{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31410310", "kind": "science-record", "revision": 8, "content_hash": "sha256:2635e6ad26902e5fa7467bec8e95329b8b2804249786a841464aa14eab21ffed", "created_at": "2026-11-01T15:40:48Z", "updated_at": "2026-11-01T22:44:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of crucial genes based on expression profiles of hepatocellular carcinomas by bioinformatics analysis.", "doi": "10.7717/peerj.7436", "pmid": "31410310", "authors": ["Ze-Kun Liu", "Ren-Yu Zhang", "Yu-Le Yong", "Zhi-Yun Zhang", "Can Li", "Zhi-Nan Chen", "Huijie Bian"], "journal": "PeerJ", "year": 2019, "abstract": "Hepatocellular carcinoma (HCC) is one of the most heterogeneous malignant cancers with no effective targets and treatments. However, the molecular pathogenesis of HCC remains largely uncertain. The aims of our study were to find crucial genes involved in HCC through multidimensional methods and revealed potential molecular mechanisms. Here, we reported the gene expression profile GSE121248 findings from 70 HCC and 37 adjacent normal tissues, all of which had chronic hepatitis B virus (HBV) infection, we were seeking to identify the dysregulated pathways, crucial genes and therapeutic targets implicated in HBV-associated HCC. We found 164 differentially expressed genes (DEGs) (92 downregulated genes and 72 upregulated genes). Gene ontology (GO) analysis of DEGs revealed significant functional enrichment of mitotic nuclear division, cell division, and the epoxygenase P450 pathway. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were mainly enriched in metabolism, cell cycle regulation and the p53 signaling pathway. The Mcode plugin was calculated to construct a module complex of DEGs, and the module was mainly enriched in cell cycle checkpoints, RHO GTPase effectors and cytochrome P450. Considering a weak contribution of each gene, gene set enrichment analysis (GSEA) was performed, revealing results consistent with those described above. Six crucial proteins were selected based on the degree of centrality, including NDC80, ESR1, ZWINT, NCAPG, ENO3 and CENPF. Real-time quantitative PCR analysis validated the six crucial genes had the same expression trend as predicted. Furthermore, the methylation data of The Cancer Genome Atlas (TCGA) with HCC showed that mRNA expression of crucial genes was negatively correlated with methylation levels of their promoter region. The overall survival reflected that high expression of NDC80, CENPF, ZWINT, and NCAPG significantly predicted poor prognosis, whereas ESR1 high expression exhibited a favorable prognosis. The identification of the crucial genes and pathways would contribute to the development of novel molecular targets and biomarker-driven treatments for HCC.", "claims": [{"id": "claim-method", "statement": "The t test methods of the limma package (version 3.38.2, http://bioconductor.org/packages/limma/) (Ritchie et al., 2015) were used to identify DEGs in HCC tissues compared to adjacent normal tissues.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31410310", "locator": "sections[4] \"Data processing and identification of DEGs\" paragraph 2", "quote": "The t test methods of the limma package (version 3.38.2, http://bioconductor.org/packages/limma/) (Ritchie et al., 2015) were used to identify DEGs in HCC tissues compared to adjacent normal tissues."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nThe raw measurements are available in the Supplemental Tables.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31410310", "locator": "sections[33] \"Data Availability Statement\" paragraphs 1-3", "quote": "The following information was supplied regarding data availability:\nThe raw measurements are available in the Supplemental Tables."}], "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:31410310"], "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:GSE121248"], "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:GSE121248"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31410310", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.7436", "sha256": 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false, "licence_read": false}}, {"id": "asset:table:pmid:31410310:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:840b388db0123ec9e7e961560d37a1047657567d86ded4146165ab9ea0cbf306", "bytes": 1459, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#table-1", "version": null, "note": "The top 10 proteins ranked based on the node centrality of the PPI network.", "structure": {"pmcid": "PMC6689388", "section_index": 14, "section_title": "Protein–protein interaction network of DEGs", "row_count": 12, "column_count": 9}, "table": {"label": "Table 1", "caption": "The top 10 proteins ranked based on the node centrality of the PPI network.", "rows": [["Rank", "Degree centrality", "Betweenness centrality", "Closeness centrality", "Eigenvector centrality"], ["", "Gene symbol", "Expression in HCC", "Gene symbol", "Expression in HCC", "Gene 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"up-regulated", "BUB1B", "up-regulated"], ["10", "NCAPG", "up-regulated", "ENO3", "down-regulated", "NEK2", "up-regulated", "MAD2L1", "up-regulated"]], "row_count": 12, "column_count": 9, "numeric_cells": 14, "header_rows": 2, "locator": "section[14]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:31410310:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:93bdb1d7a555c3bbcac7e618665231194274b3e868749be5a4680c77d2aaef58", "bytes": 1503, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#table-2", "version": null, "note": "Validation of the relationship between methylation and mRNA expression of crucial genes in TCGA.", "structure": {"pmcid": "PMC6689388", "section_index": 16, "section_title": "Validation of mRNA expression of crucial genes", "row_count": 21, "column_count": 7}, "table": {"label": "Table 2", "caption": "Validation of the relationship between methylation and mRNA expression of crucial genes in TCGA.", "rows": [["Crucial gene", "mRNA expression in HCC", "Methylation status in HCC"], ["", "mRNA expression", "P-value", "Methylation", "Position", "Pearson correlation", "P-value"], ["NDC80", "High expression", "<2.2E-16", "Hypomethylation", "chr18:2571606", "−0.150", "1.64E-03"], ["chr18:2571747", "−0.282", "<2.2E-16"], ["ZWINT", "High expression", "<2.2E-16", "Hypomethylation", "chr10:58121299", "−0.142", "0.03"], ["NCAPG", "High expression", "<2.2E-16", "Hypomethylation", "chr4:17812759", "−0.236", "2.26E-11"], ["chr4:17813558", "−0.544", "<2.2E-16"], ["CENPF", "High expression", "<2.2E-16", "Hypomethylation", "chr1:214776904", "−0.243", "1.48E-12"], ["chr1:214777596", "−0.304", "1.60E-14"], ["chr1:214780880", "−0.174", "6.27E-11"], ["chr1:214781456", "−0.154", "1.38E-04"], ["chr1:214781663", "−0.217", "1.21E-05"], ["chr1:214788192", "−0.150", "7.40E-07"], ["ESR1", "Low expression", 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:31410310", "data:geo:GSE121248", "asset:table:pmid:31410310:1", "asset:table:pmid:31410310:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE121248"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:15:49Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 40474, "completion_tokens": 2082, "cached_tokens": 776}}, "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:31410310", "type": "paper", "label": "pmid:31410310"}, {"id": "source:pmid:31410310", "type": "manuscript", "label": "PMID 31410310 full text"}, {"id": "data:geo:GSE121248", "type": "dataset", "label": "GEO GSE121248"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:31410310", "type": "paper", "label": "pmid:31410310"}, {"id": "source:pmid:31410310", "type": "manuscript", "label": "PMID 31410310 full text"}, {"id": "data:geo:GSE121248", "type": "dataset", "label": "GEO GSE121248"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-31410310", "type": "extraction", "used": ["source:pmid:31410310"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE121248", "type": "accession_resolution", "used": ["data:geo:GSE121248"], "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:31410310", "parent_hash": "sha256:5ed45ec4d64a28334ddf755a4b3cae35cc11e683e4c4bdf619761869e7eaae82", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE121248 licence not read", "asset:data:geo:GSE121248 not downloaded", "asset:data:geo:GSE22058 licence not read", "asset:data:geo:GSE22058 not downloaded", "asset:data:geo:GSE25097 licence not read", "asset:data:geo:GSE25097 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "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": ["g NDC80, ESR1, ZWINT, NCAPG, ENO3 and CENPF. Real-time quantitative PCR analysis validated the six crucial genes had", "II (TaKaRaBio, Otsu, Japan) and primers, and qPCR data were analyzed using △△Ct method with β-"], "order_basis": "paper_text_order:1583", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["atlas.org) was used for protein detection by immunohistochemistry. 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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":"2026-11-04T01:25:52+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}}}