{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33411689", "kind": "science-record", "revision": 8, "content_hash": "sha256:ef3e2e6922db7b64dc5b52ee2128eb9e63454d27866c1f05b23a16a5acd2662d", "created_at": "2026-11-01T15:41:21Z", "updated_at": "2026-11-01T22:02:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "High expression of RRM2 as an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.", "doi": "10.18632/aging.202292", "pmid": "33411689", "authors": ["Cheng-Yu Jin", "Liang Du", "A-Han Nuerlan", "Xiao-Lei Wang", "Yong-Wei Yang", "Rui Guo"], "journal": "Aging", "year": 2020, "abstract": "Ribonucleotide reductase subunit M2 may play a role as a potential prognostic biomarker in several cancers. In this study, we evaluated whether RRM2 gene expression is associated with the prognosis of patients with lung adenocarcinoma (LUAD) using publicly available data from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and logistic regression were performed to evaluate the association between RRM2 expression and clinical features in patients with LUAD. Kaplan-Meier and Cox regression methods were used to examine the effect of RRM2 expression level in the overall survival, and a nomogram was performed to illustrate the correlation between the RRM2 gene expression and the risk of LUAD. TCGA data set was used for gene set enrichment analysis (GSEA). We also performed a further experiment in vitro to assess the effect of RRM2 expression on the proliferation and invasive abilities of LUAD cells and its key signaling pathway proteins. Our results revealed that the expression level of RRM2 in patients with LUAD was much higher than that in normal tissues (p = 3.99e-32). High expression of RRM2 was significantly associated with tumor stage (IV vs. I: OR = 3.02, p = 0.012) and TNM classification (T2 vs. T1: OR = 1.88, p = 0.001; N2 vs. N0: OR = 2.69, p < 0.001). Kaplan-Meier survival analysis showed that high expression of RRM2 was associated with a worse prognosis of LUAD compared low expression of RRM2 (p = 7.86e-04). Multivariate analysis showed that high RRM2 expression was an independent factor affecting overall survival (HR = 1.29, p < 0.001). The association between RRM2 gene expression and the risk of LUAD was presented in a nomogram. GSEA revealed that the cell cycle, p53 signaling pathway, DNA replication, small cell lung cancer, apoptosis, and pathways in cancer were differentially enriched in patients with high expression of RRM2. RRM2 over-expression promoted the proliferation and invasive abilities of LUAD cells. RRM2 over-expression increased the activation of Bcl-2 and E-cadherin signaling pathways, and reduced the activation of p53 signaling pathway. In summary, high RRM2 expression is an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier survival analysis showed that high RRM2 expression was associated with poor prognosis (p = 7.86e-04), as shown in Figure 3A.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33411689", "locator": "sections[6] \"High expression of RRM2 is an independent risk factor for overall survival\" paragraph 2", "quote": "Kaplan-Meier survival analysis showed that high RRM2 expression was associated with poor prognosis (p = 7.86e-04), as shown in Figure 3A."}], "state": "complete"}, {"id": "claim-data-access", "statement": "mRNA expression data (535 samples, Workflow Type: HTSeq-FPKM) and clinical information were downloaded from TCGA database (https://cancergenome.nih.gov). The following samples were excluded: (1) “0” gene expression value and (2) insufficient survival information. A total of 503 patients with LUAD with the corresponding clinical features were enrolled in this study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33411689", "locator": "sections[14] \"Patient data sets\" paragraph 2", "quote": "mRNA expression data (535 samples, Workflow Type: HTSeq-FPKM) and clinical information were downloaded from TCGA database (https://cancergenome.nih.gov). The following samples were excluded: (1) “0” gene expression value and (2) insufficient survival information. A total of 503 patients with LUAD with the corresponding clinical features were enrolled in this study."}], "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:33411689"], "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:GSE30219"], "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:GSE30219"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33411689", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.202292", "sha256": "sha256:74da61ea0b922429e34465e6e92865b72a5d5fa4b2e4d6c96da8adb6bcff4677", "bytes": 32517, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.18632/aging.202292", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7906179", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE30219", "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=GSE30219", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE30219", "version": null, "note": "mRNA expression data (535 samples, Workflow Type: HTSeq-FPKM) and clinical information were downloaded from TCGA database (https://cancergenome.nih.gov). The following samples were excluded: (1) “0” gene expression value and (2) insufficient survival information. A total of 503 patients with LUAD with the corresponding clinical features were enrolled in this study.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "mRNA expression data (535 samples, Workflow Type: HTSeq-FPKM) and clinical information were downloaded from TCGA database (https://cancergenome.nih.gov). The following samples were excluded: (1) “0” gene expression value and (2) insufficient survival information. 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">=65", "280", "55.7"], ["Gender", "Female", "270", "53.7"], ["", "Male", "233", "46.3"], ["Race", "Asian", "9", "2.0"], ["", "non-Asian", "446", "98.0"], ["Stage", "I", "268", "54.1"], ["", "II", "120", "24.2"], ["", "III", "81", "16.4"], ["", "IV", "26", "5.3"], ["Smoking status", "Current smoker", "118", "24.1"], ["", "Ever smoker", "301", "61.2"], ["", "Never smoker", "70", "14.7"], ["T classification", "T1", "171", "33.2"], ["", "T2", "265", "53.0"], ["", "T3", "45", "9.0"], ["", "T4", "19", "3.8"], ["M classification", "M0", "334", "93.0"], ["", "M1", "25", "7.0"], ["N classification", "N0", "323", "66.1"], ["", "N1", "95", "19.4"], ["", "N2", "71", "14.5"], ["Location in lung", "Central", "64", "36.8"], ["", "Peripheral", "110", "63.2"], ["Radiation therapy", "Yes", "13", "8.3"], ["", "No", "144", "91.7"], ["New tumor event after initial treatment", "Yes", "31", "16.6"], ["", "No", "156", "83.4"], ["EGFR mutation", "Yes", "80", "29.4"], ["", "No", "192", "70.6"], ["KRAS 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"section_title": "Correlation between RRM2 expression and clinical features", "row_count": 28, "column_count": 7}, "table": {"label": "Table 2", "caption": "Logistic analysis of the association between RRM2 expression and clinical characteristics.", "rows": [["Clinical characteristics", "Total (N)", "RRM2 expression"], ["", "OR", "95%CI", "", "p-Value"], ["Age (>=65 vs. <65)", "503", "", "0.72", "0.50-1.03", "", "0.071"], ["Gender (Male vs. Female)", "503", "", "1.36", "0.96-1.93", "", "0.085"], ["Race (non-Asian vs. Asian)", "455", "", "0.99", "0.23-4.26", "", "0.995"], ["Stage", "495", "", "", "", "", ""], ["I", "", "", "Reference", "", ""], ["II", "", "", "1.56", "1.01-2.40", "", "0.043"], ["III", "", "", "2.18", "1.33-3.63", "", "0.002"], ["IV", "", "", "3.02", "1.31-7.58", "", "0.012"], ["Smoking status", "489", "", "", "", "", ""], ["Current smoker", "", "", "Reference", "", ""], ["Ever smoker", "", "", "0.40", "0.25-0.62", "", "4.66e-05"], ["Never smoker", "", "", "0.33", "0.18-0.60", "", "<0.001"], ["T (T2 vs. T1)", "436", "", "1.88", "1.28-2.79", "", "0.001"], ["M (M1 vs. M0)", "359", "", "2.25", "0.97-5.65", "", "0.066"], ["N classification", "489", "", "", "", "", ""], ["N0", "", "", "Reference", "", "", ""], ["N1", "", "", "1.78", "1.12-2.83", "", "0.015"], ["N2", "", "", "2.69", "1.59-4.65", "", "<0.001"], ["Location (central vs. peripheral)", "174", "", "1.60", "0.87-2.97", "", "0.135"], ["Radiation therapy (yes vs. no)", "157", "", "2.42", "0.75-9.25", "", "0.158"], ["New tumor event after initial treatment (yes vs. no)", "187", "", "2.28", "1.02-5.37", "", "0.049"], ["EGFR mutation (yes vs. no)", "272", "", "0.76", "0.45-1.28", "", "0.306"], ["KRAS mutation (yes vs. no)", "62", "", "0.50", "0.17-1.40", "", "0.191"], ["EML4-ALK translocation (yes vs. no)", "242", "", "1.16", "0.56-2.41", "", "0.692"], ["Person neoplasm cancer status (with tumor vs tumor free)", "407", "", "1.73", "1.12-2.71", "", "0.014"], ["Primary therapy outcomes (SD+PD vs. CR+PR)", "151", "", "1.44", "0.55-3.94", "", "0.463"]], "row_count": 28, "column_count": 7, "numeric_cells": 78, "header_rows": 0, "locator": "section[5]/table-wrap[1]#t2"}}, {"id": "asset:table:pmid:33411689:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d394e4f932667dc64ecf5125f74155d54f0cfc17f0e4074dbf284d5c6064269d", "bytes": 1534, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[6]/table-wrap[1]#t3", "version": null, "note": "Univariate and multivariate Cox regression analyses of clinical characteristics associated with overall survival.", "structure": {"pmcid": "PMC7906179", "section_index": 6, "section_title": "High expression of RRM2 is an independent risk factor for overall survival", "row_count": 19, "column_count": 8}, "table": {"label": "Table 3", "caption": "Univariate and multivariate Cox regression analyses of clinical characteristics associated with overall survival.", "rows": [["Clinical characteristics", "Univariate analysis", "", "Multivariate analysis"], ["HR", "95%CI", "p-Value", "", "HR", "95%CI", "p-Value"], ["Age", "1.18", "0.86-1.63", "0.309", "", "1.36", "0.96-1.93", "0.083"], ["Gender", "1.04", "0.76-1.43", "0.789", "", "1.13", "0.80-1.59", "0.487"], ["Race", "2.01", "0.28-14.35", "0.488", "", "", "", ""], ["Stage", "1.67", "1.44-1.93", "1.12e-11", "", "1.28", "1.01-1.64", "0.043"], ["Smoking status", "0.92", "0.72-1.19", "0.540", "", "0.84", "0.65-1.10", "0.207"], ["T", "1.53", "1.25-1.86", "3.12e-05", "", "1.16", "0.90-1.51", "0.245"], ["M", "0.92", "0.77-1.11", "0.386", "", "1.13", "0.91-1.39", "0.259"], ["N", "1.72", "1.44-2.06", "1.82e-09", "", "1.39", "1.05-1.84", "0.022"], ["Location", "0.95", "0.57-1.58", "0.829", "", "", "", ""], ["Radiation therapy", "2.87", "1.32-6.23", "0.007", "", "", "", ""], ["New tumor event after initial treatment", "2.3", "1.31-4.05", "0.003", "", "", "", ""], ["EGFR mutation", "1.33", "0.82-2.15", "0.242", "", "", "", ""], ["KRAS mutation", "2.21", "0.85-5.76", "0.103", "", "", "", ""], ["EML4-ALK translocation", "1.96", "1.06-3.63", "0.031", "", "", "", ""], ["Primary therapy outcomes", "2.44", "0.90-6.59", "0.078", "", "", "", ""], ["Person neoplasm cancer status", "4.74", "3.27-6.87", "2.08e-16", "", "1.69", "1.37-2.08", "7.20e-07"], ["RRM2 expression", "1.34", "1.16-1.54", "4.86e-05", "", "1.29", "1.11-1.50", "<0.001"]], "row_count": 19, "column_count": 8, "numeric_cells": 80, "header_rows": 0, "locator": "section[6]/table-wrap[1]#t3"}}, {"id": "asset:table:pmid:33411689:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:34cfb899324ed01925e00e64c6697aa318ff7780ad9454676ea0af805aea9a6b", "bytes": 650, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#t4", "version": null, "note": "Gene sets enriched in the high RRM2 expression phenotype.", "structure": {"pmcid": "PMC7906179", "section_index": 8, "section_title": "GSEA identifies a RRM2-related signaling pathway", "row_count": 7, "column_count": 6}, "table": {"label": "Table 4", "caption": "Gene sets enriched in the high RRM2 expression phenotype.", "rows": [["Gene set name", "SIZE", "ES", "NES", "NOM p-Val", "FDR q-Val"], ["KEGG_CELL_CYCLE", "124", "0.839", "2.697", "<0.001", "<0.001"], ["KEGG_P53_SIGNALING_PATHWAY", "66", "0.666", "2.49", "<0.001", "<0.001"], ["KEGG_DNA_REPLICATION", "36", "0.942", "2.242", "<0.001", "1.56e-04"], ["KEGG_SMALL_CELL_LUNG_CANCER", "84", "0.553", "2.077", "<0.001", "0.003"], ["KEGG_APOPTOSIS", "86", "0.454", "1.758", "0.013", "0.032"], ["KEGG_PATHWAYS_IN_CANCER", "324", "0.44", "1.863", "0.004", "0.018"]], "row_count": 7, "column_count": 6, "numeric_cells": 31, "header_rows": 0, "locator": "section[8]/table-wrap[1]#t4"}}], "gaps": ["asset:data:geo:GSE30219 not downloaded", "asset:data:geo:GSE30219 licence not read", "asset:data:geo:GSE50081 not downloaded", "asset:data:geo:GSE50081 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": "Kaplan-Meier survival analysis showed that high RRM2 expression was associated with poor prognosis (p = 7.86e-04), as shown in Figure 3A."}}, {"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": 0.7, "band": "medium", "quote": "Wilcoxon"}}, {"id": "method-3", "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-4", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {"p_value": "ession groups using the p-value determined in the log-r"}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-5", "family": "regression_modelling", "specific": "logistic", "label": "Regression modelling", "dsl_operations": ["glm_logit_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.7, "band": "medium", "quote": "logistic regression"}}, {"id": "method-6", "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 curve"}}], "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": ["GSE30219", "GSE50081"], "resolved_accessions": ["GSE30219", "GSE50081"], "statements": ["mRNA expression data (535 samples, Workflow Type: HTSeq-FPKM) and clinical information were downloaded from TCGA database (https://cancergenome.nih.gov). The following samples were excluded: (1) “0” gene expression value and (2) insufficient survival information. A total of 503 patients with LUAD with the corresponding clinical features were enrolled in this study."], "basis": "The paper names GSE30219, GSE50081 in GSE30219 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:33411689", "data:geo:GSE30219", "asset:table:pmid:33411689:1", "asset:table:pmid:33411689:2", "asset:table:pmid:33411689:3", "asset:table:pmid:33411689:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE30219"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:25:58Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 25163, "completion_tokens": 1748, "cached_tokens": 792}}, "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:33411689", "type": "paper", "label": "pmid:33411689"}, {"id": "source:pmid:33411689", "type": "manuscript", "label": "PMID 33411689 full text"}, {"id": "data:geo:GSE30219", "type": "dataset", "label": "GEO GSE30219"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33411689", "type": "paper", "label": "pmid:33411689"}, {"id": "source:pmid:33411689", "type": "manuscript", "label": "PMID 33411689 full text"}, {"id": "data:geo:GSE30219", "type": "dataset", "label": "GEO GSE30219"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33411689", "type": "extraction", "used": ["source:pmid:33411689"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE30219", "type": "accession_resolution", "used": ["data:geo:GSE30219"], "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:33411689", "parent_hash": "sha256:901bb0ed11ec204f8826e45ec1096ed54064c3c7db48b3ddef472c6d16d3937d", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE30219 licence not read", "asset:data:geo:GSE30219 not downloaded", "asset:data:geo:GSE50081 licence not read", "asset:data:geo:GSE50081 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": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["ay, DNA replication, small cell lung cancer, apoptosis, and pathways in cancer were differentially"], "order_basis": "paper_text_order:1846", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ang Uygur Autonomous Region Cell culture and transfection Human normal lung epithelial cell line (BEAS", "groups were constructed as follows: si-RRM2 transfected group (si-RRM2), RRM2 overexpressed group (O", "garded as a negative control (si-NC), and un-transfected group (O-Control). Transfection was performe", "i-NC), and un-transfected group (O-Control). Transfection was performed as described previously [50]."], "order_basis": "paper_text_order:3793", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["on (ATCC; Manassas, VA, USA). All cells were cultured in Dulbecco's Modified Eagle's medium (DMEM; Gi", ", except SPCA-1, PG49, and HaCaT, which were cultured in Roswell Park Memorial Institute-1640 (RPMI-1", "control), and human lung cancer cell lines (A549, SPCA-1, 95-D, and NCI-H292) were obtained f", "lidated by qRT-PCR. Finally, the transfected A549 lung cancer cells were collected for subsequ"], "order_basis": "paper_text_order:3959", "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": ["Kaplan-Meier survival analysis showed that high RRM2 expression was associated with poor prognosis (p = 7.86e-04), as shown in Figure 3A."], "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":"2026-11-04T02:36:48+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}}}