{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34527340", "kind": "science-record", "revision": 8, "content_hash": "sha256:e3870111eb1c73093078222bdcf3a603d249732d620172e3e059a4f6ff5b86c7", "created_at": "2026-11-01T15:41:52Z", "updated_at": "2026-11-01T22:04:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Screening and evaluation of the role of immune genes of brain metastasis in lung adenocarcinoma progression based on the TCGA and GEO databases.", "doi": "10.21037/jtd-21-935", "pmid": "34527340", "authors": ["Cheng Chen", "Qiang Guo", "Yang Tang", "Wendong Qu", "Jiebin Zuo", "Xixian Ke", "Yongxiang Song"], "journal": "Journal of thoracic disease", "year": 2021, "abstract": "BACKGROUND: Brain metastasis was one of the factors leading to the poor long-term prognosis of patients with lung adenocarcinoma (LUAD).\nMETHODS: The expression levels of immune genes in LUAD and LUAD brain metastases tissues were analyzed in GSE161116 dataset using the GEO2R, and the levels of differential immune genes in normal lung and LUAD tissues were verified. The biological functions and signaling mechanisms of the differential immune genes were explored via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Cox regression analysis was used to screen the prognostic factors of LUAD patients, and a risk model was constructed. The role of the model was checked in the development of LUAD via receiver operating characteristic analysis, gene set enrichment analysis, and Cox regression analysis.\nRESULTS: Differentially expressed genes (DEGs) in brain metastasis were involved in the adaptive immune response, B cell differentiation, leukocyte migration, NF-kB signaling pathway, among others. The expression levels of TNFRSF11A, MS4A2, IL11, CAMP, MS4A1, and F2RL1 were independent factors affecting the poor prognosis of LUAD patients via Cox regression analysis and Akaike information criterion. In the constructed risk model, the overall survival of LUAD patients in the high-risk group was poor. The risk model was significantly related to the gender, clinical stage, T stage, lymph node metastasis, and survival status of LUAD patients. In addition, the risk model score was an independent risk factor that affected the poor prognosis of LUAD patients. TNFRSF11A, CAMP, F2RL1, IL11, MS4A1, and MS4A2 of the risk factors had diagnostic significance in LUAD brain metastasis and LUAD. The risk model participated in cytokinetic process, cell cycle, citrate cycle TCA cycle, etc. The risk model score was correlated with the levels of B cells memory, mast cells resting, macrophages M0, mast cells activated, neutrophils, eosinophils, T cells gamma delta, and immune cell markers.\nCONCLUSIONS: The risk model based on the LUAD brain metastasis immune factors TNFRSF11A, MS4A2, IL11, CAMP, MS4A1, and F2RL1 was related to the diagnosis, poor prognosis, and immune infiltrating cells of LUAD patients, and is expected to provide a reference for the development of treatment strategies for LUAD patients.", "claims": [{"id": "claim-method", "statement": "K-M survival analysis of the GSE31210 and Jacob-00182-UM datasets showed that the expression levels of TNFRSF11A and MS4A2 were significantly correlated with the OS and relapse free survival (RFS) in LUAD patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34527340", "locator": "sections[17] \"The role of independent prognostic gene expression levels in the progression of LUAD\" paragraph 2", "quote": "K-M survival analysis of the GSE31210 and Jacob-00182-UM datasets showed that the expression levels of TNFRSF11A and MS4A2 were significantly correlated with the OS and relapse free survival (RFS) in LUAD patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "There were 9 LUAD and LUAD brain metastases tissues in the Gene Expression Omnibus (GEO) database GSE161116 dataset (Figure S1A). Among them, there were 10 EGFR mutant and 8 wild-type patients (Figure S1B,C). There were 11 female patients and 7 male patients (Figure S1D). The GEO GSE161116 dataset of 9 LUAD and 9 LUAD brain metastasis samples and GPL19965 annotation information were downloaded, and the expression levels of the prognostic genes were analyzed in LUAD and LUAD brain metastasis tissues by gender and EGFR mutation groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34527340", "locator": "sections[3] \"Differentially expressed immune genes\" paragraph 2", "quote": "There were 9 LUAD and LUAD brain metastases tissues in the Gene Expression Omnibus (GEO) database GSE161116 dataset (Figure S1A)."}, {"asset": "source:pmid:34527340", "locator": "sections[3] \"Differentially expressed immune genes\" paragraph 2", "quote": "Among them, there were 10 EGFR mutant and 8 wild-type patients (Figure S1B,C)."}, {"asset": "source:pmid:34527340", "locator": "sections[3] \"Differentially expressed immune genes\" paragraph 2", "quote": "There were 11 female patients and 7 male patients (Figure S1D)."}, {"asset": "source:pmid:34527340", "locator": "sections[7] \"Identification of independent prognostic genes\" paragraph 2", "quote": "The GEO GSE161116 dataset of 9 LUAD and 9 LUAD brain metastasis samples and GPL19965 annotation information were downloaded, and the expression levels of the prognostic genes were analyzed in LUAD and LUAD brain metastasis tissues by gender and EGFR mutation groups."}], "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:34527340"], "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:GSE13213"], "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:GSE13213"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34527340", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/jtd-21-935", "sha256": "sha256:11b054516b958495490c95d27f77a6f87f19b7bfa635c6c2c7180d9b5613251f", "bytes": 38576, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/jtd-21-935", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8411151", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE13213", "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=GSE13213", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE13213", "version": null, "note": "There were 9 LUAD and LUAD brain metastases tissues in the Gene Expression Omnibus (GEO) database GSE161116 dataset (Figure S1A). Among them, there were 10 EGFR mutant and 8 wild-type patients (Figure S1B,C). There were 11 female patients and 7 male patients (Figure S1D). The GEO GSE161116 dataset of 9 LUAD and 9 LUAD brain metastasis samples and GPL19965 annotation information were downloaded, and the expression levels of the prognostic genes were analyzed in LUAD and LUAD brain metastasis tissues by gender and EGFR mutation groups.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "There were 9 LUAD and LUAD brain metastases tissues in the Gene Expression Omnibus (GEO) database GSE161116 dataset (Figure S1A). Among them, there were 10 EGFR mutant and 8 wild-type patients (Figure S1B,C). There were 11 female patients and 7 male patients (Figure S1D). The GEO GSE161116 dataset of 9 LUAD and 9 LUAD brain metastasis samples and GPL19965 annotation information were downloaded, and the expression levels of the prognostic genes were analyzed in LUAD and LUAD brain metastasis tissues by gender and EGFR mutation groups.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM333673", "GSM333674", "GSM333675", "GSM333676", "GSM333677", "GSM333678", "GSM333679", "GSM333680", "GSM333681", "GSM333682", "GSM333683", "GSM333684", "GSM333685", "GSM333686", "GSM333687", "GSM333688", "GSM333689", "GSM333690", "GSM333691", "GSM333692", "GSM333693", "GSM333694", "GSM333695", "GSM333696", "GSM333697", "GSM333698", "GSM333699", "GSM333700", "GSM333701", "GSM333702", "GSM333703", "GSM333704", "GSM333705", "GSM333706", "GSM333707", "GSM333708", "GSM333709", "GSM333710", "GSM333711", "GSM333712", "GSM333713", "GSM333714", "GSM333715", "GSM333716", "GSM333717", "GSM333718", "GSM333719", "GSM333720", "GSM333721", "GSM333722", "GSM333723", "GSM333724", "GSM333725", "GSM333726", "GSM333727", "GSM333728", "GSM333729", "GSM333730", "GSM333731", "GSM333732", "GSM333733", "GSM333734", "GSM333735", "GSM333736", "GSM333737", "GSM333738", "GSM333739", "GSM333740", "GSM333741", "GSM333742", "GSM333743", "GSM333744", "GSM333745", "GSM333746", "GSM333747", "GSM333748", "GSM333749", "GSM333750", "GSM333751", "GSM333752", "GSM333753", "GSM333754", "GSM333755", "GSM333756", "GSM333757", "GSM333758", "GSM333759", "GSM333760", "GSM333761", "GSM333762", "GSM333763", "GSM333764", "GSM333765", "GSM333766", "GSM333767", "GSM333768", "GSM333769", "GSM333770", "GSM333771", "GSM333772", "GSM333773", "GSM333774", "GSM333775", "GSM333776", "GSM333777", "GSM333778", "GSM333779", "GSM333780", "GSM333781", "GSM333782", "GSM333783", "GSM333784", "GSM333785", "GSM333786", "GSM333787", "GSM333788", "GSM333789"], "sample_count": 117, "group_sizes": null, "group_sizes_basis": null, "platform": "6480", "taxon": "Homo sapiens", "title": "Relapse-related molecular signature in lung adenocarcinomas identifies patients with dismal prognosis", "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:GSE161116", "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=GSE161116", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE161116", "version": null, "note": "There were 9 LUAD and LUAD brain metastases tissues in the Gene Expression Omnibus (GEO) database GSE161116 dataset (Figure S1A). Among them, there were 10 EGFR mutant and 8 wild-type patients (Figure S1B,C). There were 11 female patients and 7 male patients (Figure S1D). The GEO GSE161116 dataset of 9 LUAD and 9 LUAD brain metastasis samples and GPL19965 annotation information were downloaded, and the expression levels of the prognostic genes were analyzed in LUAD and LUAD brain metastasis tissues by gender and EGFR mutation groups.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "There were 9 LUAD and LUAD brain metastases tissues in the Gene Expression Omnibus (GEO) database GSE161116 dataset (Figure S1A). Among them, there were 10 EGFR mutant and 8 wild-type patients (Figure S1B,C). There were 11 female patients and 7 male patients (Figure S1D). The GEO GSE161116 dataset of 9 LUAD and 9 LUAD brain metastasis samples and GPL19965 annotation information were downloaded, and the expression levels of the prognostic genes were analyzed in LUAD and LUAD brain metastasis tissues by gender and EGFR mutation groups.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM4889789", "GSM4889790", "GSM4889791", "GSM4889792", "GSM4889793", "GSM4889794", "GSM4889795", "GSM4889796", "GSM4889797", "GSM4889798", "GSM4889799", "GSM4889800", "GSM4889801", "GSM4889802", "GSM4889803", "GSM4889804", "GSM4889805", "GSM4889806", "GSM4889807", "GSM4889808", "GSM4889809", "GSM4889810", "GSM4889811", "GSM4889812", "GSM4889813", "GSM4889814", "GSM4889815", "GSM4889816"], "sample_count": 28, "group_sizes": null, "group_sizes_basis": null, "platform": "19965", "taxon": "Homo sapiens", "title": "Comparative Analysis of the Tumor Immune-Microenvironment of Primary and Brain Metastases of Non-Small-Cell Lung Cancer", "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:GSE31210", "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=GSE31210", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31210", "version": null, "note": "There were 9 LUAD and LUAD brain metastases tissues in the Gene Expression Omnibus (GEO) database GSE161116 dataset (Figure S1A). Among them, there were 10 EGFR mutant and 8 wild-type patients (Figure S1B,C). There were 11 female patients and 7 male patients (Figure S1D). The GEO GSE161116 dataset of 9 LUAD and 9 LUAD brain metastasis samples and GPL19965 annotation information were downloaded, and the expression levels of the prognostic genes were analyzed in LUAD and LUAD brain metastasis tissues by gender and EGFR mutation groups.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "There were 9 LUAD and LUAD brain metastases tissues in the Gene Expression Omnibus (GEO) database GSE161116 dataset (Figure S1A). Among them, there were 10 EGFR mutant and 8 wild-type patients (Figure S1B,C). There were 11 female patients and 7 male patients (Figure S1D). The GEO GSE161116 dataset of 9 LUAD and 9 LUAD brain metastasis samples and GPL19965 annotation information were downloaded, and the expression levels of the prognostic genes were analyzed in LUAD and LUAD brain metastasis tissues by gender and EGFR mutation groups.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM773540", "GSM773541", "GSM773542", "GSM773543", "GSM773544", "GSM773545", "GSM773546", "GSM773547", "GSM773548", "GSM773549", "GSM773550", "GSM773551", "GSM773552", "GSM773553", "GSM773554", "GSM773555", "GSM773556", "GSM773557", "GSM773558", "GSM773559", "GSM773560", "GSM773561", "GSM773562", "GSM773563", "GSM773564", "GSM773565", "GSM773566", "GSM773567", "GSM773568", "GSM773569", "GSM773570", "GSM773571", "GSM773572", "GSM773573", "GSM773574", "GSM773575", "GSM773576", "GSM773577", "GSM773578", "GSM773579", "GSM773580", "GSM773581", "GSM773582", "GSM773583", "GSM773584", "GSM773585", "GSM773586", "GSM773587", "GSM773588", "GSM773589", 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"media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7df9b657179b985e3b22e8f1138c3893bc9a6da4fe7aba3a6dcc092d3f40c537", "bytes": 2649, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#t1", "version": null, "note": "The 97 immune genes of brain metastasis were abnormally expressed in LUAD tissues", "structure": {"pmcid": "PMC8411151", "section_index": 13, "section_title": "Differentially expressed immune genes in LUAD brain metastasis", "row_count": 50, "column_count": 4}, "table": {"label": "Table 1", "caption": "The 97 immune genes of brain metastasis were abnormally expressed in LUAD tissues", "rows": [["Gene", "logFC", "Gene", "logFC"], ["IL5RA", "−1.935544008", "LTA", "1.029192307"], ["CXCL12", "−1.11625871", "C8B", "−2.503444527"], ["SERPING1", "−1.254772313", "THY1", "1.469872699"], ["ENG", "−1.481935175", "PDCD1", "1.124336529"], ["CXCR2", "−2.430598894", "TNFSF12", 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brain metastasis", "row_count": 11, "column_count": 3}, "table": {"label": "Table 2", "caption": "Hub genes of the PPI network", "rows": [["Name", "Description", "Score"], ["FOXP3", "Forkhead box P3", "6.73E+07"], ["CTLA4", "Cytotoxic T-lymphocyte associated protein 4", "6.72E+07"], ["IL6", "Interleukin 6", "6.68E+07"], ["CD19", "CD19 molecule", "6.64E+07"], ["IFNG", "Interferon gamma", "6.56E+07"], ["CD27", "CD27 molecule", "6.53E+07"], ["PRF1", "Perforin 1", "5.97E+07"], ["IL7R", "Interleukin 7 receptor", "5.34E+07"], ["TNFRSF9", "TNF receptor superfamily member 9", "5.15E+07"], ["TNFSF4", "TNF superfamily member 4", "5.12E+07"]], "row_count": 11, "column_count": 3, "numeric_cells": 20, "header_rows": 1, "locator": "section[14]/table-wrap[1]#t2"}}, {"id": "asset:table:pmid:34527340:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:03606526797e2fbbfb9625b8dc89df08bba5778ac206ecd40f0607327bd5d68c", "bytes": 2129, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#t3", "version": null, "note": "Univariate Cox regression analysis showed the influencing genes of the poor prognosis of LUAD patients", "structure": {"pmcid": "PMC8411151", "section_index": 15, "section_title": "Construction of the risk model", "row_count": 29, "column_count": 5}, "table": {"label": "Table 3", "caption": "Univariate Cox regression analysis showed the influencing genes of the poor prognosis of LUAD patients", "rows": [["Gene", "HR", "HR.95L", "HR.95H", "P value"], ["IL5RA", "0.567969541", "0.354788527", "0.909244169", "0.018460133"], ["POU2AF1", "0.845127424", "0.729284998", "0.979370705", "0.02528008"], ["TPSAB1", "0.882145437", "0.784237159", "0.992277097", "0.036696354"], ["LILRB3", "0.693103481", "0.507451451", "0.94667664", "0.021197708"], ["TNFRSF11A", "1.342513034", "1.010304964", "1.783957628", "0.042291011"], ["TNFSF12", 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"state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[2]#t4", "version": null, "note": "The multivariate Cox regression analysis and AIC screening showed that the immune genes were independent factors affecting the prognosis of LUAD patients", "structure": {"pmcid": "PMC8411151", "section_index": 15, "section_title": "Construction of the risk model", "row_count": 7, "column_count": 6}, "table": {"label": "Table 4", "caption": "The multivariate Cox regression analysis and AIC screening showed that the immune genes were independent factors affecting the prognosis of LUAD patients", "rows": [["Gene", "coef", "HR", "HR.95L", "HR.95H", "P value"], ["TNFRSF11A", "0.35878476", "1.431588634", "1.081923122", "1.894262147", "0.012037371"], ["MS4A2", "−0.333382786", "0.716495877", "0.542458352", "0.946370058", "0.018863415"], ["IL11", "0.284973997", "1.329727451", "1.038356185", "1.702859886", "0.023931533"], ["CAMP", "−0.242800806", "0.784427751", "0.613385392", "1.003165229", "0.053017128"], ["MS4A1", "−0.163327726", "0.849312801", "0.730494719", "0.98745715", "0.033660229"], ["F2RL1", "0.177638067", "1.194392953", "1.044013084", "1.366433572", "0.009672824"]], "row_count": 7, "column_count": 6, "numeric_cells": 34, "header_rows": 1, "locator": "section[15]/table-wrap[2]#t4"}}, {"id": "asset:table:pmid:34527340:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:fed65fec2a3dcd32fd01673362cbd4309af81dc1147f093558aff9da44ce03a7", "bytes": 1655, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#t5", "version": null, "note": "K-M survival analysis showed that the expression levels of the immune genes were significantly correlated with the OS and PFS in LUAD patients in the PrognoScan database", "structure": {"pmcid": "PMC8411151", "section_index": 17, "section_title": "The role of independent prognostic gene expression levels in the progression of LUAD", "row_count": 15, "column_count": 7}, "table": {"label": "Table 5", "caption": "K-M survival analysis showed that the expression levels of the immune genes were significantly correlated with the OS and PFS in LUAD patients in the PrognoScan database", "rows": [["Gene and dataset", "Prognosis", "Probe ID", "N", "P", "COX P", "HR (95% CI)"], ["TNFRSF11A-GSE31210", "OS", "207037_at", "204", "0.00634647", "0.00898712", "2.38 (1.24–4.55)"], ["TNFRSF11A-GSE31210", "OS", "238846_at", "204", "0.168781", "0.0472737", "1.65 (1.01–2.72)"], ["TNFRSF11A-GSE31210", "RFS", "238846_at", "204", "0.0270956", "0.0154956", "1.60 (1.09–2.34)"], ["TNFRSF11A-GSE31210", "RFS", "207037_at", "204", "0.0180054", "0.0221418", "1.84 (1.09–3.10)"], ["MS4A2-GSE31210", "OS", "207496_at", "204", "0.00987325", "0.00296026", "0.54 (0.36–0.81)"], ["MS4A2-GSE31210", "OS", "207497_s_at", "204", "0.0173826", "0.0307801", "0.58 (0.35–0.95)"], ["MS4A2-Jacob-00182-UM", "OS", "207496_at", "178", "0.086174", "0.0336075", "0.79 (0.63–0.98)"], ["MS4A2-GSE31210", "RFS", "207496_at", "204", "0.00155053", "0.0032846", "0.64 (0.48–0.86)"], ["MS4A1-Jacob-00182-UM", "OS", "210356_x_at", "178", "0.259787", "0.0342218", "0.69 (0.49–0.97)"], ["MS4A1-Jacob-00182-UM", "OS", "217418_x_at", "178", "0.168491", "0.0421624", "0.76 (0.59–0.99)"], ["IL11-Jacob-00182-CANDF", "OS", "206924_at", "82", "–", "0.0146906", "1.96 (1.14–3.36)"], ["IL11-GSE31210", "OS", "206924_at", "204", "0.046182", "0.248705", "1.28 (0.84–1.95)"], ["F2RL1-GSE13213", "OS", "A_23_P58835", "117", "0.0159142", "0.0256215", "1.29 (1.03–1.61)"], ["CAMP-MICHIGAN-LC", "OS", "Z38026_at", "86", "0.00882622", "0.207221", "0.61 (0.28–1.32)"]], "row_count": 15, "column_count": 7, "numeric_cells": 83, "header_rows": 1, "locator": "section[17]/table-wrap[1]#t5"}}, {"id": "asset:table:pmid:34527340:6", "role": "table", "format": "jats-table", "media_type": 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"asset:data:geo:GSE161116 not downloaded", "asset:data:geo:GSE161116 licence not read", "asset:data:geo:GSE31210 not downloaded", "asset:data:geo:GSE31210 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-2", "family": "differential_expression", "specific": "limma_voom", "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": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-3", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}, {"id": "method-4", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC analysis"}}, {"id": "method-5", "family": null, "specific": null, "label": "K-M survival analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "K-M survival analysis of the GSE31210 and Jacob-00182-UM datasets showed that the expression levels of TNFRSF11A and MS4A2 were significantly correlated with the OS and relapse free survival (RFS) in LUAD patients."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE161116", "GSE31210", "GSE13213"], "resolved_accessions": ["GSE161116", "GSE31210", "GSE13213"], "statements": ["There were 9 LUAD and LUAD brain metastases tissues in the Gene Expression Omnibus (GEO) database GSE161116 dataset (Figure S1A). Among them, there were 10 EGFR mutant and 8 wild-type patients (Figure S1B,C). There were 11 female patients and 7 male patients (Figure S1D). The GEO GSE161116 dataset of 9 LUAD and 9 LUAD brain metastasis samples and GPL19965 annotation information were downloaded, and the expression levels of the prognostic genes were analyzed in LUAD and LUAD brain metastasis tissues by gender and EGFR mutation groups."], "basis": "The paper names GSE161116, GSE31210, GSE13213 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:34527340", "data:geo:GSE13213", "asset:table:pmid:34527340:1", "asset:table:pmid:34527340:2", "asset:table:pmid:34527340:3", "asset:table:pmid:34527340:4", "asset:table:pmid:34527340:5", "asset:table:pmid:34527340:6"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE13213"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:50Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 30946, "completion_tokens": 2916, "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:34527340", "type": "paper", "label": "pmid:34527340"}, {"id": "source:pmid:34527340", "type": "manuscript", "label": "PMID 34527340 full text"}, {"id": "data:geo:GSE13213", "type": "dataset", "label": "GEO GSE13213"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34527340", "type": "paper", "label": "pmid:34527340"}, {"id": "source:pmid:34527340", "type": "manuscript", "label": "PMID 34527340 full text"}, {"id": "data:geo:GSE13213", "type": "dataset", "label": "GEO GSE13213"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34527340", "type": "extraction", "used": ["source:pmid:34527340"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE13213", "type": "accession_resolution", "used": ["data:geo:GSE13213"], "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:34527340", "parent_hash": "sha256:f663ebda65fd666cce3c0846665aace0ece2e9681eecab67951d009fe74067df", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE13213 licence not read", "asset:data:geo:GSE13213 not downloaded", "asset:data:geo:GSE161116 licence not read", "asset:data:geo:GSE161116 not downloaded", "asset:data:geo:GSE31210 licence not read", "asset:data:geo:GSE31210 not downloaded", "execution.not_run", "method.reader_named_unmapped", "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": 0.7, "evidence": ["Cox regression"], "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":"2026-11-04T01:32:17+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}}}