{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37086280", "kind": "science-record", "revision": 7, "content_hash": "sha256:893745a7921b6836b805380af9dd82cf2699c291315d29c7dffc9a49bc2414d8", "created_at": "2026-11-01T19:01:45Z", "updated_at": "2026-11-01T23:50:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of differential gene immune infiltration and clinical characteristics of skin cutaneous melanoma based on systems biology and drug repositioning methods to identify drug candidates for skin cutaneous melanoma.", "doi": "10.1007/s00210-023-02461-1", "pmid": "37086280", "authors": ["Shengyong Long", "Jing Xu", "Hai Huang"], "journal": "Naunyn-Schmiedeberg's archives of pharmacology", "year": 2023, "abstract": "Skin cutaneous melanoma (SKCM) has a low early detection rate and a high mortality rate. There are many problems such as side effects and drug resistance in existing therapeutic drugs. Current studies have confirmed that SKCM pathogenesis-related genes promote the invasion and metastasis of cutaneous melanoma, but their roles in the tumor microenvironment (TME) remain unclear. Network pharmacology provides new opportunities for drug repurposing and repositioning, and is a fast, safe, and inexpensive drug discovery method to find new drugs for the treatment of SKCM. In this study, based on 3 databases (KEGG, OMIM, and Genotype) to obtain SKCM-related genes, and TCGA SKCM dataset, SKCM differential genes in GSE3189 and GSE46517 were intersected to identify SKCM pathogenesis-related differential genes, and the differential genes were immune infiltration and analysis, For survival analysis, a prognostic nomogram risk model was constructed based on the results of multivariate Cox regression analysis for risk stratification and prognosis prediction, then focused on the differential expression of ZC3H12A and its effect on TME. Finally, the protein interaction network method was used to quantify the similarity between 684 drug targets and skin melanoma, and to screen out drugs similar to skin melanoma. Based on 3 databases of KEGG, OMIM, and Genotype, 294 SKCM-related genes and 18 SKCM pathogenesis-related differential genes were obtained, and 18 SKCM pathogenesis-related differential genes were significantly correlated with TME. The constructed prognostic nomogram risk model predicted performance better and provided valuable information for immunotherapy. Multivariate Cox regression analysis and K-M analysis showed that ZC3H12A was a differentially expressed gene affecting the prognosis of SKCM and promoted the infiltration of anti-tumor immune cells CD8 + T cells, B cells, and DC cells. Based on the analysis of the protein interaction network method, 43 drugs were found to have high potential in the treatment of SKCM, and the literature search of these 43 drugs was carried out, and 21 drugs were found to have experimental verification for the treatment of SKCM. Taken together, the differential genes associated with the pathogenesis of SKCM have important roles in the tumor immune microenvironment, clinicopathological features, and prognosis, especially ZC3H12A has a potential role in identifying early SKCM patients. At the same time, it provides a new strategy for the drug development of SKCM and provides a basis for the reuse of SKCM drugs.", "claims": [{"id": "claim-method", "statement": "The K-M survival curve was used to determine the difference in survival rate, and the log-rank test was used to evaluate the significant difference in survival time between the two groups, determining independence using univariate and multivariate Cox analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37086280", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "The K-M survival curve was used to determine the difference in survival rate, and the log-rank test was used to evaluate the significant difference in survival time between the two groups, determining independence using univariate and multivariate Cox analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original datasets analyzed in this study are available in the GEO database and the TCGA database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37086280", "locator": "sections[23] \"notes\" paragraph 1", "quote": "The original datasets analyzed in this study are available in the GEO database and the TCGA database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study constructed a prognostic nomogram based on three independent prognostic genes and stage variables that had a C-index of 0.732 and AUC values of 0.823, 0.795, and 0.792 for 2-, 4-, and 6-year outcomes, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37086280", "locator": "sections[13] \"Construction of prognostic model and correlational analysis\" paragraph 2", "quote": "The C-index was 0.732, and the ROC analysis showed that the AUC values for 2, 4, and 6 years were 0.823, 0.795, and 0.792, respectively (Fig. 3C)."}, {"asset": "source:pmid:37086280", "locator": "sections[13] \"Construction of prognostic model and correlational analysis\" paragraph 2", "quote": "A prognostic nomogram-based model was developed based on 3 independent prognostic genes (EGFR, TNFRSF21, ZC3H12A), independent prognostic indicators for T, M, and N stages (Fig. 3A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study constructed a prognostic nomogram based on three independent prognostic genes and stage variables that had a C-index of 0.732 and AUC values of 0.823, 0.795, and 0.792 for 2-, 4-, and 6-year outcomes, respectively.", "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:37086280"], "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. 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"band": "verbatim", "quote": "The K-M survival curve was used to determine the difference in survival rate, and the log-rank test was used to evaluate the significant difference in survival time between the two groups, determining independence using univariate and multivariate Cox analysis."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "KM"}}, {"id": "method-4", "family": "survival_analysis", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE100797", "GSE78220", "GSE133713", "GSE98394", "GSE190113", "GSE22153", "GSE54467", "GSE53118", "GSE22154", "GSE19234", "GSE59455", "GSE46517", "GSE99898", "GSE15605", "GSE6590293", "GSE3189", "GSE98314"], "resolved_accessions": ["GSE100797", "GSE78220", "GSE133713", "GSE98394", "GSE190113", "GSE22153", "GSE54467", "GSE53118", "GSE22154", "GSE19234", "GSE59455", "GSE46517", "GSE99898", "GSE15605", "GSE3189", "GSE98314"], "statements": ["The original datasets analyzed in this study are available in the GEO database and the TCGA database."], "basis": "The paper names GSE100797, GSE78220, GSE133713, GSE98394, GSE190113, GSE22153, GSE54467, GSE53118, GSE22154, GSE19234, GSE59455, GSE46517, GSE99898, GSE15605, GSE3189, GSE98314 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:37086280", "data:geo:GSE100797"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE100797"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:37:20Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15491, "completion_tokens": 2423, "cached_tokens": 256}}, "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:37086280", "type": "paper", "label": "pmid:37086280"}, {"id": "source:pmid:37086280", "type": "manuscript", "label": "PMID 37086280 full text"}, {"id": "data:geo:GSE100797", "type": "dataset", "label": "GEO GSE100797"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37086280", "type": "paper", "label": "pmid:37086280"}, {"id": "source:pmid:37086280", "type": "manuscript", "label": "PMID 37086280 full text"}, {"id": "data:geo:GSE100797", "type": "dataset", "label": "GEO GSE100797"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37086280", "type": "extraction", "used": ["source:pmid:37086280"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE100797", "type": "accession_resolution", "used": ["data:geo:GSE100797"], "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:37086280", "parent_hash": "sha256:421d5f281f9504a729fda2fc579a210aee90e1c3ed592140c4de23ee32371e12", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE100797 licence not read", "asset:data:geo:GSE100797 not downloaded", "asset:data:geo:GSE133713 licence not read", "asset:data:geo:GSE133713 not downloaded", "asset:data:geo:GSE15605 licence not read", "asset:data:geo:GSE15605 not downloaded", "asset:data:geo:GSE190113 licence not read", "asset:data:geo:GSE190113 not downloaded", "asset:data:geo:GSE19234 licence not read", "asset:data:geo:GSE19234 not downloaded", "asset:data:geo:GSE22153 licence not read", "asset:data:geo:GSE22153 not downloaded", "asset:data:geo:GSE22154 licence not read", "asset:data:geo:GSE22154 not downloaded", "asset:data:geo:GSE3189 licence not read", "asset:data:geo:GSE3189 not downloaded", "asset:data:geo:GSE46517 licence not read", "asset:data:geo:GSE46517 not downloaded", "asset:data:geo:GSE53118 licence not read", "asset:data:geo:GSE53118 not downloaded", "asset:data:geo:GSE54467 licence not read", "asset:data:geo:GSE54467 not downloaded", "asset:data:geo:GSE59455 licence not read", "asset:data:geo:GSE59455 not downloaded", "asset:data:geo:GSE6590293 licence not read", "asset:data:geo:GSE6590293 not downloaded", "asset:data:geo:GSE78220 licence not read", "asset:data:geo:GSE78220 not downloaded", "asset:data:geo:GSE98314 licence not read", "asset:data:geo:GSE98314 not downloaded", "asset:data:geo:GSE98394 licence not read", "asset:data:geo:GSE98394 not downloaded", "asset:data:geo:GSE99898 licence not read", "asset:data:geo:GSE99898 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The K-M survival curve was used to determine the difference in survival rate, and the log-rank test was used to evaluate the significant difference in survival time between the two groups, determining independence using univariate and multivariate Cox analysis."], "order_basis": "analysis_only", "id": "assay:1"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T01:20:22+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}}}