{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29682089", "kind": "science-record", "revision": 7, "content_hash": "sha256:0501b4e4d4b2f4ed09bfc4ecbef9e5cf9b8812437bff64644df8e0a87b8ff4d6", "created_at": "2026-11-01T15:40:33Z", "updated_at": "2026-11-01T21:59:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Large-scale analysis of DFNA5 methylation reveals its potential as biomarker for breast cancer.", "doi": "10.1186/s13148-018-0479-y", "pmid": "29682089", "authors": ["Lieselot Croes", "Matthias Beyens", "Erik Fransen", "Joe Ibrahim", "Wim Vanden Berghe", "Arvid Suls", "Marc Peeters", "Patrick Pauwels", "Guy Van Camp", "Ken Op de Beeck"], "journal": "Clinical epigenetics", "year": 2018, "abstract": "Background: Breast cancer is the most frequent cancer among women worldwide. Biomarkers for early detection and prognosis of these patients are needed. We hypothesized that deafness, autosomal dominant 5 (DFNA5) may be a valuable biomarker, based upon strong indications for its role as tumor suppressor gene and its function in regulated cell death. In this study, we aimed to analyze DFNA5 methylation and expression in the largest breast cancer cohort to date using publicly available data from TCGA, in order to further unravel the role of DFNA5 as detection and/or prognostic marker in breast cancer. We analyzed Infinium HumanMethylation450k data, covering 22 different CpGs in the DFNA5 gene (668 breast adenocarcinomas and 85 normal breast samples) and DFNA5 expression (Agilent 244K Custom Gene Expression: 476 breast adenocarcinomas and 56 normal breast samples; RNA-sequencing: 666 breast adenocarcinomas and 71 normal breast samples).\nResults: DFNA5 methylation and expression were significantly different between breast cancer and normal breast samples. Overall, breast cancer samples showed higher DFNA5 methylation in the putative gene promoter compared to normal breast samples, whereas in the gene body and upstream of the putative gene promoter, the opposite is true. Furthermore, DFNA5 methylation, in 10 out of 22 CpGs, and expression were significantly higher in lobular compared to ductal breast cancers. An important result of this study was the identification of a combination of one CpG in the gene promoter (CpG07504598) and one CpG in the gene body (CpG12922093) of DFNA5, which was able to discriminate between breast cancer and normal breast samples (AUC = 0.93). This model was externally validated in three independent datasets. Moreover, we showed that estrogen receptor state is associated with DFNA5 methylation and expression. Finally, we were able to find a significant effect of DFNA5 gene body methylation on a 5-year overall survival time.\nConclusions: We conclude that DFNA5 methylation shows strong potential as detection and prognostic biomarker for breast cancer.", "claims": [{"id": "claim-method", "statement": "Cox proportional hazard models were fit using the survival package [42], to model 5-year overall survival (OS) time based upon either DFNA5 methylation or DFNA5 expression (microarray or RNA-seq), accounting for age.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29682089", "locator": "sections[8] \"Statistical analysis\" paragraph 4", "quote": "Cox proportional hazard models were fit using the survival package [42], to model 5-year overall survival (OS) time based upon either DFNA5 methylation or DFNA5 expression (microarray or RNA-seq), accounting for age."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed during the current study are available in the following open access repositories:TCGA, https://cancergenome.nih.gov/GEO, https://www.ncbi.nlm.nih.gov/geo/ (GEO accession numbers: GSE52865, GSE69914 and GSE60185)miRTarBase, http://mirtarbase.mbc.nctu.edu.tw/index.php.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29682089", "locator": "sections[23] \"ack\" paragraph 1", "quote": "The datasets analyzed during the current study are available in the following open access repositories:TCGA, https://cancergenome.nih.gov/GEO, https://www.ncbi.nlm.nih.gov/geo/ (GEO accession numbers: GSE52865, GSE69914 and GSE60185)miRTarBase, http://mirtarbase.mbc.nctu.edu.tw/index.php."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using publicly available TCGA data and linear mixed models that accounted for batch effects, the study found that a two-CpG DFNA5 methylation model discriminated breast adenocarcinoma from normal breast samples with an AUC of 0.93 and was externally validated in three independent datasets.", "kind": "quantitative", "target": {"value": 0.93, "unit": "auc", "tolerance": null, "source": "An important result of this study was the identification of a combination of one CpG in the gene promoter (CpG07504598) and one CpG in the gene body (CpG12922093) of DFNA5, which was able to discriminate between breast cancer and normal breast samples (AUC = 0.93)."}, "evidence": [{"asset": "source:pmid:29682089", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In this study, we aimed to analyze DFNA5 methylation and expression in the largest breast cancer cohort to date using publicly available data from TCGA, in order to further unravel the role of DFNA5 as detection and/or prognostic marker in breast cancer."}, {"asset": "source:pmid:29682089", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "An important result of this study was the identification of a combination of one CpG in the gene promoter (CpG07504598) and one CpG in the gene body (CpG12922093) of DFNA5, which was able to discriminate between breast cancer and normal breast samples (AUC = 0.93)."}, {"asset": "source:pmid:29682089", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "This model was externally validated in three independent datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using publicly available TCGA data and linear mixed models that accounted for batch effects, the study found that a two-CpG DFNA5 methylation model discriminated breast adenocarcinoma from normal breast samples with an AUC of 0.93 and was externally validated in three independent datasets.", "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:29682089"], "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:GSE52865"], "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:GSE52865"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29682089", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13148-018-0479-y", "sha256": 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"GSM1712749", "GSM1712750", "GSM1712751", "GSM1712752", "GSM1712753", "GSM1712754", "GSM1712755", "GSM1712756", "GSM1712758", "GSM1712760", "GSM1712763", "GSM1712766", "GSM1712767", "GSM1712768", "GSM1712769", "GSM1712770", "GSM1712771", "GSM1712772", "GSM1712773", "GSM1712774", "GSM1712775", "GSM1712776", "GSM1712777", "GSM1712778", "GSM1712779"], "sample_count": 407, "group_sizes": null, "group_sizes_basis": null, "platform": "16304", "taxon": "Homo sapiens", "title": "Genome wide DNA methylation profiling of normal breast, normal adjacent and breast cancer tissue", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:29682089:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:28447f004527778a3bd111b6c23d6c80735750c911b1a7cdfa0f02efef056d32", "bytes": 1691, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#Tab1", "version": null, "note": "Clinicopathological features of the TCGA breast adenocarcinomas", "structure": {"pmcid": "PMC5896072", "section_index": 3, "section_title": "Study population and tissue samples", "row_count": 23, "column_count": 7}, "table": {"label": "Table 1", "caption": "Clinicopathological features of the TCGA breast adenocarcinomas", "rows": [["Clinicopathological parameter", "Methylation (N = 668)", "Expression–microarray (N = 476)", "Expression–RNA-seq (N = 666)"], ["Number (%)", "P value (range)", "Number (%)", "P value", "Number (%)", "P value"], ["ER", "", "2.2 × 10−22–0.049 (20/22 CpGs)", "", "0.038", "", "3.3 × 10− 3"], ["ER+", "490 (73.3)", "", "362 (76.0)", "", "488 (73.3)", ""], ["ER−", "142 (21.3)", "", "107 (22.5)", "", "142 (21.3)", ""], ["Unknown", "36 (5.4)", "", "7 (1.5)", "", "36 (5.4)", ""], ["PR", "", "9.7 × 10−15–3.0 × 10−3 (15/22 CpGs)", "", "N.S.", "", "N.S."], ["PR+", "428 (64.1)", "", "310 (65.1)", "", "427 (64.1)", ""], ["PR−", "201 (30.1)", "", "158 (33.2)", "", "200 (30.0)", ""], ["Unknown", "39 (5.8)", "", "8 (1.7)", "", "39 (5.9)", ""], ["HER2", "", "0.023 (1/22 CpGs)", "", "N.S.", "", "N.S."], ["HER2+", "32 (4.8)", "", "45 (9.4)", "", "32 (4.8)", ""], ["HER2−", "195 (29.2)", "", "166 (34.9)", "", "195 (29.3)", ""], ["Unknown", "441 (66.0)", "", "265 (55.7)", "", "439 (65.9)", ""], ["Tumor stage", "", "1.9 × 10−4–0.020 (5/22 CpGs)", "", "N.S.", "", "N.S."], ["I", "109 (16.3)", "", "83 (17.5)", "", "107 (16.1)", ""], ["II", "378 (56.6)", "", "269 (56.5)", "", "378 (56.8)", ""], ["III", "166 (24.9)", "", "99 (20.8)", "", "166 (24.9)", ""], ["IV", "9 (1.3)", "", "12 (2.5)", "", "9 (1.3)", ""], ["Unknown", "6 (0.9)", "", "13 (2.7)", "", "6 (0.9)", ""], ["Histological diagnosis", "", "1.0 × 10−4–0.038 (10/22 CpGs)", "", "4.2 × 10−4", "", "3.2 × 10−4"], ["Ductal", "496 (74.3)", "", "435 (91.4)", "", "494 (74.2)", ""], ["Lobular", "172 (25.7)", "", "41 (8.6)", "", "172 (25.8)", ""]], "row_count": 23, "column_count": 7, "numeric_cells": 60, "header_rows": 2, "locator": "section[3]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:29682089:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cddc5c0cb6a2bdcd2317f657c8b8792be1f3579ede6fb1c5d425e19a88444887", "bytes": 2509, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#Tab2", "version": null, "note": "The effect of methylation of every of the 22 CpGs on 5-year OS time", "structure": {"pmcid": "PMC5896072", "section_index": 16, "section_title": "Associations between DFNA5 methylation or expression and 5-year overall survival", "row_count": 24, "column_count": 11}, "table": {"label": "Table 2", "caption": "The effect of methylation of every of the 22 CpGs on 5-year OS time", "rows": [["CpG", "Genomic coordinate (GRCh37)", "All breast adenocarcinomas", "Ductal adenocarcinomas", "Lobular adenocarcinomas"], ["Regression coefficient", "S.E.", "P value", "Regression coefficient", "S.E.", "P value", "Regression coefficient", "S.E.", "P value"], ["CpG17790129", "24738572", "5.1", "1.9", "8.2 × 10−3 *", "6.0", "2.5", "0.019 *", "2.3", "3.8", "0.54"], ["CpG14205998", "24748668", "5.1", "2.1", "0.015 *", "4.9", "2.1", "0.023 *", "13.9", "11.9", "0.24"], ["CpG04317854", "24762562", "1.8", "1.3", "0.16", "2.6", "1.4", "0.064", "− 2.6", "3.5", "0.46"], ["CpG12922093", "24767644", "3.1", "1.2", "0.012 *", "3.8", "1.4", "6.2 × 10−3 *", "− 1.9", "4.2", "0.66"], ["CpG17569154", "24781545", "3.0", "1.2", "0.012 *", "3.6", "1.3", "6.3 × 10−3 *", "− 2.3", "4.4", "0.61"], ["CpG19260663", "24791121", "5.3", "1.9", "4.2 × 10−3 *", "5.7", "2.0", "5.5 × 10−3 *", "7.5", "6.3", "0.23"], ["CpG09333471", "24796355", "2.5", "1.3", "0.059", "1.7", "1.4", "0.22", "11.4", "6.8", "0.093"], ["CpG00473134", "24796494", "0.81", "1.4", "0.57", "0.78", "1.6", "0.62", "4.3", "4.8", "0.37"], ["CpG03995857", "24796553", "− 0.19", "1.0", "0.85", "− 0.75", "1.1", "0.49", "7.4", "5.2", "0.16"], ["CpG07320646", "24796981", "− 0.49", "0.84", "0.55", "− 1.3", "1.0", "0.22", "7.0", "5.3", "0.19"], ["CpG07293520", "24797192", "− 0.17", "1.2", "0.89", "− 1.7", "1.6", "0.29", "9.5", "5.3", "0.072"], ["CpG04770504", "24797363", "− 1.3", "1.2", "0.27", "− 2.4", "1.4", "0.098", "11.7", "8.8", "0.18"], ["CpG24805239", "24797486", "− 0.19", "1.2", "0.87", "− 0.91", "1.3", "0.49", "6.4", "4.5", "0.16"], ["CpG01733570", "24797656", "0.97", "1.0", "0.34", "0.77", "1.0", "0.44", "3.9", "3.9", "0.32"], ["CpG25723149", "24797680", "0.14", "1.0", "0.89", "0.18", "1.0", "0.86", "2.2", "4.1", "0.59"], ["CpG22804000", "24797691", "− 0.092", "1.1", "0.93", "0.087", "1.1", "0.94", "0.51", "3.9", "0.90"], ["CpG07504598", "24797786", "− 0.31", "1.1", "0.77", "− 0.13", "1.1", "0.91", "0.87", "4.2", "0.83"], ["CpG15037663", "24797835", "− 0.21", "1.1", "0.85", "− 0.086", "1.1", "0.94", "3.4", "4.8", "0.48"], ["CpG19706795", "24797839", "0.29", "1.2", "0.80", "0.67", "1.2", "0.58", "0.13", "4.3", "0.98"], ["CpG20764575", "24797884", "− 0.77", "1.1", "0.46", "− 0.60", "1.1", "0.57", "0.84", "5.0", "0.87"], ["CpG06301139", "24798175", "4.2", "2.3", "0.064", "5.0", "2.6", "0.052", "2.9", "5.9", "0.63"], ["CpG26712096", "24798855", "2.4", "1.2", "0.053", "2.7", "1.3", "0.036 *", "3.9", "4.2", "0.35"]], "row_count": 24, "column_count": 11, "numeric_cells": 243, "header_rows": 2, "locator": "section[16]/table-wrap[1]#Tab2"}}], "gaps": ["asset:data:geo:GSE52865 not downloaded", "asset:data:geo:GSE52865 licence not read", "asset:data:geo:GSE60185 not downloaded", "asset:data:geo:GSE60185 licence not read", "asset:data:geo:GSE69914 not downloaded", "asset:data:geo:GSE69914 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "meta_analysis", "specific": "random_effects", "label": "Meta-analysis / evidence synthesis", "dsl_operations": ["random_effects_pool"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["study_level_effect_estimates"], "evidence": {"score": 0.8, "band": "high", "quote": "random effect"}}, {"id": "method-2", "family": "meta_analysis", "specific": "fixed_effects", "label": "Meta-analysis / evidence synthesis", "dsl_operations": [], "missing_operations": ["fixed_effects_pool"], "expressible": false, "parameters": {}, "data_shapes": ["study_level_effect_estimates"], "evidence": {"score": 0.8, "band": "high", "quote": "fixed effects"}}, {"id": "method-3", "family": "regression_modelling", "specific": "mixed_effects", "label": "Regression modelling", "dsl_operations": [], "missing_operations": ["regression_modelling_mixed_effects"], "expressible": false, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.8, "band": "high", "quote": "mixed model"}}, {"id": "method-4", "family": null, "specific": null, "label": "Cox proportional hazard models", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Cox proportional hazard models were fit using the survival package [42], to model 5-year overall survival (OS) time based upon either DFNA5 methylation or DFNA5 expression (microarray or RNA-seq), accounting for age."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "fixed_effects_pool", "expected_value": 0.93, "unit": "auc", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["random_effects_pool"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: random_effects."}, "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": ["GSE52865", "GSE69914", "GSE60185"], "resolved_accessions": ["GSE52865", "GSE69914", "GSE60185"], "statements": ["The datasets analyzed during the current study are available in the following open access repositories:TCGA, https://cancergenome.nih.gov/GEO, https://www.ncbi.nlm.nih.gov/geo/ (GEO accession numbers: GSE52865, GSE69914 and GSE60185)miRTarBase, http://mirtarbase.mbc.nctu.edu.tw/index.php."], "basis": "The paper names GSE52865, GSE69914, GSE60185 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": ["random_effects_pool"], "assets": ["source:pmid:29682089", "data:geo:GSE52865", "asset:table:pmid:29682089:1", "asset:table:pmid:29682089:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE52865"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:18Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 8, "usage": {"prompt_tokens": 98788, "completion_tokens": 6210, "cached_tokens": 1832}}, "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:29682089", "type": "paper", "label": "pmid:29682089"}, {"id": "source:pmid:29682089", "type": "manuscript", "label": "PMID 29682089 full text"}, {"id": "data:geo:GSE52865", "type": "dataset", "label": "GEO GSE52865"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29682089", "type": "paper", "label": "pmid:29682089"}, {"id": "source:pmid:29682089", "type": "manuscript", "label": "PMID 29682089 full text"}, {"id": "data:geo:GSE52865", "type": "dataset", "label": "GEO GSE52865"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29682089", "type": "extraction", "used": ["source:pmid:29682089"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE52865", "type": "accession_resolution", "used": ["data:geo:GSE52865"], "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:29682089", "parent_hash": "sha256:9bd48111e94e4773d75b64c5c17170dd5d1082b3af8e7298d54cc244bee5136f", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE52865 licence not read", "asset:data:geo:GSE52865 not downloaded", "asset:data:geo:GSE60185 licence not read", "asset:data:geo:GSE60185 not downloaded", "asset:data:geo:GSE69914 licence not read", "asset:data:geo:GSE69914 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["denocarcinomas and 56 normal breast samples; RNA-sequencing: 666 breast adenocarcinomas and 71 normal br", "68)Expression–microarray (N = 476)Expression–RNA-seq (N = 666)Number (%)P value (range)Number (%)", "hylation and expression (both microarray and RNA-seq) dataset. The significant p values for the a", "ation, DFNA5 microarray expression, or DFNA5 RNA-seq expression are reportedN.S. not significant"], "order_basis": "paper_text_order:924", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["cal parameterMethylation (N = 668)Expression–microarray (N = 476)Expression–RNA-seq (N = 666)Number", "ted for the methylation and expression (both microarray and RNA-seq) dataset. The significant p valu", "nalysis with either DFNA5 methylation, DFNA5 microarray expression, or DFNA5 RNA-seq expression are", "ither DFNA5 methylation or DFNA5 expression (microarray or RNA-seq), accounting for age. Models with"], "order_basis": "paper_text_order:2977", "id": "assay:2"}, {"role": "analysis", "definition_id": "meta_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["random_effects_pool"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["random effect"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]},"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":"2026-11-04T03:34:21+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}}}