Identification and Validation of a Tumor Microenvironment-Related Gene Signature for Prognostic Prediction in Advanced-Stage Non-Small-Cell Lung Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33860055", "kind": "science-record", "revision": 7, "content_hash": "sha256:0ca7a5f3e142122be2ef624153301494df27d6d9c0ab06b0b5a602c799ef3f02", "created_at": "2026-11-01T15:41:32Z", "updated_at": "2026-11-01T22:03:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of a Tumor Microenvironment-Related Gene Signature for Prognostic Prediction in Advanced-Stage Non-Small-Cell Lung Cancer.", "doi": "10.1155/2021/8864436", "pmid": "33860055", "authors": ["Xuening Zhang", "Xuezhong Shi", "Hao Zhao", "Xiaocan Jia", "Yongli Yang"], "journal": "BioMed research international", "year": 2021, "abstract": "The development of immunotherapy has greatly changed the advanced-stage non-small-cell lung cancer (NSCLC) treatment landscape. The complexity and heterogeneity of tumor microenvironment (TME) lead to discrepant immunotherapy effects among patients at the same pathologic stages. This study is aimed at exploring potential biomarkers of immunotherapy and accurately predicting the prognosis for advanced NSCLC patients. RNA-seq data and clinical information on stage III/IV NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). In TCGA-NSCLC with stage III/IV (n = 192), immune scores and stromal scores were calculated by using the ESTIMATE algorithms. Univariate, LASSO, and multivariate Cox regression analyses were performed to screen prognostic TME-related genes (TMERGs) and constructed a gene signature risk score model. It was validated in external dataset including GSE41271 (n = 91) and GSE81089 (n = 36). Additionally, a nomogram incorporating TMERG signature risk score and clinical characteristics was established. Further, we accessed the proportion of 22 types of tumor-infiltrating immune cells (TIIC) from the CIBERSORT website and analyzed the difference between two risk groups. OS of patients with high immune/stromal scores were higher (log-rank P = 0.044/log-rank P = 0.048). Multivariate Cox regression identified six prognostic TMERGs, including CD200, CHI3L2, CNTN1, CTSL, FYB1, and SLC52A1. We developed a six-gene risk score model, which was validated as an independent prognostic factor for OS (HR: 3.32, 95% CI: 2.16-5.09). Time-ROC curves showed useful discrimination for TCGA-NSCLC cohort (1-, 2-, and 3-year AUCs were 0.718, 0.761, and 0.750). The predictive robustness was validated in the external dataset. The C-index and 1-, 2-, and 3-year AUCs of nomogram were the largest, which demonstrated the nomogram had the greatest predictive accuracy and effectiveness and could be used for clinical guidance. Besides, the increased infiltration of T cells regulatory (Tregs) and macrophages M2 in the high-risk group suggested that chronic inflammation may reduce survival probability in patients with advanced NSCLC. We conducted a comprehensive analysis of the tumor microenvironment and identified the TMERG signature, which could predict prognosis accurately and provide a reference for the personalized immunotherapy for advanced NSCLC patients.", "claims": [{"id": "claim-method", "statement": "Univariate, LASSO, and multivariate Cox regression analyses were performed to screen prognostic TME-related genes (TMERGs) and constructed a gene signature risk score model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33860055", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Univariate, LASSO, and multivariate Cox regression analyses were performed to screen prognostic TME-related genes (TMERGs) and constructed a gene signature risk score model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) is used to provide RNA-seq data and the clinical data of NSCLC in training set . The Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) is used to provide RNA-seq data in validation set.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33860055", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) is used to provide RNA-seq data and the clinical data of NSCLC in training set . The Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) is used to provide RNA-seq data in validation set."}], "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:33860055"], "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:GSE41271"], "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:GSE41271"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33860055", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/8864436", "sha256": "sha256:f74519abf7dd625f2610aa9ace559bccab96c79f3cd10a93ae32f65cef380238", "bytes": 56136, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/8864436", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8028741", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE41271", "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=GSE41271", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE41271", "version": null, "note": "The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) is used to provide RNA-seq data and the clinical data of NSCLC in training set . The Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) is used to provide RNA-seq data in validation set.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) is used to provide RNA-seq data and the clinical data of NSCLC in training set . The Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) is used to provide RNA-seq data in validation set.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1012828", "GSM1012829", "GSM1012830", "GSM1012831", "GSM1012832", "GSM1012833", "GSM1012834", "GSM1012835", "GSM1012836", "GSM1012837", "GSM1012838", "GSM1012839", "GSM1012840", "GSM1012841", "GSM1012842", "GSM1012843", "GSM1012844", "GSM1012845", "GSM1012846", "GSM1012847", "GSM1012848", "GSM1012849", "GSM1012850", "GSM1012851", "GSM1012852", "GSM1012853", "GSM1012854", "GSM1012855", "GSM1012856", "GSM1012857", "GSM1012858", "GSM1012859", "GSM1012860", "GSM1012861", "GSM1012862", "GSM1012863", "GSM1012864", "GSM1012865", "GSM1012866", "GSM1012867", "GSM1012868", "GSM1012869", "GSM1012870", "GSM1012871", "GSM1012872", "GSM1012873", "GSM1012874", "GSM1012875", "GSM1012876", "GSM1012877", "GSM1012878", "GSM1012879", "GSM1012880", "GSM1012881", "GSM1012882", "GSM1012883", "GSM1012884", "GSM1012885", "GSM1012886", "GSM1012887", "GSM1012888", "GSM1012889", "GSM1012890", "GSM1012891", "GSM1012892", "GSM1012893", "GSM1012894", "GSM1012895", "GSM1012896", "GSM1012897", "GSM1012898", "GSM1012899", "GSM1012900", "GSM1012901", "GSM1012902", "GSM1012903", "GSM1012904", "GSM1012905", "GSM1012906", "GSM1012907", "GSM1012908", "GSM1012909", "GSM1012910", "GSM1012911", "GSM1012912", "GSM1012913", "GSM1012914", "GSM1012915", "GSM1012916", "GSM1012917", "GSM1012918", "GSM1012919", "GSM1012920", "GSM1012921", "GSM1012922", "GSM1012923", "GSM1012924", "GSM1012925", "GSM1012926", "GSM1012927", "GSM1012928", "GSM1012929", "GSM1012930", "GSM1012931", "GSM1012932", "GSM1012933", "GSM1012934", "GSM1012935", "GSM1012936", "GSM1012937", "GSM1012938", "GSM1012939", "GSM1012940", "GSM1012941", "GSM1012942", "GSM1012943", "GSM1012944", "GSM1012945", "GSM1012946", "GSM1012947", "GSM1012948", "GSM1012949", "GSM1012950", "GSM1012951", "GSM1012952", "GSM1012953", "GSM1012954", "GSM1012955", "GSM1012956", "GSM1012957", "GSM1012958", "GSM1012959", "GSM1012960", "GSM1012961", "GSM1012962", "GSM1012963", "GSM1012964", "GSM1012965", "GSM1012966", "GSM1012967", "GSM1012968", "GSM1012969", "GSM1012970", "GSM1012971", "GSM1012972", "GSM1012973", "GSM1012974", "GSM1012975", "GSM1012976", "GSM1012977", "GSM1012978", "GSM1012979", "GSM1012980", "GSM1012981", "GSM1012982", "GSM1012983", "GSM1012984", "GSM1012985", "GSM1012986", "GSM1012987", "GSM1012988", "GSM1012989", "GSM1012990", "GSM1012991", "GSM1012992", "GSM1012993", "GSM1012994", "GSM1012995", "GSM1012996", "GSM1012997", "GSM1012998", "GSM1012999", "GSM1013000", "GSM1013001", "GSM1013002", "GSM1013003", "GSM1013004", "GSM1013005", "GSM1013006", "GSM1013007", "GSM1013008", "GSM1013009", "GSM1013010", "GSM1013011", "GSM1013012", "GSM1013013", "GSM1013014", "GSM1013015", "GSM1013016", "GSM1013017", "GSM1013018", "GSM1013019", "GSM1013020", "GSM1013021", "GSM1013022", "GSM1013023", "GSM1013024", "GSM1013025", "GSM1013026", "GSM1013027", "GSM1013028", "GSM1013029", "GSM1013030", "GSM1013031", "GSM1013032", "GSM1013033", "GSM1013034", "GSM1013035", "GSM1013036", "GSM1013037", "GSM1013038", "GSM1013039", "GSM1013040", "GSM1013041", "GSM1013042", "GSM1013043", "GSM1013044", "GSM1013045", "GSM1013046", "GSM1013047", "GSM1013048", "GSM1013049", "GSM1013050", "GSM1013051", "GSM1013052", "GSM1013053", "GSM1013054", "GSM1013055", "GSM1013056", "GSM1013057", "GSM1013058", "GSM1013059", "GSM1013060", "GSM1013061", "GSM1013062", "GSM1013063", "GSM1013064", "GSM1013065", "GSM1013066", "GSM1013067", "GSM1013068", "GSM1013069", "GSM1013070", "GSM1013071", "GSM1013072", "GSM1013073", "GSM1013074", "GSM1013075", "GSM1013076", "GSM1013077", "GSM1013078", "GSM1013079", "GSM1013080", "GSM1013081", "GSM1013082", "GSM1013083", "GSM1013084", "GSM1013085", "GSM1013086", "GSM1013087", "GSM1013088", "GSM1013089", "GSM1013090", "GSM1013091", "GSM1013092", "GSM1013093", "GSM1013094", "GSM1013095", "GSM1013096", "GSM1013097", "GSM1013098", "GSM1013099", "GSM1013100", "GSM1013101", "GSM1013102"], "sample_count": 275, "group_sizes": null, "group_sizes_basis": null, "platform": "6884", "taxon": "Homo sapiens", "title": "Expression profiling of 275 lung cancer specimens", "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:GSE81089", "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=GSE81089", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE81089", "version": null, "note": "The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) is used to provide RNA-seq data and the clinical data of NSCLC in training set . The Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) is used to provide RNA-seq data in validation set.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) is used to provide RNA-seq data and the clinical data of NSCLC in training set . The Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) is used to provide RNA-seq data in validation set.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2142443", "GSM2142444", "GSM2142445", "GSM2142446", "GSM2142447", "GSM2142448", "GSM2142449", "GSM2142450", "GSM2142451", "GSM2142452", "GSM2142453", "GSM2142454", "GSM2142455", "GSM2142456", "GSM2142457", "GSM2142458", "GSM2142459", "GSM2142460", "GSM2142461", "GSM2142462", "GSM2142463", "GSM2142464", "GSM2142465", "GSM2142466", "GSM2142467", "GSM2142468", "GSM2142469", "GSM2142470", "GSM2142471", "GSM2142472", "GSM2142473", "GSM2142474", "GSM2142475", "GSM2142476", "GSM2142477", "GSM2142478", "GSM2142479", "GSM2142480", "GSM2142481", "GSM2142482", "GSM2142483", "GSM2142484", "GSM2142485", "GSM2142486", "GSM2142487", "GSM2142488", "GSM2142489", "GSM2142490", "GSM2142491", "GSM2142492", "GSM2142493", "GSM2142494", "GSM2142495", "GSM2142496", "GSM2142497", "GSM2142498", "GSM2142499", "GSM2142500", "GSM2142501", "GSM2142502", "GSM2142503", "GSM2142504", "GSM2142505", "GSM2142506", "GSM2142507", "GSM2142508", "GSM2142509", "GSM2142510", "GSM2142511", "GSM2142512", "GSM2142513", "GSM2142514", "GSM2142515", "GSM2142516", "GSM2142517", "GSM2142518", "GSM2142519", "GSM2142520", "GSM2142521", "GSM2142522", "GSM2142523", "GSM2142524", "GSM2142525", "GSM2142526", "GSM2142527", "GSM2142528", "GSM2142529", "GSM2142530", "GSM2142531", "GSM2142532", "GSM2142533", "GSM2142534", "GSM2142535", "GSM2142536", "GSM2142537", "GSM2142538", "GSM2142539", "GSM2142540", "GSM2142541", "GSM2142542", "GSM2142543", "GSM2142544", "GSM2142545", "GSM2142546", "GSM2142547", "GSM2142548", "GSM2142549", "GSM2142550", "GSM2142551", "GSM2142552", "GSM2142553", "GSM2142554", "GSM2142555", "GSM2142556", "GSM2142557", "GSM2142558", "GSM2142559", "GSM2142560", "GSM2142561", "GSM2142562", "GSM2142563", "GSM2142564", "GSM2142565", "GSM2142566", "GSM2142567", "GSM2142568", "GSM2142569", "GSM2142570", "GSM2142571", "GSM2142572", "GSM2142573", "GSM2142574", "GSM2142575", "GSM2142576", "GSM2142577", "GSM2142578", "GSM2142579", "GSM2142580", "GSM2142581", "GSM2142582", "GSM2142583", "GSM2142584", "GSM2142585", "GSM2142586", "GSM2142587", "GSM2142588", "GSM2142589", "GSM2142590", "GSM2142591", "GSM2142592", "GSM2142593", "GSM2142594", "GSM2142595", "GSM2142596", "GSM2142597", "GSM2142598", "GSM2142599", "GSM2142600", "GSM2142601", "GSM2142602", "GSM2142603", "GSM2142604", "GSM2142605", "GSM2142606", "GSM2142607", "GSM2142608", "GSM2142609", "GSM2142610", "GSM2142611", "GSM2142612", "GSM2142613", "GSM2142614", "GSM2142615", "GSM2142616", "GSM2142617", "GSM2142618", "GSM2142619", "GSM2142620", "GSM2142621", "GSM2142622", "GSM2142623", "GSM2142624", "GSM2142625", "GSM2142626", "GSM2142627", "GSM2142628", "GSM2142629", "GSM2142630", "GSM2142631", "GSM2142632", "GSM2142633", "GSM2142634", "GSM2142635", "GSM2142636", "GSM2142637", "GSM2142638", "GSM2142639", "GSM2142640", "GSM2142641", "GSM2142642", "GSM2142643", "GSM2142644", "GSM2142645", "GSM2142646", "GSM2142647", "GSM2142648", "GSM2142649", "GSM2142650", "GSM2142651", "GSM2142652", "GSM2142653", "GSM2142654", "GSM2142655", "GSM2142656", "GSM2142657", "GSM2142658", "GSM2142659", "GSM2142660"], "sample_count": 218, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "Next Generation Sequencing (RNAseq) of non-small cell lung cancer", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33860055:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a5c32fb3020ad1a5569bd626429238e31325faff8d2feb33dc1a9bdbb73caef2", "bytes": 1378, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#tab1", "version": null, "note": "The clinical characteristics of advanced NSCLC in training and validation cohort (n (%)).", "structure": {"pmcid": "PMC8028741", "section_index": 11, "section_title": "3.1. Patient Demographic and Clinical Characteristic", "row_count": 30, "column_count": 4}, "table": {"label": "Table 1", "caption": "The clinical characteristics of advanced NSCLC in training and validation cohort (n (%)).", "rows": [["Characteristics", "Training set", "Validation set"], ["TCGA (n = 192)", "GSE41271 (n = 91)", "GSE81089 (n = 36)"], ["Age (year)", "", "", ""], ["<65", "82 (42.71)", "33 (36.26)", "13 (36.11)"], ["≥65", "110 (57.29)", "58 (63.74)", "23 (63.89)"], ["Gender", "", "", ""], ["Male", "117 (60.94)", "54 (59.34)", "14 (38.89)"], ["Female", "75 (39.06)", "37 (40.66)", "22 (61.11)"], ["Histological type", "", "", ""], ["LUAD", "104 (54.17)", "55 (60.44)", "27 (75)"], ["LUSC", "88 (45.83)", "36 (39.56)", "9 (25)"], ["Metastasis (M_stage)", "", "", ""], ["M0", "160 (83.33)", "85 (93.41)", "33 (91.67)"], ["M1", "32 (16.67)", "6 (6.59)", "3 (8.33)"], ["Lymph node (N_stage)", "", "", ""], ["N0", "30 (15.63)", "—", "—"], ["N1", "47 (24.48)", "—", "—"], ["N2", "106 (55.21)", "—", "—"], ["N3", "9 (4.69)", "—", "—"], ["Tumor invasion (T_stage)", "", "", ""], ["T1", "21 (10.94)", "—", "—"], ["T2", "85 (44.27)", "—", "—"], ["T3", "45 (23.44)", "—", "—"], ["T4", "41 (21.35)", "—", "—"], ["Tumor stage", "", "", ""], ["III", "160 (83.33)", "85 (93.41)", "33 (91.67)"], ["IV", "32 (16.67)", "6 (6.59)", "3 (8.33)"], ["Smoking", "", "", ""], ["Yes", "166 (86.46)", "80 (87.91)", "—"], ["No", "26 (13.54)", "11 (12.09)", "—"]], "row_count": 30, "column_count": 4, "numeric_cells": 47, "header_rows": 2, "locator": "section[11]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:33860055:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c403068f69f1f5c1bc84dc74e989e84c833d975fe1091ecd38fb6a607223912e", "bytes": 743, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#tab2", "version": null, "note": "Comparison of the nomogram with the N stage, T stage, and risk score model.", "structure": {"pmcid": "PMC8028741", "section_index": 16, "section_title": "3.6. Construction of Nomogram and Performance Assessment", "row_count": 5, "column_count": 5}, "table": {"label": "Table 2", "caption": "Comparison of the nomogram with the N stage, T stage, and risk score model.", "rows": [["Models", "1-year AUC (95% CI)", "2-year AUC (95% CI)", "3-year AUC (95% CI)", "C-index (95% CI)"], ["N stage model", "0.560 (0.465-0.655)", "0.612 (0.532-0.693)", "0.566 (0.475-0.657)", "0.558 (0.499-0.617)"], ["T stage model", "0.576 (0.482-0.669)", "0.587 (0.499-0.675)", "0.595 (0.496-0.694)", "0.569 (0.510-0.628)"], ["Risk score model", "0.718 (0.641-0.796)", "0.761 (0.695-0.827)", "0.750 (0.681-0.818)", "0.639 (0.586-0.692)"], ["Nomogram", "0.720 (0.629-0.812)", "0.799 (0.726-0.872)", "0.772 (0.693-0.851)", "0.703 (0.650-0.756)"]], "row_count": 5, "column_count": 5, "numeric_cells": 20, "header_rows": 1, "locator": "section[16]/table-wrap[1]#tab2"}}], "gaps": ["asset:data:geo:GSE41271 not downloaded", "asset:data:geo:GSE41271 licence not read", "asset:data:geo:GSE81089 not downloaded", "asset:data:geo:GSE81089 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": 1.0, "band": "verbatim", "quote": "Univariate, LASSO, and multivariate Cox regression analyses were performed to screen prognostic TME-related genes (TMERGs) and constructed a gene signature risk score model."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-3", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-4", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "log-rank"}}, {"id": "method-5", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman's correlation"}}, {"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"}}], "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": ["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": ["GSE41271", "GSE81089"], "resolved_accessions": ["GSE41271", "GSE81089"], "statements": ["The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) is used to provide RNA-seq data and the clinical data of NSCLC in training set . The Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) is used to provide RNA-seq data in validation set."], "basis": "The paper names GSE41271, GSE81089 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:33860055", "data:geo:GSE41271", "asset:table:pmid:33860055:1", "asset:table:pmid:33860055:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE41271"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:29:10Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 43193, "completion_tokens": 2222, "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:33860055", "type": "paper", "label": "pmid:33860055"}, {"id": "source:pmid:33860055", "type": "manuscript", "label": "PMID 33860055 full text"}, {"id": "data:geo:GSE41271", "type": "dataset", "label": "GEO GSE41271"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33860055", "type": "paper", "label": "pmid:33860055"}, {"id": "source:pmid:33860055", "type": "manuscript", "label": "PMID 33860055 full text"}, {"id": "data:geo:GSE41271", "type": "dataset", "label": "GEO GSE41271"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33860055", "type": "extraction", "used": ["source:pmid:33860055"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE41271", "type": "accession_resolution", "used": ["data:geo:GSE41271"], "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:33860055", "parent_hash": "sha256:a43f20a4cfe4ff6be94cf5ff5524cd4852c22b741d9559d211fc074e4dba6556", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE41271 licence not read", "asset:data:geo:GSE41271 not downloaded", "asset:data:geo:GSE81089 licence not read", "asset:data:geo:GSE81089 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": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["g the prognosis for advanced NSCLC patients. RNA-seq data and clinical information on stage III/I"], "order_basis": "paper_text_order:528", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Univariate, LASSO, and multivariate Cox regression analyses were performed to screen prognostic TME-related genes (TMERGs) and constructed a gene signature risk score model."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}