{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33540700", "kind": "science-record", "revision": 7, "content_hash": "sha256:4157023261099a3e7655e3ff011f3f8e976c29a98b90c5f206578d20828f1f98", "created_at": "2026-11-01T15:41:24Z", "updated_at": "2026-11-01T22:03:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma.", "doi": "10.3390/diagnostics11020219", "pmid": "33540700", "authors": ["Huan Luo", "Chao Ma"], "journal": "Diagnostics (Basel, Switzerland)", "year": 2021, "abstract": "BACKGROUND: Uveal melanoma (UM) is the most common intraocular tumor in adults. Ferroptosis is a newly recognized process of cell death, which is different from other forms of cell death in terms of morphology, biochemistry and genetics, and has played a vital role in cancer biology. The present research aimed to construct a gene signature from ferroptosis-related genes that have the prognostic capacity of UM.\nMETHODS: UM patients from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and GSE22138 from Gene Expression Omnibus (GEO) was treated as the validation cohort. A total of 103 ferroptosis-related genes were retrieved from the GeneCards. We performed Kaplan-Meier and univariate Cox analysis for preliminary screening of ferroptosis-related genes with potential prognostic capacity in the training cohort. These genes were then applied into an overall survival-based LASSO Cox regression model, constructing a gene signature. The discovered gene signature was then evaluated via Kaplan-Meier (KM), Cox, and ROC analyses in both cohorts. The Pearson correlation coefficient examined the correlations between risk score and UM common mutations and autophagy. The analyses of GSEA and immune infiltrating were performed to better study the functional annotation of the gene signature and the character of each kind of immune cell in the tumor microenvironment.\nRESULTS: A seven-gene signature was found from the training cohort and validated in all cohorts by Kaplan-Meier and Cox regression analyses, revealing its independent prognosis value in UM. Moreover, ROC analysis was conducted, confirming the strong predictive ability that this signature had for UM prognosis. A total of 52.24% (256/490) autophagy-related genes were significantly correlated with risk scores. Analyses of GSEA and immune infiltrating detailed exhibited specific pathways associated with the seven-gene signature, also confirming the crucial role that Mast cells resting played in the prognosis of the seven-gene signature.\nCONCLUSIONS: In this study, a novel ferroptosis-related seven-gene signature (ALOX12, CD44, MAP1LC3C, STEAP3, HMOX1, ITGA6, and AIFM2/FSP1) was built. It could accurately predict UM prognosis and was related to Mast cells resting, which provides the potential for personalized outcome prediction and the development of new therapies in the UM population.", "claims": [{"id": "claim-data-access", "statement": "The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33540700", "locator": "sections[26] \"Data Availability Statement\" paragraph 2", "quote": "The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138."}], "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:33540700"], "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:GSE22138"], "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:GSE22138"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33540700", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/diagnostics11020219", "sha256": "sha256:1de0e604bb86b57426562a126f54604e7fb8662521e7acffcc93a2a677a1ef68", "bytes": 60758, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/diagnostics11020219", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7913108", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE22138", "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=GSE22138", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE22138", "version": null, "note": "The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM550623", "GSM550624", "GSM550625", "GSM550626", "GSM550627", "GSM550628", "GSM550629", "GSM550630", "GSM550631", "GSM550632", "GSM550633", "GSM550634", "GSM550635", "GSM550636", "GSM550637", "GSM550638", "GSM550639", "GSM550640", "GSM550641", "GSM550642", "GSM550643", "GSM550644", "GSM550645", "GSM550646", "GSM550647", "GSM550648", "GSM550649", "GSM550650", "GSM550651", "GSM550652", "GSM550653", "GSM550654", "GSM550655", "GSM550656", "GSM550657", "GSM550658", "GSM550659", "GSM550660", "GSM550661", "GSM550662", "GSM550663", "GSM550664", "GSM550665", "GSM550666", "GSM550667", "GSM550668", "GSM550669", "GSM550670", "GSM550671", "GSM550672", "GSM550673", "GSM550674", "GSM550675", "GSM550676", "GSM550677", "GSM550678", "GSM550679", "GSM550680", "GSM550681", "GSM550682", "GSM550683", "GSM550684", "GSM550685"], "sample_count": 63, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression Data from Uveal Melanoma primary tumors.", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33540700:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0b3c227e3462aae8f656073dbe0b9f974a1a651881ca3cec01324a63fa08a394", "bytes": 2864, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#diagnostics-11-00219-t001", "version": null, "note": "Clinical characteristics of patients involved in the study.", "structure": {"pmcid": "PMC7913108", "section_index": 11, "section_title": "3.1. Characteristics of UMs", "row_count": 80, "column_count": 4}, "table": {"label": "Table 1", "caption": "Clinical characteristics of patients involved in the study.", "rows": [["Characteristics", "Training Cohort (TCGA-UVM, 80 Cases)", "Validation Cohort (GSE22138, 63 Cases)"], ["age", "", "", ""], ["", "<65", "45(56.25%)", "36(57.14%)"], ["", "≥65", "35(43.75%)", "27(42.86%)"], ["gender", "", ""], ["", "female", "35(43.75%)", "24(38.1%)"], ["", "male", "45(56.25%)", "39(61.9%)"], ["T classification", "", ""], ["", "T1", "0", "NA"], ["", "T2", "4(5%)", "NA"], ["", "T3", "36(45%)", "NA"], ["", "T4", "38(47.5%)", "NA"], ["", "unknown", "2(2.5%)", "NA"], ["M classification", "", ""], ["", "M0", "73(91.25%)", "28(44.44%)"], ["", "M1", "3(3.75%)", "35(55.56%)"], ["", "unknown", "4(5%)", "0"], ["tumor stage", "", ""], ["", "stage I", "0", "NA"], ["", "stage II", "36(45%)", "NA"], ["", "stage III", "40(50%)", "NA"], ["", "stage IV", "4(5%)", "NA"], ["extrascleral extension", "", ""], ["", "yes", "7(8.75%)", "5(7.94%)"], ["", "no", "68(85%)", "48(76.19%)"], ["", "unknown", "5(6.25%)", "10(15.87%)"], ["tumor diameter, mm", "", ""], ["", "<20", "60(75%)", "44(69.84%)"], ["", "≥20", "19(23.75%)", "9(14.29%)"], ["", "unknown", "1(1.25%)", "10(15.87%)"], ["tumor thickness, mm", "", ""], ["", "<10", "29(36.25%)", "10(15.87%)"], ["", "≥10", "51(63.75%)", "53(84.13%)"], ["tumor eye side", "", ""], ["", "left", "NA", "33(52.38%)"], ["", "right", "NA", "30(47.62%)"], ["tumor location", "", ""], ["", "all over the eye", "NA", "1(1.59%)"], ["", "anterior to equator", "NA", "3(4.76%)"], ["", "on equator", "NA", "42(66.67%)"], ["", "posterior and on equator", "NA", "3(4.76%)"], ["", "posterior to equator", "NA", "9(14.29%)"], ["", "unknown", "NA", "5(7.94%)"], ["tumor cell type", "", ""], ["", "epithelioid", "NA", "21(33.33%)"], ["", "mixed", "NA", "23(36.51%)"], ["", "unknown", "NA", "19(30.16%)"], ["eye color", "", ""], ["", "blue", "9(11.25%)", "NA"], ["", "brown", "15(18.75%)", "NA"], ["", "green", "6(7.5%)", "NA"], ["", "unknown", "50(62.5%)", "NA"], ["person neoplasm cancer status", "", ""], ["", "with tumor", "9(11.25%)", "NA"], ["", "tumor free", "56(70%)", "NA"], ["", "unknown", "15(18.75%)", "NA"], ["radiation therapy", "", ""], ["", "yes", "3(3.75%)", "NA"], ["", "no", "63(78.75%)", "NA"], ["", "unknown", "14(17.5%)", "NA"], ["ethnicity", "", ""], ["", "hispanic or latino", "1(1.25%)", "NA"], ["", "not hispanic or latino", "52(65%)", "NA"], ["", "unknown", "27(33.75%)", "NA"], ["tissue or organ of origin diagnosis", "", ""], ["", "choroid", "67(83.75%)", "NA"], ["", "ciliary body", "5(6.25%)", "NA"], ["", "overlapping lesion of eye and adnexa", "8(10%)", "NA"], ["retinal detachment", "", ""], ["", "yes", "NA", "36(57.14%)"], ["", "no", "NA", "22(34.92%)"], ["", "unknown", "NA", "5(7.94%)"], ["mitotic count", "", ""], ["", "<20", "42(52.5%)", "NA"], ["", "≥20", "11(13.75%)", "NA"], ["", "unknown", "27(33.75%)", "NA"], ["chromosome 3 status", "", ""], ["", "disomy", "NA", "18(28.57%)"], ["", "monosomy", "NA", "37(58.73%)"], ["", "unknown", "NA", "8(12.7%)"]], "row_count": 80, "column_count": 4, "numeric_cells": 86, "header_rows": 1, "locator": "section[11]/table-wrap[1]#diagnostics-11-00219-t001"}}, {"id": "asset:table:pmid:33540700:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f75388708eb2399e0e5782ec607aae68f4a4290b14ff7841c2cad6c6ecd4aabf", "bytes": 3624, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#diagnostics-11-00219-t002", "version": null, "note": "22 ferroptosis-related potential prognostic genes generated from the training cohort.", "structure": {"pmcid": "PMC7913108", "section_index": 12, "section_title": "3.2. Identification of Prognostic Ferroptosis-Related Gene Signature", "row_count": 24, "column_count": 9}, "table": {"label": "Table 2", "caption": "22 ferroptosis-related potential prognostic genes generated from the training cohort.", "rows": [["Gene Symbol", "Description", "Category", "Genomic Location", "Kaplan–Meier Analysis (p-Value)", "Univariate Cox Regression Analysis"], ["HR", "HR_95L", "HR_95H", "p-Value"], ["VDAC1", "Voltage Dependent Anion Channel 1", "Protein Coding", "chr5", "7.12 × 10−6", "5.291343594", "1.781142996", "15.71929771", "2.71 × 10−3"], ["STEAP3", "STEAP3 Metalloreductase", "Protein Coding", "chr2", "3.19 × 10−3", "4.206162616", "2.092921898", "8.453160136", "5.49 × 10−5"], ["SLC39A8", "Solute Carrier Family 39 Member 8", "Protein Coding", "chr4", "3.77 × 10−2", "3.869852511", "1.326333156", "11.29109861", "1.33 × 10−2"], ["SLC11A2", "Solute Carrier Family 11 Member 2", "Protein Coding", "chr12", "4.76 × 10−3", "3.094601274", "1.570769273", "6.096730571", "1.09 × 10−3"], ["PEBP1", "Phosphatidylethanolamine Binding Protein 1", "Protein Coding", "chr12", "4.86 × 10−2", "0.234529606", "0.075635069", "0.727230595", "1.20 × 10−2"], ["MAPK1", "Mitogen−Activated Protein Kinase 1", "Protein Coding", "chr22", "9.03 × 10−3", "2.895607401", "1.163501743", "7.206299663", "2.23 × 10−2"], ["MAP1LC3C", "Microtubule Associated Protein 1 Light Chain 3 Gamma", "Protein Coding", "chr1", "1.31 × 10−2", "0.459748503", "0.271733125", "0.777853955", "3.78 × 10−3"], ["LINC00472", "Long Intergenic Non-Protein Coding RNA 472", "RNA Gene", "chr6", "6.36 × 10−3", "0.043258919", "0.003322917", "0.563160037", "1.65 × 10−2"], ["ITGA6", "Integrin Subunit Alpha 6", "Protein Coding", "chr2", "1.13 × 10−3", "4.613594536", "2.148024539", "9.909223176", "8.85 × 10−5"], ["HSPA5", "Heat Shock Protein Family A (Hsp70) Member 5", "Protein Coding", "chr9", "8.91 × 10−3", "2.25326069", "1.228917946", "4.131426149", "8.63 × 10−3"], ["HMOX1", "Heme Oxygenase 1", "Protein Coding", "chr22", "2.19 × 10−3", "2.334473768", "1.59857086", "3.409149952", "1.14 × 10−5"], ["GSS", "Glutathione Synthetase", "Protein Coding", "chr20", "3.31 × 10−3", "3.851728269", "1.85357871", "8.003874117", "3.02 × 10−4"], ["FTH1", "Ferritin Heavy Chain 1", "Protein Coding", "chr11", "4.64 × 10− 3", "4.040699109", "1.10619952", "14.75976891", "3.46 × 10−2"], ["CD44", "CD44 Molecule (Indian Blood Group)", "Protein Coding", "chr11", "6.66 × 10− 3", "0.304760194", "0.142947413", "0.649740862", "2.10 × 10−3"], ["CASP8", "Caspase 8", "Protein Coding", "chr2", "3.91 × 10−2", "2.604965341", "1.209052632", "5.612530215", "1.45 × 10−2"], ["BAP1", "BRCA1 Associated Protein 1", "Protein Coding", "chr3", "1.40 × 10−6", "0.561778701", "0.412394493", "0.765275275", "2.56 × 10−4"], ["AURKA", "Aurora Kinase A", "Protein Coding", "chr20", "2.54 × 10−2", "3.390492663", "1.565174215", "7.344511806", "1.96 × 10−3"], ["ANO6", "Anoctamin 6", "Protein Coding", "chr12", "2.56 × 10−2", "2.263254914", "1.292723147", "3.962428319", "4.26 × 10−3"], ["ALOX12", "Arachidonate 12-Lipoxygenase, 12S Type", "Protein Coding", "chr17", "1.48 × 10−3", "0.022909689", "0.002539428", "0.20668188", "7.66 × 10−4"], ["AIFM2/FSP1", "Apoptosis Inducing Factor Mitochondria Associated 2", "Protein Coding", "chr10", "6.03 × 10−6", "6.104896507", "2.780109603", "13.40586045", "6.55 × 10−6"], ["ACSL6", "Acyl-CoA Synthetase Long Chain Family Member 6", "Protein Coding", "chr5", "4.56 × 10−4", "2.283441779", "1.099533069", "4.742109633", "2.68 × 10−2"], ["ACSL1", "Acyl-CoA Synthetase Long Chain Family Member 1", "Protein Coding", "chr4", "6.64 × 10−3", "1.873686292", "1.236619189", "2.838950221", "3.06 × 10−3"]], "row_count": 24, "column_count": 9, "numeric_cells": 147, "header_rows": 2, "locator": "section[12]/table-wrap[1]#diagnostics-11-00219-t002"}}, {"id": "asset:table:pmid:33540700:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:58c27e8d0165e8f86a9b747fd69d80eaba41c2b48e51986235ea562936048c61", "bytes": 928, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#diagnostics-11-00219-t003", "version": null, "note": "7 ferroptosis-related prognostic genes obtained from LASSO Cox regression model.", "structure": {"pmcid": "PMC7913108", "section_index": 12, "section_title": "3.2. Identification of Prognostic Ferroptosis-Related Gene Signature", "row_count": 8, "column_count": 4}, "table": {"label": "Table 3", "caption": "7 ferroptosis-related prognostic genes obtained from LASSO Cox regression model.", "rows": [["Gene Symbol", "Description", "Role", "Risk Coefficient"], ["STEAP3", "STEAP3 Metalloreductase", "Marker [26]", "0.055060532"], ["MAP1LC3C", "Microtubule Associated Protein 1 Light Chain 3 Gamma", "Driver [27]", "−0.202884346"], ["ITGA6", "Integrin Subunit Alpha 6", "Suppressor [28]", "0.34461317"], ["HMOX1", "Heme Oxygenase 1", "Driver [29,30,31,32], Suppressor [33,34], Marker [35,36]", "0.125266141"], ["CD44", "CD44 Molecule (Indian Blood Group)", "Suppressor [37]", "−0.316011897"], ["ALOX12", "Arachidonate 12-Lipoxygenase, 12S Type", "Driver [38,39,40], Marker [41]", "−1.311120914"], ["AIFM2/FSP1", "Apoptosis Inducing Factor Mitochondria Associated 2", "Suppressor [42,43]", "0.710789029"]], "row_count": 8, "column_count": 4, "numeric_cells": 22, "header_rows": 1, "locator": "section[12]/table-wrap[2]#diagnostics-11-00219-t003"}}, {"id": "asset:table:pmid:33540700:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b9d6a1eb3e5b07fea8c9fdd5e38c27d5f3dac16cc113425a84f0e0312bd79e3e", "bytes": 5193, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#diagnostics-11-00219-t004", "version": null, "note": "Univariate analysis and multivariate analysis of the correlation of gene-signature risk score with outcomes among uveal melanoma patients in two cohorts.", "structure": {"pmcid": "PMC7913108", "section_index": 13, "section_title": "3.3. The Prognostic Capacity of the Seven-Gene Signature", "row_count": 46, "column_count": 9}, "table": {"label": "Table 4", "caption": "Univariate analysis and multivariate analysis of the correlation of gene-signature risk score with outcomes among uveal melanoma patients in two cohorts.", "rows": [["Variable", "Univariate Cox Analysis", "Multivariate Cox Analysis"], ["Coef", "HR (95% CI)", "z", "p-Value", "Coef", "HR (95% CI)", "z", "p-Value"], ["TCGA-UVM (overall survival) *", "", "", "", "", "", "", "", ""], ["age", "0.0447", "1.05 (1.01–1.09)", "2.35", "0.0186", "0.101", "1.11 (0.976–1.25)", "1.57", "0.115"], ["gender (male vs. female)", "0.433", "1.54 (0.651–3.65)", "0.984", "0.325", "", "", "", ""], ["tumor stage (stage III vs. stage II)", "0.336", "1.4 (0.556–3.52)", "0.713", "0.476", "−3.06", "0.047 (0.00199–1.11)", "−1.9", "0.0579"], ["tumor stage (stage IV vs. stage II)", "4.37", "79.3 (7.55–834)", "3.64", "0.000269", "NA", "NA", "NA", "NA"], ["extrascleral extension (yes vs. no)", "1.54", "4.64 (1.5–14.4)", "2.66", "0.00774", "−4.25", "0.0142 (3.98× 10−13–5.1× 10 8)", "−0.343", "0.732"], ["tumor diameter", "0.155", "1.17 (1.01–1.35)", "2.12", "0.0344", "0.723", "2.06 (1.11–3.83)", "2.29", "0.0221"], ["tumor thickness", "0.111", "1.12 (0.949–1.32)", "1.33", "0.183", "", "", "", ""], ["radiation therapy (yes vs. no)", "1.68", "5.35 (1.09–26.3)", "2.07", "0.0389", "7.79", "2410 (4.34 × 10−8–1.33 × 10 14)", "0.617", "0.537"], ["ethnicity (hispanic or latino vs. not hispanic or latino)", "−16", "1.09 × 10−7 (0-Inf)", "−0.00205", "0.998", "", "", "", ""], ["tissue or organ of origin diagnosis (choroid vs. not choroid)", "−0.286", "0.751 (0.254–2.22)", "−0.517", "0.605", "", "", "", ""], ["mitotic count", "−0.0119", "0.988 (0.931–1.05)", "−0.394", "0.693", "", "", "", ""], ["chromosome 3 copy number", "−1.86", "0.156 (0.0574–0.422)", "−3.65", "0.00026", "2.76", "15.9 (0.894–281)", "1.88", "0.0597"], ["chromosome 6p copy number", "−1.06", "0.348 (0.176–0.687)", "−3.04", "0.00237", "−0.874", "0.417 (0.0559–3.11)", "−0.852", "0.394"], ["chromosome 8q copy number", "0.516", "1.67 (1.27–2.2)", "3.68", "0.000235", "−0.88", "0.415 (0.126–1.37)", "−1.44", "0.149"], ["risk score", "1.65", "5.22 (2.59–10.5)", "4.61", "3.99 × 10−6", "4.23", "68.6 (3.36–1400)", "2.75", "0.00598"], ["TCGA-UVM (progression-free survival) #", "", "", "", "", "", "", "", ""], ["age", "0.0271", "1.03 (0.996–1.06)", "1.7", "0.0886", "", "", "", ""], ["gender (male vs. female)", "−0.139", "0.87 (0.422–1.8)", "−0.376", "0.707", "", "", "", ""], ["tumor stage (stage III vs. stage II)", "0.381", "1.46 (0.665–3.22)", "0.946", "0.344", "−0.959", "0.383 (0.094–1.56)", "−1.34", "0.181"], ["tumor stage (stage IV vs. stage II)", "3.31", "27.4 (5.06–149)", "3.84", "0.000124", "2.87", "17.6 (0.677–455)", "1.73", "0.0845"], ["extrascleral extension (yes vs. no)", "1.45", "4.26 (1.57–11.5)", "2.85", "0.0044", "−0.682", "0.506 (0.00917–27.9)", "−0.333", "0.739"], ["tumor diameter", "0.113", "1.12 (0.999–1.25)", "1.94", "0.0527", "", "", "", ""], ["tumor thickness", "0.00859", "1.01 (0.875–1.16)", "0.119", "0.905", "", "", "", ""], ["radiation therapy (yes vs. no)", "0.0846", "1.09 (0.142–8.33)", "0.0814", "0.935", "", "", "", ""], ["ethnicity (hispanic or latino vs. not hispanic or latino)", "−17", "3.98 × 10−8 (0-Inf)", "−0.00217", "0.998", "", "", "", ""], ["tissue or organ of origin diagnosis (choroid vs. not choroid)", "0.0872", "1.09 (0.377–3.16)", "0.161", "0.872", "", "", "", ""], ["mitotic count", "0.0545", "1.06 (1.01–1.1)", "2.64", "0.00829", "0.0575", "1.06 (0.976–1.15)", "1.37", "0.17"], ["chromosome 3 copy number", "−1.86", "0.156 (0.0631–0.386)", "−4.02", "5.88 × 10−5", "−1.3", "0.272 (0.0293–2.52)", "−1.15", "0.252"], ["chromosome 6p copy number", "−0.628", "0.534 (0.321–0.888)", "−2.42", "0.0155", "0.709", "2.03 (0.611–6.75)", "1.16", "0.247"], ["chromosome 8q copy number", "0.521", "1.68 (1.31–2.16)", "4.08", "4.56 × 10−5", "0.146", "1.16 (0.546–2.45)", "0.381", "0.703"], ["risk score", "0.933", "2.54 (1.65–3.91)", "4.25", "2.13 × 10−5", "0.703", "2.02 (0.486–8.39)", "0.967", "0.0334"], ["GSE22138 (metastasis-free survival) &", "", "", "", "", "", "", "", ""], ["age", "0.0213", "1.02 (0.995–1.05)", "1.59", "0.113", "", "", "", ""], ["gender (male vs. female)", "0.353", "1.42 (0.714–2.84)", "1", "0.316", "", "", "", ""], ["tumor eye side (left vs. right)", "−0.193", "0.824 (0.424–1.6)", "−0.57", "0.569", "", "", "", ""], ["tumor location (on equator vs. others)", "−0.325", "0.723 (0.357–1.46)", "−0.903", "0.366", "", "", "", ""], ["tumor diameter", "−0.0165", "0.984 (0.893–1.08)", "−0.336", "0.737", "", "", "", ""], ["tumor thickness", "0.116", "1.12 (0.951–1.33)", "1.37", "0.171", "", "", "", ""], ["tumor cell type (epithelioid vs. mixed)", "0.753", "2.12 (0.954–4.72)", "1.85", "0.0649", "", "", "", ""], ["retinal detachment (yes vs. no)", "1.06", "2.87 (1.24–6.68)", "2.45", "0.0142", "0.857", "2.36 (0.981–5.66)", "1.92", "0.0553"], ["extrascleral extension (yes vs. no)", "0.563", "1.76 (0.668–4.62)", "1.14", "0.253", "", "", "", ""], ["chromosome 3 status (monosomy vs. disomy)", "1.67", "5.29 (1.82–15.3)", "3.07", "0.00217", "1.24", "3.45 (1.04–11.5)", "2.02", "0.0435"], ["risk score", "0.646", "1.91 (1.31–2.78)", "3.37", "0.000745", "0.523", "1.69 (1.03–2.77)", "2.07", "0.0388"]], "row_count": 46, "column_count": 9, "numeric_cells": 254, "header_rows": 2, "locator": "section[13]/table-wrap[1]#diagnostics-11-00219-t004"}}], "gaps": ["asset:data:geo:GSE22138 not downloaded", "asset:data:geo:GSE22138 licence not read"]}, "analysis": {"state": "complete", "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": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-2", "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-3", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pearson correlation"}}, {"id": "method-4", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.7, "band": "medium", "quote": "ROC analysis"}}], "targets": [], "gaps": []}, "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": ["GSE22138"], "resolved_accessions": ["GSE22138"], "statements": ["The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138."], "basis": "The paper names GSE22138 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": ["survival_km"], "assets": ["source:pmid:33540700", "data:geo:GSE22138", "asset:table:pmid:33540700:1", "asset:table:pmid:33540700:2", "asset:table:pmid:33540700:3", "asset:table:pmid:33540700:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE22138"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:23:57Z", "independence": "single_reader"}, "evidence_check": {"method": "absent", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 50138, "completion_tokens": 1491, "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:33540700", "type": "paper", "label": "pmid:33540700"}, {"id": "source:pmid:33540700", "type": "manuscript", "label": "PMID 33540700 full text"}, {"id": "data:geo:GSE22138", "type": "dataset", "label": "GEO GSE22138"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33540700", "type": "paper", "label": "pmid:33540700"}, {"id": "source:pmid:33540700", "type": "manuscript", "label": "PMID 33540700 full text"}, {"id": "data:geo:GSE22138", "type": "dataset", "label": "GEO GSE22138"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33540700", "type": "extraction", "used": ["source:pmid:33540700"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE22138", "type": "accession_resolution", "used": ["data:geo:GSE22138"], "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:33540700", "parent_hash": "sha256:f8b66e2f0fe087d2be08c948190e97c44b6ce4e093b6ce49ef9d0c87e0190014", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE22138 licence not read", "asset:data:geo:GSE22138 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": 0.7, "evidence": ["Kaplan-Meier"], "order_basis": "analysis_only", "id": "assay:1"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T00:31:44+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}}}