{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:26413216", "kind": "science-record", "revision": 8, "content_hash": "sha256:f10a7465715749daf1ea1fbf9ab226091e3d4281a6fb40fea58f1992572e6a1c", "created_at": "2026-11-01T15:40:11Z", "updated_at": "2026-11-01T22:42:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx.", "doi": "10.18632/genesandcancer.69", "pmid": "26413216", "authors": ["Jayalakshmi Nair", "Prachi Jain", "Udita Chandola", "Vinayak Palve", "N R Harsha Vardhan", "Ram Bhupal Reddy", "Vikram D Kekatpure", "Amritha Suresh", "Moni Abraham Kuriakose", "Binay Panda"], "journal": "Genes & cancer", "year": 2015, "abstract": "Laryngo-pharyngeal squamous cell carcinomas are one of the most common head and neck cancers. Despite the presence of a large body of information, molecular biomarkers are not currently used in the diagnosis, treatment and management of patients for this group of cancer. Here, we have profiled expression of genes and microRNAs of larynx and hypopharynx tumors using high-throughput sequencing experiments. We found that matrix metalloproteinases along with SCEL, CRNN, KRT4, SPINK5, and TGM3 among others have significantly altered expression in these tumors. Alongside gene expression, the microRNAs hsa-miR-139, hsa-miR-203 and the hsa-miR-424/503 cluster have aberrant expression in these cancers. Using target genes for these microRNAs, we found the involvement of pathways linked to cell cycle, p53 signaling, and viral carcinogenesis significant (P-values 10(-13), 10(-9) and 10(-7) respectively). Finally, using an ensemble machine-learning tool, we discovered a unique 8-gene signature for this group of cancers that differentiates the group from the other tumor subsites of head and neck region. We investigated the role of promoter methylation in one of these genes, WIF1, and found no correlation between DNA methylation and down-regulation of WIF1. We validated our findings of gene expression, 8-gene signature and promoter methylation using q-PCR, data from TCGA and q-MSP respectively. Data presented in this manuscript has been submitted to the NCBI Geo database with the accession number GSE67994.", "claims": [{"id": "claim-method", "statement": "Normalization of the raw counts was done using the DESeq R package (R-3.1.0, DESeq-1.16.0) [76] and tested for differential expression with the following combinations: 1) all tumors vs their matched normal samples (referred as TN_P), 2) all tumor vs normal samples (matched & unmatched, TN_UP), and 3) pair-wise analyses for the individual tumor-normal pairs (T_P).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26413216", "locator": "sections[15] \"Differential gene expression analysis\" paragraph 2", "quote": "Normalization of the raw counts was done using the DESeq R package (R-3.1.0, DESeq-1.16.0) [76] and tested for differential expression with the following combinations: 1) all tumors vs their matched normal samples (referred as TN_P), 2) all tumor vs normal samples (matched & unmatched, TN_UP), and 3) pair-wise analyses for the individual tumor-normal pairs (T_P)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data presented in this manuscript has been submitted to the NCBI Geo database with the accession number GSE67994.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26413216", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Data presented in this manuscript has been submitted to the NCBI Geo database with the accession number GSE67994."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study used random-forest ensemble machine learning on sequencing-derived gene-expression data, with TCGA data used for validation, and identified an 8-gene signature distinguishing larynx and hypopharynx carcinoma from other head-and-neck tumor subsites.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:26413216", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Finally, using an ensemble machine-learning tool, we discovered a unique 8-gene signature for this group of cancers that differentiates the group from the other tumor subsites of head and neck region."}, {"asset": "source:pmid:26413216", "locator": "sections[1] \"INTRODUCTION\" paragraph 4", "quote": "We used computational pipeline with sequencing data from the discovery set to identify the significantly over- and under-expressed genes in SCCL and SCCHP."}, {"asset": "source:pmid:26413216", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We validated our findings of gene expression, 8-gene signature and promoter methylation using q-PCR, data from TCGA and q-MSP respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study used random-forest ensemble machine learning on sequencing-derived gene-expression data, with TCGA data used for validation, and identified an 8-gene signature distinguishing larynx and hypopharynx carcinoma from other head-and-neck tumor subsites.", "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:26413216"], "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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S: smoking, A: alcohol, C: chewing tobacco, N/A: not available", "structure": {"pmcid": "PMC4575920", "section_index": 10, "section_title": "Patient samples used in the study", "row_count": 15, "column_count": 9}, "table": {"label": "Table 1", "caption": "Sample details used in the study. S: smoking, A: alcohol, C: chewing tobacco, N/A: not available", "rows": [["Sample name", "Age", "Gender", "Subsite", "Habits", "TNM", "Stage"], ["S", "A", "C"], ["LP1", "70", "M", "Larynx", "Y", "Y", "N", "T3N0Mx", "III"], ["LP2", "68", "M", "Larynx", "Y", "N", "N", "T4N2bMx", "IVA"], ["LP3", "60", "M", "Larynx", "N", "N", "N", "T4N0Mx", "IVA"], ["LP4", "62", "M", "Larynx", "N", "N", "Y", "T4N2cMx", "IVA"], ["LP5", "64", "M", "Larynx", "N", "N", "N", "T1N0M0", "I"], ["LP6", "57", "F", "Pharynx", "N", "N", "N", "T2N0M0", "II"], ["LP7", "75", "M", "Larynx", "N", "N", "Y", "T4aN0Mx", "IVA"], ["LP8", "60", "M", "Larynx", "Y", "N", "Y", "T3N0M0", "III"], ["LP9", "40", "F", "Hypopharynx", "N", "N", "Y", "T3N0M0", "III"], ["LP10", "54", "M", "Hypopharynx", "Y", "N", "Y", "T3N0Mx", "III"], ["LP11", "46", "M", "Larynx", "N", "Y", "N", "T2N0M0", "II"], ["LP12", "65", "F", "Larynx", "N", "N", "N", "T4aN2cM0", "IVA"], ["LP13", "55", "M", "Hypopharynx", "N/A", "N/A", "N/A", "N/A", "IVA"]], "row_count": 15, "column_count": 9, "numeric_cells": 17, "header_rows": 2, "locator": "section[10]/table-wrap[1]#T1"}}], "gaps": ["asset:data:geo:GSE67994 not downloaded", "asset:data:geo:GSE67994 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "deseq2", "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": 1.0, "band": "verbatim", "quote": "Normalization of the raw counts was done using the DESeq R package (R-3.1.0, DESeq-1.16.0) [76] and tested for differential expression with the following combinations: 1) all tumors vs their matched normal samples (referred as TN_P), 2) all tumor vs normal samples (matched & unmatched, TN_UP), and 3) pair-wise analyses for the individual tumor-normal pairs (T_P)."}}], "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: deseq2."}, "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": ["GSE67994"], "resolved_accessions": ["GSE67994"], "statements": ["Data presented in this manuscript has been submitted to the NCBI Geo database with the accession number GSE67994."], "basis": "The paper names GSE67994 in NCBI 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:26413216", "data:geo:GSE67994", "asset:table:pmid:26413216:1", "asset:table:pmid:26413216:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE67994"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:25:24Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 8, "usage": {"prompt_tokens": 120554, "completion_tokens": 4326, "cached_tokens": 1840}}, "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:26413216", "type": "paper", "label": "pmid:26413216"}, {"id": "source:pmid:26413216", "type": "manuscript", "label": "PMID 26413216 full text"}, {"id": "data:geo:GSE67994", "type": "dataset", "label": "GEO GSE67994"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:26413216", "type": "paper", "label": "pmid:26413216"}, {"id": "source:pmid:26413216", "type": "manuscript", "label": "PMID 26413216 full text"}, {"id": "data:geo:GSE67994", "type": "dataset", "label": "GEO GSE67994"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-26413216", "type": "extraction", "used": ["source:pmid:26413216"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE67994", "type": "accession_resolution", "used": ["data:geo:GSE67994"], "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:26413216", "parent_hash": "sha256:4a4580b49ce3458411ff0ba239c69cfdc93d3822fb83598ecc3763185c3f9859", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE67994 licence not read", "asset:data:geo:GSE67994 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["validation in additional tumors. We designed qPCR primers (Supplementary Table 2) and measured", "ynx and hypopharynx tumors Quantitative PCR (qPCR) validation of gene expression changes, Red:"], "order_basis": "paper_text_order:3190", "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": ["Normalization of the raw counts was done using the DESeq R package (R-3.1.0, DESeq-1.16.0) [76] and tested for differential expression with the following combinations: 1) all tumors vs their matched normal samples (referred as TN_P), 2) all tumor vs normal samples (matched & unmatched, TN_UP), and 3) pair-wise analyses for the individual tumor-normal pairs (T_P)."], "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":"2026-11-04T01:42:26+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}}}