{"data":{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34220791", "kind": "science-record", "revision": 4, "content_hash": "sha256:87916d2470d2bd8c289f17f0de6e93afb385e7343b72882374fb831c5fe12952", "created_at": "2026-11-01T15:41:41Z", "updated_at": "2026-11-01T21:25:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Investigation of Genetic Determinants of Glioma Immune Phenotype by Integrative Immunogenomic Scale Analysis.", "doi": "10.3389/fimmu.2021.557994", "pmid": "34220791", "authors": ["Binghao Zhao", "Yuekun Wang", "Yaning Wang", "Congxin Dai", "Yu Wang", "Wenbin Ma"], "journal": "Frontiers in immunology", "year": 2021, "abstract": "The immunosuppressive mechanisms of the surrounding microenvironment and distinct immunogenomic features in glioblastoma (GBM) have not been elucidated to date. To fill this gap, useful data were extracted from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GSE16011, GSE43378, GSE23806, and GSE12907. With the ssGSEA method and the ESTIMATE and CIBERSORT algorithms, four microenvironmental signatures were used to identify glioma microenvironment genes, and the samples were reasonably classified into three immune phenotypes. The molecular and clinical features of these phenotypes were characterized via key gene set expression, tumor mutation burden, fraction of immune cell infiltration, and functional enrichment. Exhausted CD8+ T cell (GET) signature construction with the predictive response to commonly used antitumor drugs and peritumoral edema assisted in further characterizing the immune phenotype features. A total of 2,466 glioma samples with gene expression profiles were enrolled. Tumor purity, ESTIMATE, and immune and stromal scores served as the 4 microenvironment signatures used to classify gliomas into immune-high, immune-middle and immune-low groups, which had distinct immune heterogeneity and clinicopathological characteristics. The immune-H phenotype had higher expression of four immune signatures; however, most checkpoint molecules exhibited poor survival. Enriched pathways among the subtypes were related to immunity. The GET score was similar among the three phenotypes, while immune-L was more sensitive to bortezomib, cisplatin, docetaxel, lapatinib, and rapamycin prescriptions and displayed mild peritumor edema. The three novel immune phenotypes with distinct immunogenetic features could have utility for understanding glioma microenvironment regulation and determining prognosis. These results contribute to classifying glioma subtypes, remodeling the immunosuppressive microenvironment and informing novel cancer immunotherapy in the era of precision immuno-oncology.", "claims": [{"id": "claim-method", "statement": "Available clinicopathological factors (e.g., sex, age, treatment options, histological subtype, and classic mutations) were collected from the TCGA and CGGA datasets to estimate the association between these factors as well as the immune phenotypes and prognosis with univariable and multivariable Cox analysis (uniCox, multiCox) and proportional hazard models.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34220791", "locator": "sections[6] \"Survival Analysis\" paragraph 2", "quote": "Available clinicopathological factors (e.g., sex, age, treatment options, histological subtype, and classic mutations) were collected from the TCGA and CGGA datasets to estimate the association between these factors as well as the immune phenotypes and prognosis with univariable and multivariable Cox analysis (uniCox, multiCox) and proportional hazard models."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34220791", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. The original contributions presented in the study are included in the article/ Supplementary Material . 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE12907"], "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:GSE12907"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34220791", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2021.557994", "sha256": "sha256:b1e232d2650bded7c0920ccce06726b6a62bc643c9626bc417733cdf141fc3bd", "bytes": 50047, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2021.557994", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8242587", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12907", "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=GSE12907", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12907", "version": null, "note": "Publicly available datasets were analyzed in this study. The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. The original contributions presented in the study are included in the article/ Supplementary Material . 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The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. The original contributions presented in the study are included in the article/ Supplementary Material . 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patients from multiple cohorts.", "rows": [["", "Univariable Cox", "Multivariable Cox"], ["", "HR (95% CI)", "P-value", "HR (95% CI)", "P-value"], ["TCGA microarray cohort", "", "", "", ""], ["Gender (male vs. female)", "1.09 (0.87-1.35)", "0.457", "1.22 (0.98-1.53)", "0.080"], ["Radiation (yes vs. no)", "0.13 (0.09-0.18)", "< 0.001*", "0.15 (0.10-0.21)", "< 0.001*"], ["Chemotherapy (yes vs. no)", "0.43 (0.33-0.54)", "< 0.001*", "0.56 (0.43-0.72)", "< 0.001*"], ["Ethnicity (not Hispanic or Latino vs. Hispanic or Latino)", "0.90 (0.46-1.75)", "0.750", "0.87 (9,44-1.72)", "0.685"], ["Race", "", "", "", ""], ["White", "NA", "NA", "NA", "NA"], ["Asian", "0.97 (0.48-1.96)", "0.935", "1.05 (0.52-2.16)", "0.885"], ["Black or African American", "0.82 (0.54-1.24)", "0.350", "0.96 (0.63-1.46)", "0.845"], ["Phenotype", "", "", "", ""], ["Immune-L", "NA", "NA", "NA", "NA"], ["Immune-M", "0.82 (0.43-1.56)", "0.550", "0.68 (0.35-1.30)", "0.246"], ["Immune-H", "0.94 (0.49-1.79)", "0.849", "0.81 (0.42-1.55)", "0.525"], ["TCGA GBM RNA-seq cohort", "", "", "", ""], ["Age (y)", "", "", "", ""], ["< 50", "NA", "NA", "NA", "NA"], ["50-59", "1.26 (0.69-2.31)", "0.445", "1.37 (0.70-2.68)", "0.358"], ["60-69", "0.98 (0.56-1.72)", "0.944", "0.93 (0.48-1.80)", "0.831"], ["70-79", "1.97 (1.03-3.79)", "0.042*", "2.20 (1.01-4.79)", "0.048*"], ["Gender (male vs. female)", "0.89 (0.57-1.38)", "0.599", "1.19 (0.72-1.98)", "0.497"], ["Radiation (yes vs. no)", "0.31 (0.15-0.65)", "0.002*", "0.31 (0.10-0.94)", "0.039*"], ["Chemotherapy (yes vs. no)", "0.34 (0.18-0.66)", "0.002*", "0.76 (0.25-2.28)", "0.620"], ["Adjuvant TMZ chemotherapy (yes vs. no)", "0.64 (0.41-0.99)", "0.050*", "0.91 (0.53-1.58)", "0.746"], ["Histology type", "", "", "", ""], ["Proneural", "NA", "NA", "NA", "NA"], ["Neural", "0.94 (0.49-1.84)", "0.866", "0.96 (0.45-2.03)", "0.907"], ["Classical", "0.88 (0.44-1.52)", "0.534", "1.10 (0.54-2.24)", "0.794"], ["Mesenchymal", "0.99 (0.56-1.75)", "0.964", "0.92 (0.45-1.87)", "0.814"], ["Phenotype", "", "", "", ""], ["Immune-L", "NA", "NA", "NA", "NA"], ["Immune-M", "0.77 (0.28-2.13)", "0.619", "0.88 (0.30-2.59)", "0.817"], ["Immune-H", "1.68 (0.96-2.92)", "0.067", "2.00 (1.04-3.86)", "0.038*"], ["CGGA microarray cohort", "", "", "", ""], ["Age (y)", "", "", "", ""], ["< 50", "NA", "NA", "NA", "NA"], ["50-59", "2.80 (1.96-4.01)", "< 0.001*", "1.70 (1.13-2.55)", "0.011*"], ["60-69", "2.61 (1.67-4.08)", "< 0.001*", "1.60 (0.99-2.59)", "0.055"], ["70-79", "16.69 (2.24-)", "0.006*", "6.42 (0.77-53.42)", "0.085"], ["Gender (male vs. female)", "1.27 (0.94-1.72)", "0.125", "1.08 (0.78-1.49)", "0.640"], ["PRS type", "", "", "", ""], ["Primary", "NA", "NA", "NA", "NA"], ["Recurrent", "1.89 (1.11-3.22)", "0.020*", "2.19 (1.17-4.10)", "0.014*"], ["Secondary", "4.44 (2.25-8.77)", "< 0.001*", "2.83 (1.31-6.14)", "0.008*"], ["Histology (GBM vs. LGG)", "4.44 (3.24-6.09)", "< 0.001*", "4.69 (2.81-7.85)", "< 0.001*"], ["Grade", "", "", "", ""], ["WHO II", "NA", "NA", "NA", 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{"pmcid": "PMC8242587", "section_index": 20, "section_title": "Genomic Alterations, Tumor Mutation Burden, and Histological Characteristics", "row_count": 13, "column_count": 9}, "table": {"label": "Table 2", "caption": "Distribution of IDH status, type and grade of glioma among immune phenotypes in CGGA dataset.", "rows": [["", "", "Immune-L Phenotype", "Immune-M Phenotype", "Immune-H Phenotype", "Chi-square test (1)"], ["CGGA RNA-seq cohort", "IDH Status", "IDH MT(%)", "280 (72.0)", "IDH MT(%)", "203 (51.4)", "IDH MT(%)", "45 (25.3)", "χ2 = 110.855; P < 0.001"], ["IDH WT (%)", "109 (28.0)", "IDH WT (%)", "192 (48.6)", "IDH WT (%)", "133 (74.7)"], ["Glioma Type", "Primary (%)", "314 (77.0)", "Primary (%)", "249 (61.9)", "Primary (%)", "85 (49.7)", "χ2 = 45.058; P < 0.001"], ["Recurrent (%)", "94 (23.0)", "Recurrent (%)", "153 (38.1)", "Recurrent (%)", "86 (50.3)"], ["Glioma Grade", "LGG (%)", "322 (78.9)", "LGG (%)", "240 (59.9)", "LGG (%)", "61 (35.7)", "χ2 = 101.384; P < 0.001"], ["GBM (%)", "86 (21.1)", "GBM (%)", "161 (40.1)", "GBM (%)", "110 (64.3)"], ["CGGA microarray cohort", "IDH Status", "IDH MT(%)", "62 (59.6)", "IDH MT(%)", "47 (52.2)", "IDH MT(%)", "25 (23.8)", "χ2 = 29.941; P < 0.001"], ["IDH WT (%)", "42 (40.4)", "IDH WT (%)", "43 (47.8)", "IDH WT (%)", "80 (76.2)"], ["Glioma Type", "Primary (%)", "92 (91.1)", "Primary (%)", "83 (95.4)", "Primary (%)", "88 (88.9)", "χ2 = 2.625; P = 0.269"], ["Recurrent (%)", "9 (8.9)", "Recurrent (%)", "4 (4.6)", "Recurrent (%)", "11 (11.1)"], ["Glioma Grade", "LGG (%)", "82 (78.1)", "LGG (%)", "53 (58.9)", "LGG (%)", "39 (37.9)", "χ2 = 34.592; P < 0.001"], ["GBM (%)", "23 (21.9)", "GBM (%)", "38 (42.2)", "GBM (%)", "64 (62.1)"]], "row_count": 13, "column_count": 9, "numeric_cells": 43, "header_rows": 1, "locator": "section[20]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:34220791:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:62deb2fde6b74dcaa2a73c53bb13cfbf46a51cf420b5257dd680ebfbec28fb13", "bytes": 3770, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[22]/table-wrap[1]#T3", "version": null, "note": "Summary of the molecular and biological functions of T cell costimulatory molecules.", "structure": {"pmcid": "PMC8242587", "section_index": 22, "section_title": "Discussion", "row_count": 16, "column_count": 6}, "table": {"label": "Table 3", "caption": "Summary of the molecular and biological functions of T cell costimulatory molecules.", "rows": [["Molecular marker", "Aliase(s)", "Ligand(s)", "Receptor expression pattern", "Biological function", "Molecular function"], ["Coinhibitory", "", "", "", "", ""], ["PD-1", "PDCD1, CD279, SLEB2, hPD-1", "PD-L1, PD-L2", "Activated T cells, NK cells, NKT cells, B cells, macrophages, subsets of DCs", "Negative T cells costimulation (primarily in periphery), attenuate peripheral activity, preserve T-cell function in the context of chronic antigen", "Inhibition of proximal TCR signaling, attenuate CD28 signaling"], ["CTLA-4", "CD152, ALPS5, CELIAC3, GRD4", "B7-1 (CD80), B7-2 (CD86)", "Activated T cells, Tregs", "Negative T-cell costimulation (primarily at priming); prevent tonic signaling, attenuate high-affinity clones", "Competitive inhibition of CD28 costimulation (binding to B7-1 and B7-2)"], ["PD-L1", "CD274, PDCD1L1, B7-H, B7H1", "PD-1, B7-1 (CD80)", "Monocytes, macrophages, mast cells, inducible in DCs, T cells, B cells, NK cells", "Attenuate T cells activity in inflamed peripheral tissues", "PD-1 ligation; cell-intrinsic mechanism unclear"], ["LAG-3", "CD223, Ly66", "MHC-II, LSECtin", "Activated CD4+ and CD8+ T cells, NK cells, Tregs", "Negative regulator of T cells expansion; control T cells homeostasis; DCs activation", "Competitive binding to MHC-II; proximal LSECtin mechanism unclear"], ["TIM-3", "HAVCR2, CD366, KIM-3, SPTCL, TIMD-3", "Galectin-9, PtdSer, HMGB1, CEACAM-1", "Th1 CD4+ and Tc1 CD8+, Tregs, DCs, NK cells, monocytes", "Negative regulation of Type immunity; preserve peripheral tolerance", "Negative regulation ofproximal TCR components; differences between ligands unknown"], ["TIGIT", "VSIG9, VSTM3, WUCAM", "PVR (CD155), PVRL2 (CD112)", "CD4+ and CD8+ T cells, Tregs, TFH, NK cells", "Inhibition of T cells activity; DC tolerization", "Competitive inhibition of DNAM1 (CD226) costimulation (binding of PVR), binding of DNAM1 in cis; cell-intrinsic ITIM-negative signaling"], ["VISTA", "VSIR, B7-H5, B7H5, C10orf54, PD-1H", "Counterreceptor unknown", "T cells and activated Tregs, myeloid cells, mature APCs", "Negative regulation of T cells activity; suppression of CD4+ T cells, shaping naive CD4+ T cells compartment", "Increase threshold for TCR signaling, induce FOXP3 synthesis; proximal signaling unknown"], ["Costimulatory", "", "", "", "", ""], ["ICOS", "AILIM, CCLP, CRP-1", "ICOSL", "Activated T cells, B cells, ILC2", "Positive costimulation; Type I and II immunity; Tregs maintenance; TFH differentiation", "p50 PI3K recruitment (AKT signaling); enhance calcium signaling (PLCγ)"], ["OX40", "TNFRSF4, ACT35, CD134, TXGP1L", "OX40L", "Activated T cells, Tregs, NK cells, NKT cells, neutrophils", "Sustain and enhance CD4+ T cell immunity; role in CD8+ T cells and Tregs", "Regulation of BCL2/XL (survival); enhance PI3K/AKT signaling"], ["GITR", "TNFRSF18, AITR, CD357, ENERGEN, GITR", "GITRL", "Activated T cells, Tregs, B cells, NK cells, macrophages", "Attenuate Tregs; costimulation of activated T cells, NK cell activation", "Signal through TRAF5"], ["CD137", "TNFRSF9, 4-1BB, CDw137, ILA", "4-1BBL (CD137L)", "Activated T cells, Tregs, NK cells, monocytes, DCs, B cells", "Positive T cells costimulation; DC activation", "Signal through TRAF1, TRAF2"], ["CD40", "TNFRSF5, Bp50, CDW40, p50", "CD40L", "APCs, B cells, monocytes, non hematopoietic cells (e.g., fibroblasts, endothelial cells)", "APC licensing", "Signal through TRAF2, 3, 5, 6; TRAF-independent mechanisms unclear"], ["CD27", "TNFRSF7, S152, LPFS2, Tp55", "CD70", "CD4+ and CD8+ T cells, B cells, NK cells", "Lymphocyte and NK cell costimulation; generation of T-cell memory", "Signal through TRAF2, TRAF5"]], "row_count": 16, "column_count": 6, "numeric_cells": 34, "header_rows": 1, "locator": "section[22]/table-wrap[1]#T3"}}], "gaps": ["asset:data:geo:GSE12907 not downloaded", "asset:data:geo:GSE12907 licence not read", "asset:data:geo:GSE16011 not downloaded", "asset:data:geo:GSE16011 licence not read", "asset:data:geo:GSE23806 not downloaded", "asset:data:geo:GSE23806 licence not read", "asset:data:geo:GSE43378 not downloaded", "asset:data:geo:GSE43378 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "Univariable and multivariable Cox analysis with proportional hazard models", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Available clinicopathological factors (e.g., sex, age, treatment options, histological subtype, and classic mutations) were collected from the TCGA and CGGA datasets to estimate the association between these factors as well as the immune phenotypes and prognosis with univariable and multivariable Cox analysis (uniCox, multiCox) and proportional hazard models."}}], "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": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (Univariable and multivariable Cox analysis with proportional hazard models), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "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": ["GSE16011", "GSE43378", "GSE23806", "GSE12907"], "resolved_accessions": ["GSE16011", "GSE43378", "GSE23806", "GSE12907"], "statements": ["Publicly available datasets were analyzed in this study. The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE16011, GSE43378, GSE23806, GSE12907 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": [], "assets": ["source:pmid:34220791", "data:geo:GSE12907", "asset:table:pmid:34220791:1", "asset:table:pmid:34220791:2", "asset:table:pmid:34220791:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE12907"]}, "gaps": ["method:not_determinable"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:31:47Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 35123, "completion_tokens": 2598, "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:34220791", "type": "paper", "label": "pmid:34220791"}, {"id": "source:pmid:34220791", "type": "manuscript", "label": "PMID 34220791 full text"}, {"id": "data:geo:GSE12907", "type": "dataset", "label": "GEO GSE12907"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34220791", "type": "paper", "label": "pmid:34220791"}, {"id": "source:pmid:34220791", "type": "manuscript", "label": "PMID 34220791 full text"}, {"id": "data:geo:GSE12907", "type": "dataset", "label": "GEO GSE12907"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34220791", "type": "extraction", "used": ["source:pmid:34220791"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE12907", "type": "accession_resolution", "used": ["data:geo:GSE12907"], "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:34220791", "parent_hash": "sha256:e7eeb212a83c5a69456e8ada097111a9d72669d29956a4522f25e7918ad1d793", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE12907 licence not read", "asset:data:geo:GSE12907 not downloaded", "asset:data:geo:GSE16011 licence not read", "asset:data:geo:GSE16011 not downloaded", "asset:data:geo:GSE23806 licence not read", "asset:data:geo:GSE23806 not downloaded", "asset:data:geo:GSE43378 licence not read", "asset:data:geo:GSE43378 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"]},"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":"2026-11-04T02:47:01+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}}}