0", "33 (100)", "0"], ["Proficient MMR", "368 (92)", "27 (100)", "0", "341 (100)"], ["Epstein-Barr virus (EBV)-no. (%)"], ["Positive", "27 (6.7)", "27 (100)", "0", "0"], ["Negative", "374 (93.3)", "0", "33 (100)", "341 (100)"]], "row_count": 42, "column_count": 5, "numeric_cells": 115, "header_rows": 1, "locator": "section[3]/table-wrap[1]#Tab1"}}], "gaps": ["asset:data:geo:GSE31787 not downloaded", "asset:data:geo:GSE31787 licence not read", "asset:data:geo:GSE31789 not downloaded", "asset:data:geo:GSE31789 licence not read", "asset:data:geo:GSE51575 not downloaded", "asset:data:geo:GSE51575 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Mann–Whitney U test were used to determine differences between two variables. Spearman’s correlation was used to evaluate the correlations between levels of expression. Pearson correlation analysis was used to examine the relationships between two parameters. ANOVA test was used for multiple comparisons."}}, {"id": "method-2", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}], "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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "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": ["GSE31789", "GSE31787", "GSE51575"], "resolved_accessions": ["GSE31789", "GSE31787", "GSE51575"], "statements": ["We utilized microarray gene methylation profiles from 54 patients with GC and EBV-infected GC cells, using Akata system of recombinant EBV, deposited as GSE31789 on the basis of Illumina Infinium HumanMethylation27 BeadChip5 and analyzed according to our previous study31."], "basis": "The paper names GSE31789, GSE31787, GSE51575 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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:33479394", "data:geo:GSE31787", "asset:table:pmid:33479394:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE31787"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:26:34Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 28355, "completion_tokens": 2241, "cached_tokens": 784}}, "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:33479394", "type": "paper", "label": "pmid:33479394"}, {"id": "source:pmid:33479394", "type": "manuscript", "label": "PMID 33479394 full text"}, {"id": "data:geo:GSE31787", "type": "dataset", "label": "GEO GSE31787"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33479394", "type": "paper", "label": "pmid:33479394"}, {"id": "source:pmid:33479394", "type": "manuscript", "label": "PMID 33479394 full text"}, {"id": "data:geo:GSE31787", "type": "dataset", "label": "GEO GSE31787"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33479394", "type": "extraction", "used": ["source:pmid:33479394"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE31787", "type": "accession_resolution", "used": ["data:geo:GSE31787"], "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:33479394", "parent_hash": "sha256:2b197b744575d48a0b6b738d06bca6e60642d023e746e22453a701df091f7ae1", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE31787 licence not read", "asset:data:geo:GSE31787 not downloaded", "asset:data:geo:GSE31789 licence not read", "asset:data:geo:GSE31789 not downloaded", "asset:data:geo:GSE51575 licence not read", "asset:data:geo:GSE51575 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["D-L1 plays a significant role in EBV (+) GC. 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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":"2026-11-04T01:34:44+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}}}