{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34039311", "kind": "science-record", "revision": 7, "content_hash": "sha256:0794444d2e99b3d8de6814693e2081cab4a309e588a2179f4dedd54548d4de10", "created_at": "2026-11-01T15:41:36Z", "updated_at": "2026-11-01T22:03:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of significant genes as prognostic markers and potential tumor suppressors in lung adenocarcinoma via bioinformatical analysis.", "doi": "10.1186/s12885-021-08308-3", "pmid": "34039311", "authors": ["Mingze Lu", "Xiaowen Fan", "Weilin Liao", "Yijiao Li", "Lijie Ma", "Mu Yuan", "Rui Gu", "Zhengdao Wei", "Chao Wang", "Hua Zhang"], "journal": "BMC cancer", "year": 2021, "abstract": "BACKGROUND: Lung adenocarcinoma (LAC) is the predominant histologic subtype of lung cancer and has a complicated pathogenesis with high mortality. The purpose of this study was to identify differentially expressed genes (DEGs) with prognostic value and determine their underlying mechanisms.\nMETHODS: Gene expression data of GSE27262 and GSE118370 were acquired from the Gene Expression Omnibus database, enrolling 31 LAC and 31 normal tissues. Common DEGs between LAC and normal tissues were identified using the GEO2R tool and Venn diagram software. Next, the Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to analyze the Gene Ontology and Kyoto Encyclopedia of Gene and Genome (KEGG) pathways. Then, protein-protein interaction (PPI) network of DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes and central genes were identified via Molecular Complex Detection. Furthermore, the expression and prognostic information of central genes were validated via Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier analysis, respectively. Finally, DAVID, real-time PCR and immunohistochemistry were applied to re-analyze the identified genes, which were also further validated in two additional datasets from ArrayExpress database.\nRESULTS: First, 189 common DEGs were identified among the two datasets, including 162 downregulated and 27 upregulated genes. Next, Gene Ontology and KEGG pathway analysis of the DEGs were conducted through DAVID. Then, PPI network of DEGs was constructed and 17 downregulated central genes were identified. Furthermore, the 17 downregulated central genes were validated via GEPIA and datasets from ArrayExpress, and 12 of them showed a significantly better prognosis. Finally, six genes were identified significantly enriched in neuroactive ligand-receptor interactions (EDNRB, RXFP1, P2RY1, CALCRL) and Rap1 signaling pathway (TEK, P2RY1, ANGPT1) via DAVID, which were further validated to be weakly expressed in LAC tissues via RNA quantification and immunohistochemistry analysis.\nCONCLUSIONS: The low expression pattern and relation to prognosis indicated that the six genes were potential tumor suppressor genes in LAC. In conclusion, we identified six significantly downregulated DEGs as prognostic markers and potential tumor suppressor genes in LAC based on integrated bioinformatics methods, which could act as potential molecular markers and therapeutic targets for LAC patients.", "claims": [{"id": "claim-method", "statement": "Survival analysis was conducted using the Kaplan-Meier plotter, and the log-rank P value and hazard ratio (HR) with 95% confidence intervals were computed and shown on the plot [20].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34039311", "locator": "sections[7] \"Survival and RNA sequencing analysis\" paragraph 2", "quote": "Survival analysis was conducted using the Kaplan-Meier plotter, and the log-rank P value and hazard ratio (HR) with 95% confidence intervals were computed and shown on the plot [20]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Dataset supporting our findings is available, at the following website: www.ncbi.nlm.nih.gov/geo/, www.ebi.ac.uk/arrayexpress/. All data generated or analyzed during this study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34039311", "locator": "sections[24] \"Availability of data and materials\" paragraph 2", "quote": "Dataset supporting our findings is available, at the following website: www.ncbi.nlm.nih.gov/geo/, www.ebi.ac.uk/arrayexpress/. All data generated or analyzed during this study are available from the corresponding author on reasonable request."}], "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:34039311"], "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:GSE118370"], "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:GSE118370"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34039311", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-021-08308-3", "sha256": "sha256:723cf15b4449c8292196e863e1fe619e75cf3b7d886f594ab62bb12cb55eba51", "bytes": 44424, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-021-08308-3", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8157630", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE118370", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE118370", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE118370", "version": null, "note": "Dataset supporting our findings is available, at the following website: www.ncbi.nlm.nih.gov/geo/, www.ebi.ac.uk/arrayexpress/. All data generated or analyzed during this study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Dataset supporting our findings is available, at the following website: www.ncbi.nlm.nih.gov/geo/, www.ebi.ac.uk/arrayexpress/. All data generated or analyzed during this study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3325818", "GSM3325819", "GSM3325820", "GSM3325821", "GSM3325822", "GSM3325823", "GSM3325824", "GSM3325825", "GSM3325826", "GSM3325827", "GSM3325828", "GSM3325829"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data from lung adenocarcinoma tissues and paired normal lung tissues", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE27262", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27262", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE27262", "version": null, "note": "Dataset supporting our findings is available, at the following website: www.ncbi.nlm.nih.gov/geo/, www.ebi.ac.uk/arrayexpress/. All data generated or analyzed during this study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Dataset supporting our findings is available, at the following website: www.ncbi.nlm.nih.gov/geo/, www.ebi.ac.uk/arrayexpress/. All data generated or analyzed during this study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM673870", "GSM673871", "GSM673872", "GSM673873", "GSM673874", "GSM673875", "GSM673876", "GSM673877", "GSM673878", "GSM673879", "GSM673880", "GSM673881", "GSM673882", "GSM673883", "GSM673884", "GSM673885", "GSM673886", "GSM673887", "GSM673888", "GSM673889", "GSM673890", "GSM673891", "GSM673892", "GSM673893", "GSM673894", "GSM673895", "GSM673896", "GSM673897", "GSM673898", "GSM673899", "GSM673900", "GSM673901", "GSM673902", "GSM673903", "GSM673904", "GSM673905", "GSM673906", "GSM673907", "GSM673908", "GSM673909", "GSM673910", "GSM673911", "GSM673912", "GSM673913", "GSM673914", "GSM673915", "GSM673916", "GSM673917", "GSM673918", "GSM673919"], "sample_count": 50, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression profiling of Non-small cell lung cancer in Taiwan", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34039311:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:63b0087bde075d0f7a78a523c538fcb6f227e8cc2f4fd62d4862a9c4f1ee8007", "bytes": 1641, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#Tab1", "version": null, "note": "All 189 common differentially expressed genes (DEGs) were identified from two profile datasets, including 162 downregulated genes and 27 upregulated genes in lung adenocarcinoma tissues compared to normal lung tissues", "structure": {"pmcid": "PMC8157630", "section_index": 11, "section_title": "Identification of DEGs in lung adenocarcinoma", "row_count": 3, "column_count": 2}, "table": {"label": "Table 1", "caption": "All 189 common differentially expressed genes (DEGs) were identified from two profile datasets, including 162 downregulated genes and 27 upregulated genes in lung adenocarcinoma tissues compared to normal lung tissues", "rows": [["DEGs", "Gene Name"], ["Downregulated", "HBA2///HBA1 ACE SCN7A FMO2 RTKN2 EMCN SLC19A3 HSPB6 SOX7 MYZAP ADARB1 AOC3 CCM2L SFTPC PPP1R14A FRMD3 P2RY1 WISP2 MFAP4 KCNT2 SVEP1 TTN SEMA3G ERG SLC6A4 PECAM1 TCF21 TGFBR3 KCNK3 HHIP ADH1B ARHGEF26 SH3GL3 ARHGAP6 GIMAP8 SCARA5 NFASC LINC00968 ASPA BTNL9 PCAT19 NDRG4 FABP4 IGSF10 EDNRB ACVRL1 GPC3 FCN3 CDO1 MYCT1 LIN7A KANK3 SDPR TEK GRIA1 STX11 LINC00312 GRK5 FAM107A CCDC85A DACH1 VGLL3 EML1 CCBE1 GPX3 AGER GUCY1A2 GHR PALM2-AKAP2///AKAP2 ANXA8L1///ANXA8 SOX17 STXBP6 RGCC VWF PDE8B S1PR1 SEMA5A GIMAP1 CD300LG ABI3BP CD93 TIE1 EMP2 LYVE1 KIAA1462 VIPR1 LEPROT///LEPR SLC5A9 SH2D3C CYYR1 STARD13 EPAS1 RAMP3 CLIC5 SPOCK2 KL AKAP12 CD36 SLIT2 TRHDE FGFR4 FHL5 PDE5A ADGRL3 MME LDB2 SHANK3 ROBO4 SPTBN1 CALCRL SLC14A1 TMTC1 CAV1 CLEC1A RXFP1 SMAD9 RASIP1 SGCG PPBP JAM2 TBX3 PTPRB AFAP1L1 QKI FOXF1 ACADL SEMA6D CLDN18 ADGRL2 ANKRD29 FENDRR AQP4 PIR-FIGF///FIGF CDH5 HEG1 PDK4 GPM6A ITGA8 COL6A6 TNNC1 IL1RL1 ECSCR ANGPT1 ADRA1A SMAD6 DPP6 FAT3 SEMA6A MCEMP1 HBB LOC100996760 NTNG1 GNG11 FHL1 RHOJ TMEM100 SSTR1 DUOX1 KLF4 TRDV3 GNLY KLRF1"], ["Upregulated", "KIF26B SPINK1 SGPP2 GDF15 MMP7 C1orf53 TMEM45B TOX3 GJB2 AFAP1-AS1 PROM2 CD24 ABCC3 TMPRSS4 HS6ST2 CP SERPIND1 BLACAT1 MMP1 NEK2 CLIC6 HABP2 WFDC2 SIX1 TFAP2A AGR2 COL10A1"]], "row_count": 3, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[11]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:34039311:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:48a7dbc8f374b529b805b4aaf4d98a7bac8c3251eb2630d9624f85dcc504aeec", "bytes": 2489, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab2", "version": null, "note": "Gene Ontology analysis of differentially expressed genes in lung adenocarcinoma", "structure": {"pmcid": "PMC8157630", "section_index": 12, "section_title": "Gene ontology and KEGG analysis of DEGs in lung adenocarcinoma", "row_count": 24, "column_count": 7}, "table": {"label": "Table 2", "caption": "Gene Ontology analysis of differentially expressed genes in lung adenocarcinoma", "rows": [["Expression", "Category", "Term", "Count", "%", "p-Value", "FDR"], ["Downregulated", "GOTERM_BP_DIRECT", "GO:0001525 ~ angiogenesis", "10", "6.2", "3.06E-07", "4.71E-04"], ["GOTERM_BP_DIRECT", "GO:0001570 ~ vasculogenesis", "7", "4.3", "3.34E-06", "0.005135"], ["GOTERM_BP_DIRECT", "GO:0007165 ~ signal transduction", "12", "7.4", "1.26E-04", "0.193754"], ["GOTERM_BP_DIRECT", "GO:0031623 ~ receptor internalization", "5", "3.1", "1.45E-04", "0.222577"], ["GOTERM_BP_DIRECT", "GO:0001755 ~ neural crest cell migration", "5", "3.1", "3.69E-04", "0.566138"], ["GOTERM_CC_DIRECT", "GO:0016021 ~ integral component of membrane", "49", "30.3", "1.48E-04", "0.16707"], ["GOTERM_CC_DIRECT", "GO:0005886 ~ plasma membrane", "25", "15.4", "8.82E-04", "0.993318"], ["GOTERM_CC_DIRECT", "GO:0005578 ~ proteinaceous extracellular matrix", "6", "3.7", "0.008111", "8.80424"], ["GOTERM_CC_DIRECT", "GO:0005911 ~ cell-cell junction", "4", "2.5", "0.047922", "42.63677"], ["GOTERM_MF_DIRECT", "GO:0030215 ~ semaphorin receptor binding", "4", "2.5", "2.31E-04", "0.280668"], ["GOTERM_MF_DIRECT", "GO:0045499 ~ chemorepellent activity", "4", "2.5", "8.56E-04", "1.037711"], ["GOTERM_MF_DIRECT", "GO:0008201 ~ heparin binding", "4", "2.5", "0.040365", "39.47803"], ["Upregulated", "GOTERM_BP_DIRECT", "GO:0030574 ~ collagen catabolic process", "3", "11.1", "0.003145", "3.886365"], ["GOTERM_BP_DIRECT", "GO:0006508 ~ proteolysis", "5", "18.5", "0.003709", "4.568267"], ["GOTERM_BP_DIRECT", "GO:0007605 ~ sensory perception of sound", "3", "11.1", "0.012967", "15.14675"], ["GOTERM_BP_DIRECT", "GO:0048701 ~ embryonic cranial skeleton morphogenesis", "2", "7.4", "0.039861", "40.06517"], ["GOTERM_CC_DIRECT", "GO:0005615 ~ extracellular space", "8", "29.6", "0.001014", "0.992618"], ["GOTERM_CC_DIRECT", "GO:0005576 ~ extracellular region", "8", "29.6", "0.002863", "2.780239"], ["GOTERM_CC_DIRECT", "GO:0070062 ~ extracellular exosome", "9", "33.3", "0.017782", "16.17818"], ["GOTERM_CC_DIRECT", "GO:0005578 ~ proteinaceous extracellular matrix", "3", "11.1", "0.044503", "36.09452"], ["GOTERM_MF_DIRECT", "GO:0004866 ~ endopeptidase inhibitor activity", "3", "11.1", "0.001227", "1.243792"], ["GOTERM_MF_DIRECT", "GO:0004252 ~ serine-type endopeptidase activity", "4", "14.8", "0.004242", "4.240205"], ["GOTERM_MF_DIRECT", "GO:0004867 ~ serine-type endopeptidase inhibitor activity", "3", "11.1", "0.007004", "6.913304"]], "row_count": 24, "column_count": 7, "numeric_cells": 115, "header_rows": 1, "locator": "section[12]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:34039311:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cecc1b4f7fff213071b29bc7a445c933be5a4f4cf7d97e72d091bee737892d82", "bytes": 873, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#Tab3", "version": null, "note": "KEGG pathway analysis of differentially expressed genes (downregulated) in lung adenocarcinoma", "structure": {"pmcid": "PMC8157630", "section_index": 12, "section_title": "Gene ontology and KEGG analysis of DEGs in lung adenocarcinoma", "row_count": 6, "column_count": 6}, "table": {"label": "Table 3", "caption": "KEGG pathway analysis of differentially expressed genes (downregulated) in lung adenocarcinoma", "rows": [["Pathway ID", "Name", "Count", "%", "p-Value", "Genes"], ["ptr04080", "Neuroactive ligand-receptor interaction", "10", "6.2", "0.001298", "EDNRB, S1PR1, RXFP1, GRIA1, SSTR1, P2RY1, ADRA1A, CALCRL, VIPR1, GHR"], ["ptr04514", "Cell adhesion molecules (CAMs)", "7", "4.3", "0.003249", "CLDN18, ITGA8, PECAM1, NTNG1, NFASC, JAM2, CDH5"], ["ptr04360", "Axon guidance", "6", "3.7", "0.008075", "SEMA5A, SEMA6A, SEMA6D, SEMA3G, NTNG1, SLIT2"], ["ptr05410", "Hypertrophic cardiomyopathy (HCM)", "5", "3.1", "0.009096", "ACE, SGCG, TNNC1, ITGA8, TTN"], ["ptr04270", "Vascular smooth muscle contraction", "5", "3.1", "0.033494", "RAMP3, GUCY1A2, ADRA1A, CALCRL, PPP1R14A"]], "row_count": 6, "column_count": 6, "numeric_cells": 22, "header_rows": 1, "locator": "section[12]/table-wrap[2]#Tab3"}}, {"id": "asset:table:pmid:34039311:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:368d86166e166c0acddda7090aba9c84b7b1cbeea8857fd70c36ad62d3f3272e", "bytes": 363, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#Tab4", "version": null, "note": "Validation of the 17 central genes using GEPIA", "structure": {"pmcid": "PMC8157630", "section_index": 14, "section_title": "Analysis of 17 core genes via the GEPIA and Kaplan-Meier plotter", "row_count": 2, "column_count": 2}, "table": {"label": "Table 4", "caption": "Validation of the 17 central genes using GEPIA", "rows": [["Category", "Genes"], ["Genes with low expression in LAC (P<0.05)", "ADRA1A VWF VIPR1 TIE1 ROBO4 GRK5 TEK PECAM1 LYVE1 RXFP1 CALCRL ANGPT1 EDNRB RAMP3 CDH5 PTPRB P2RY1"]], "row_count": 2, "column_count": 2, "numeric_cells": 1, "header_rows": 1, "locator": "section[14]/table-wrap[1]#Tab4"}}, {"id": "asset:table:pmid:34039311:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b7a19333d9dc47c4f3ad2d51e5c3c9fbd5a5b850f52c0cdac43023ce8e693411", "bytes": 485, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[2]#Tab5", "version": null, "note": "Prognostic information of the 17 key candidate genes", "structure": {"pmcid": "PMC8157630", "section_index": 14, "section_title": "Analysis of 17 core genes via the GEPIA and Kaplan-Meier plotter", "row_count": 4, "column_count": 2}, "table": {"label": "Table 5", "caption": "Prognostic information of the 17 key candidate genes", "rows": [["Category", "Genes"], ["Genes with significantly better survival (P <0.05)", "VWF ROBO4 GRK5 TEK PECAM1 RXFP1 CALCRL ANGPT1 EDNRB CDH5 PTPRB P2RY1"], ["Genes with significantly worse survival (P <0.05)", "ADRA1A TIE1 LYVE1"], ["Genes without significant survival (P >0.05)", "VIPR1 RAMP3"]], "row_count": 4, "column_count": 2, "numeric_cells": 3, "header_rows": 1, "locator": "section[14]/table-wrap[2]#Tab5"}}, {"id": "asset:table:pmid:34039311:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:98d79d135725c9ef225b36a8faffe3cbd523d75378dfe9f598dbcd3f5f88e89c", "bytes": 448, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#Tab6", "version": null, "note": "Re-analysis of the 12 selected genes via KEGG pathway enrichment", "structure": {"pmcid": "PMC8157630", "section_index": 15, "section_title": "Re-analysis of 12 core genes by KEGG, RNA quantification and immunohistochemistry", "row_count": 3, "column_count": 6}, "table": {"label": "Table 6", "caption": "Re-analysis of the 12 selected genes via KEGG pathway enrichment", "rows": [["Pathway ID", "Name", "Count", "%", "p-Value", "Genes"], ["cfa04080", "Neuroactive ligand-receptor interaction", "4", "33.3", "0.005724", "EDNRB RXFP1 P2RY1 CALCRL"], ["cfa04015", "Rap1 signaling pathway", "3", "25.0", "0.035813", "TEK P2RY1 ANGPT1"]], "row_count": 3, "column_count": 6, "numeric_cells": 8, "header_rows": 1, "locator": "section[15]/table-wrap[1]#Tab6"}}], "gaps": ["asset:data:geo:GSE118370 not downloaded", "asset:data:geo:GSE118370 licence not read", "asset:data:geo:GSE27262 not downloaded", "asset:data:geo:GSE27262 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Survival analysis was conducted using the Kaplan-Meier plotter, and the log-rank P value and hazard ratio (HR) with 95% confidence intervals were computed and shown on the plot [20]."}}, {"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": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {"hazard_ratio": "he log-rank P value and hazard ratio (HR) with 95% confidenc", "p_value": "otter, and the log-rank P value and hazard ratio (HR) w"}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-4", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {"log2fc_threshold": "mal lung specimen with |log2FC| > 2 and an adjusted P"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-5", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-6", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}, {"id": "method-7", "family": "network_analysis", "specific": "centrality", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "centrality"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": ["GSE27262", "GSE118370"], "resolved_accessions": ["GSE27262", "GSE118370"], "statements": ["Dataset supporting our findings is available, at the following website: www.ncbi.nlm.nih.gov/geo/, www.ebi.ac.uk/arrayexpress/. All data generated or analyzed during this study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE27262, GSE118370 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:34039311", "data:geo:GSE118370", "asset:table:pmid:34039311:1", "asset:table:pmid:34039311:2", "asset:table:pmid:34039311:3", "asset:table:pmid:34039311:4", "asset:table:pmid:34039311:5", "asset:table:pmid:34039311:6"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE118370"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:30:28Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 36667, "completion_tokens": 2813, "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:34039311", "type": "paper", "label": "pmid:34039311"}, {"id": "source:pmid:34039311", "type": "manuscript", "label": "PMID 34039311 full text"}, {"id": "data:geo:GSE118370", "type": "dataset", "label": "GEO GSE118370"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34039311", "type": "paper", "label": "pmid:34039311"}, {"id": "source:pmid:34039311", "type": "manuscript", "label": "PMID 34039311 full text"}, {"id": "data:geo:GSE118370", "type": "dataset", "label": "GEO GSE118370"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34039311", "type": "extraction", "used": ["source:pmid:34039311"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE118370", "type": "accession_resolution", "used": ["data:geo:GSE118370"], "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:34039311", "parent_hash": "sha256:22af5fa795e22aed072f51829cca8061639c1f9549eb72e8cc6874ed9ffcac0b", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE118370 licence not read", "asset:data:geo:GSE118370 not downloaded", "asset:data:geo:GSE27262 licence not read", "asset:data:geo:GSE27262 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": ["eier analysis, respectively. Finally, DAVID, real-time PCR and immunohistochemistry were applied to re-", "LAC patients, six genes were re-analyzed via real-time PCR (a) and immunohistochemistry (b) analysis. R", "f IHC staining were shown. Scale bar, 50 μm. Real-time PCR data were presented as mean ± SEM and the di"], "order_basis": "paper_text_order:1240", "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": 0.99, "evidence": ["pectively. Finally, DAVID, real-time PCR and immunohistochemistry were applied to re-analyze the identified ge", "ed in LAC tissues via RNA quantification and immunohistochemistry analysis. CONCLUSIONS: The low expression pa", "2 core genes by KEGG, RNA quantification and immunohistochemistry To figure out the possible pathway of the 12", "mal lung specimens by RNA quantification and immunohistochemistry analysis. Results showed that all six genes"], "order_basis": "paper_text_order:1258", "id": "assay:2"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["of DEGs Robust multi-array average (RMA) and MicroArray Suite (MAS) approach was performed for backg"], "order_basis": "paper_text_order:2677", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Survival analysis was conducted using the Kaplan-Meier plotter, and the log-rank P value and hazard ratio (HR) with 95% confidence intervals were computed and shown on the plot [20]."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]},"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":"2026-11-04T04:17:06+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}}}