← All .science files
pmid:28167242
Epigenome-Wide DNA Methylation Profiling Identifies Differential Methylation Biomarkers in High-Grade Bladder Cancer.
Ekaterina Olkhov-Mitsel · Andrea J Savio · Ken J Kron · Vaijayanti V Pethe · Thomas Hermanns · Neil E Fleshner · Bas W van Rhijn · Theodorus H van der Kwast · Alexandre R Zlotta · Bharati Bapat
Translational oncology · 2017 doi:10.1016/j.tranon.2017.01.001
Paper
complete
Experiment
partial
Data
partial
Analysis
partial
Execution
absent
Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
paper object · 10 fields
authors array · 10 items
claims array · 3 items
[0] object · 6 fields
evidence array · 1 item
[0] object · 3 fields
[1] object · 6 fields
evidence array · 1 item
[0] object · 3 fields
[2] object · 6 fields
evidence array · 3 items
[0] object · 3 fields
[1] object · 3 fields
gaps array · 0 items
experiment object · 8 fields
steps array · 3 items
[0] object · 13 fields
parameters object · 0 fields
inputs array · 1 item
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[1] object · 13 fields
parameters object · 0 fields
inputs array · 0 items
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
[2] object · 13 fields
parameters object · 0 fields
inputs array · 0 items
outputs array · 1 item
instruments array · 0 items
reagents array · 0 items
materials array · 0 items
instruments array · 0 items
reagents array · 0 items
conditions object · 0 fields
gaps array · 2 items
data object · 3 fields
assets array · 5 items
[0] object · 15 fields
structure object · 4 fields
[1] object · 16 fields
structure object · 5 fields
table object · 8 fields
rows array · 49 items
[0] array · 3 items
[1] array · 3 items
[2] array · 3 items
[3] array · 3 items
[4] array · 3 items
[5] array · 3 items
[6] array · 3 items
[7] array · 3 items
[8] array · 3 items
[9] array · 3 items
[10] array · 3 items
[11] array · 3 items
[12] array · 3 items
[13] array · 3 items
[14] array · 3 items
[15] array · 3 items
[16] array · 3 items
[17] array · 3 items
[18] array · 3 items
[19] array · 3 items
[20] array · 3 items
[21] array · 3 items
[22] array · 3 items
[23] array · 3 items
[24] array · 3 items
[25] array · 3 items
[26] array · 3 items
[27] array · 3 items
[28] array · 3 items
[29] array · 3 items
[30] array · 3 items
[31] array · 3 items
[32] array · 3 items
[33] array · 3 items
[34] array · 3 items
[35] array · 3 items
[36] array · 3 items
[37] array · 3 items
[38] array · 3 items
[39] array · 3 items
[40] array · 3 items
[41] array · 3 items
[42] array · 3 items
[43] array · 3 items
[44] array · 3 items
[45] array · 3 items
[46] array · 3 items
[47] array · 3 items
[48] array · 3 items
[2] object · 16 fields
structure object · 5 fields
table object · 8 fields
rows array · 34 items
[0] array · 4 items
[1] array · 2 items
[2] array · 5 items
[3] array · 5 items
[4] array · 5 items
[5] array · 5 items
[6] array · 5 items
[7] array · 5 items
[8] array · 5 items
[9] array · 5 items
[10] array · 5 items
[11] array · 5 items
[12] array · 5 items
[13] array · 5 items
[14] array · 5 items
[15] array · 5 items
[16] array · 5 items
[17] array · 5 items
[18] array · 5 items
[19] array · 5 items
[20] array · 5 items
[21] array · 5 items
[22] array · 5 items
[23] array · 5 items
[24] array · 5 items
[25] array · 5 items
[26] array · 5 items
[27] array · 5 items
[28] array · 5 items
[29] array · 5 items
[30] array · 5 items
[31] array · 5 items
[32] array · 5 items
[33] array · 5 items
[3] object · 16 fields
structure object · 5 fields
table object · 8 fields
rows array · 60 items
[0] array · 6 items
[1] array · 1 item
[2] array · 6 items
[3] array · 6 items
[4] array · 6 items
[5] array · 1 item
[6] array · 1 item
[7] array · 6 items
[8] array · 6 items
[9] array · 6 items
[10] array · 6 items
[11] array · 1 item
[12] array · 1 item
[13] array · 6 items
[14] array · 6 items
[15] array · 6 items
[16] array · 1 item
[17] array · 1 item
[18] array · 6 items
[19] array · 6 items
[20] array · 6 items
[21] array · 1 item
[22] array · 1 item
[23] array · 6 items
[24] array · 6 items
[25] array · 6 items
[26] array · 1 item
[27] array · 1 item
[28] array · 6 items
[29] array · 6 items
[30] array · 6 items
[31] array · 6 items
[32] array · 6 items
[33] array · 6 items
[34] array · 6 items
[35] array · 1 item
[36] array · 1 item
[37] array · 6 items
[38] array · 6 items
[39] array · 6 items
[40] array · 1 item
[41] array · 1 item
[42] array · 6 items
[43] array · 6 items
[44] array · 6 items
[45] array · 1 item
[46] array · 1 item
[47] array · 6 items
[48] array · 6 items
[49] array · 6 items
[50] array · 1 item
[51] array · 1 item
[52] array · 6 items
[53] array · 6 items
[54] array · 6 items
[55] array · 1 item
[56] array · 1 item
[57] array · 6 items
[58] array · 6 items
[59] array · 6 items
[4] object · 16 fields
structure object · 5 fields
table object · 8 fields
rows array · 28 items
[0] array · 6 items
[1] array · 6 items
[2] array · 6 items
[3] array · 6 items
[4] array · 6 items
[5] array · 6 items
[6] array · 6 items
[7] array · 6 items
[8] array · 6 items
[9] array · 6 items
[10] array · 6 items
[11] array · 6 items
[12] array · 6 items
[13] array · 6 items
[14] array · 6 items
[15] array · 6 items
[16] array · 6 items
[17] array · 6 items
[18] array · 6 items
[19] array · 6 items
[20] array · 6 items
[21] array · 6 items
[22] array · 6 items
[23] array · 6 items
[24] array · 6 items
[25] array · 6 items
[26] array · 6 items
[27] array · 6 items
gaps array · 0 items
analysis object · 4 fields
methods array · 3 items
[0] object · 10 fields
dsl_operations array · 0 items
missing_operations array · 1 item
parameters object · 0 fields
data_shapes array · 1 item
[1] object · 10 fields
dsl_operations array · 0 items
missing_operations array · 1 item
parameters object · 0 fields
data_shapes array · 1 item
[2] object · 10 fields
dsl_operations array · 1 item
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
targets array · 0 items
gaps array · 1 item
capability object · 3 fields
requirements array · 1 item
[0] object · 6 fields
assay_families array · 9 items
gaps array · 0 items
readiness object · 8 fields
axes object · 3 fields
method object · 5 fields
required_operations array · 0 items
missing_operations array · 1 item
capability object · 4 fields
data object · 6 fields
accessions array · 0 items
resolved_accessions array · 0 items
statements array · 1 item
can_run object · 3 fields
dsl_operations array · 0 items
assets array · 5 items
steps array · 0 items
must_build object · 5 fields
dsl_operations array · 1 item
[0] object · 3 fields
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
gaps array · 1 item
review object · 5 fields
machine_critique object · 5 fields
reader object · 5 fields
evidence_check object · 2 fields
usage object · 3 fields
stages array · 1 item
[0] object · 4 fields
gaps array · 3 items
provenance object · 7 fields
entities array · 3 items
activities array · 3 items
[0] object · 4 fields
used array · 3 items
[0] object · 3 fields
[1] object · 3 fields
[2] object · 3 fields
[1] object · 4 fields
agents array · 2 items
lineage object · 4 fields
gaps array · 7 items
assays array · 2 items
[0] object · 11 fields
required_operations array · 0 items
source_hashes object · 1 field
evidence array · 1 item
[1] object · 11 fields
required_operations array · 0 items
source_hashes object · 1 field
evidence array · 1 item
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:28167242", "kind": "science-record", "revision": 7, "content_hash": "sha256:8ccc5adbda0535cccbbf5e4d86c193eb8de3e1c1d213abb73f043ea195d201ce", "created_at": "2026-11-01T15:40:22Z", "updated_at": "2026-11-01T21:59:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Epigenome-Wide DNA Methylation Profiling Identifies Differential Methylation Biomarkers in High-Grade Bladder Cancer.", "doi": "10.1016/j.tranon.2017.01.001", "pmid": "28167242", "authors": ["Ekaterina Olkhov-Mitsel", "Andrea J Savio", "Ken J Kron", "Vaijayanti V Pethe", "Thomas Hermanns", "Neil E Fleshner", "Bas W van Rhijn", "Theodorus H van der Kwast", "Alexandre R Zlotta", "Bharati Bapat"], "journal": "Translational oncology", "year": 2017, "abstract": "Epigenetic changes, including CpG island hypermethylation, occur frequently in bladder cancer (BC) and may be exploited for BC detection and distinction between high-grade (HG) and low-grade (LG) disease. Genome-wide methylation analysis was performed using Agilent Human CpG Island Microarrays to determine epigenetic differences between LG and HG cases. Pathway enrichment analysis and functional annotation determined that the most frequently methylated pathways in HG BC were enriched for anterior/posterior pattern specification, embryonic skeletal system development, neuron fate commitment, DNA binding, and transcription factor activity. We identified 990 probes comprising a 32-gene panel that completely distinguished LG from HG based on methylation. Selected genes from this panel, EOMES, GP5, PAX6, TCF4, and ZSCAN12, were selected for quantitative polymerase chain reaction-based validation by MethyLight in an independent series (n=84) of normal bladder samples and LG and HG cases. GP5 and ZSCAN12, two novel methylated genes in BC, were significantly hypermethylated in HG versus LG BC (P≤.03). We validated our data in a second independent cohort of LG and HG BC cases (n=42) from The Cancer Genome Atlas (TCGA). Probes representing our 32-gene panel were significantly differentially methylated in LG versus HG tumors (P≤.04). These results indicate the ability to distinguish normal tissue from cancer, as well as LG from HG, based on methylation and reveal important pathways dysregulated in HG BC. Our findings were corroborated using publicly available data sets from TCGA. Ultimately, the creation of a methylation panel, including GP5 and ZSCAN12, able to distinguish between disease phenotypes will improve disease management and patient outcomes.", "claims": [{"id": "claim-method", "statement": "Comparison of median PMR values between LG, HG, and normal samples and other clinicopathological variables was performed using the Mann-Whitney U test or Kruskal-Wallis test, where appropriate.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28167242", "locator": "sections[12] \"Statistical Analysis\" paragraph 2", "quote": "Comparison of median PMR values between LG, HG, and normal samples and other clinicopathological variables was performed using the Mann-Whitney U test or Kruskal-Wallis test, where appropriate."}], "state": "complete"}, {"id": "claim-data-access", "statement": "For these 42 total selected cases, level 3 methylation data from Illumina Infinium HumanMethylation450 BeadChip arrays were downloaded from TCGA in March 2016. Methylation data were also downloaded for all 21 benign bladder tissue samples available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28167242", "locator": "sections[11] \"The Cancer Genome Atlas (TCGA) Data Set\" paragraph 2", "quote": "For these 42 total selected cases, level 3 methylation data from Illumina Infinium HumanMethylation450 BeadChip arrays were downloaded from TCGA in March 2016. Methylation data were also downloaded for all 21 benign bladder tissue samples available."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Genome-wide methylation analysis identified a 32-gene methylation panel that completely distinguished low-grade from high-grade bladder cancer and was validated with MethyLight and TCGA data.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28167242", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified 990 probes comprising a 32-gene panel that completely distinguished LG from HG based on methylation."}, {"asset": "source:pmid:28167242", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Selected genes from this panel, EOMES, GP5, PAX6, TCF4, and ZSCAN12, were selected for quantitative polymerase chain reaction–based validation by MethyLight in an independent series (n = 84) of normal bladder samples and LG and HG cases."}, {"asset": "source:pmid:28167242", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We validated our data in a second independent cohort of LG and HG BC cases (n = 42) from The Cancer Genome Atlas (TCGA)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Genome-wide methylation analysis identified a 32-gene methylation panel that completely distinguished low-grade from high-grade bladder cancer and was validated with MethyLight and TCGA data.", "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:28167242"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_mann_whitney", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney", "step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:28167242", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.tranon.2017.01.001", "sha256": "sha256:50265a52677d6e9ff9816a5743e3e50bdf7e1a8d6e767efe54941d2d37475daf", "bytes": 49077, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.tranon.2017.01.001", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5293735", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:28167242:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:87e06c45942931dc922b93972ebbd1731c511449c950525a30f5dcd7a7ab9bcb", "bytes": 2043, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#t0005", "version": null, "note": "Clinicopathological Variables of LG and HG BC Patients of Cohort Used for MethyLight Gene-Specific Methylation Analysis", "structure": {"pmcid": "PMC5293735", "section_index": 3, "section_title": "Patients and Pathology", "row_count": 49, "column_count": 3}, "table": {"label": "Table 1", "caption": "Clinicopathological Variables of LG and HG BC Patients of Cohort Used for MethyLight Gene-Specific Methylation Analysis", "rows": [["Clinicopathological Variable", "LG, N (%)", "HG, N (%)"], ["Gender", "", ""], ["Male", "27 (67.5)", "27 (67.5)"], ["Female", "13 (32.5)", "13 (32.5)"], ["Age group", "", ""], ["< 50", "2 (5.0)", "4 (10.0)"], ["50-59", "9 (22.5)", "8 (20.0)"], ["60-69", "16 (40.0)", "15 (37.5)"], ["70-79", "12 (30.0)", "12 (30.0)"], ["80-89", "1 (2.5)", "1 (2.5)"], ["Grade", "", ""], ["LG", "40 (100.0)", "0 (0.0)"], ["HG", "0 (0.0)", "40 (100.0)"], ["Pathological stage", "", ""], ["Ta", "21 (52.5)", "0 (0.0)"], ["T1", "18 (45.0)", "34 (85.0)"], ["T2a", "0 (0.0)", "1 (2.5)"], ["T2b", "1 (2.5)", "0 (0.0)"], ["T3a", "0 (0.0)", "4 (10.0)"], ["T3b", "0 (0.0)", "1 (2.5)"], ["Surgery", "", ""], ["Transurethral resection of bladder tumor", "16 (40.0)", "33 (82.5)"], ["Radical cystectomy", "7 (17.5)", "7 (17.5)"], ["No data", "17 (42.5)", "0 (0.0)"], ["Recurrence", "", ""], ["No recurrence", "4 (10.0)", "14 (35.0)"], ["Recurrence", "12 (30.0)", "18 (45.0)"], ["No data", "24 (60.0)", "8 (20.0)"], ["FGFR3 mutation", "", ""], ["Wild type", "10 (25.0)", "30 (75.0)"], ["Mutation", "13 (32.5)", "9 (22.5)"], ["No data", "17 (42.5)", "1 (2.5)"], ["FGFR3 expression", "", ""], ["Not expressed", "6 (15.0)", "18 (45.0)"], ["Expressed", "17 (42.5)", "21 (52.5)"], ["No data", "17 (42.5)", "1 (2.5)"], ["P53 expression", "", ""], ["Not expressed", "22 (55.0)", "18 (45.0)"], ["Expressed", "1 (2.5)", "22 (55.0)"], ["No data", "17 (42.5)", "0 (0.0)"], ["P27 expression", "", ""], ["Not expressed", "13 (32.5)", "21 (52.5)"], ["Expressed", "10 (25.0)", "19 (47.5)"], ["No data", "17 (42.5)", "0 (0.0)"], ["EOMES median PMR (range)", "30.2 (0.0-100.0)", "41.8 (1.8-100.0)"], ["GP5 median PMR (range)", "0.0 (0.0-53.7)", "1.6 (0.0-87.6)"], ["PAX6 median PMR (range)", "19.0 (0.0-69.4)", "22.4 (0.0-100.0)"], ["TCF4 median PMR (range)", "0.0 (0.0-37.5)", "0.2 (0.0-37.9)"], ["ZSCAN12 median PMR (range)", "0.0 (0.0-73.56)", "10.9 (0.0-74.9)"]], "row_count": 49, "column_count": 3, "numeric_cells": 84, "header_rows": 1, "locator": "section[3]/table-wrap[1]#t0005"}}, {"id": "asset:table:pmid:28167242:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7600bf94004cd243a521f0a51c4567ec2c1acf926f76dae87e938b68699d9fc2", "bytes": 2743, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#t0010", "version": null, "note": "List of the 19 Most Significantly Hypermethylated and 13 Hypomethylated Genes between LG and HG BC, Comprising a 32-Gene Panel", "structure": {"pmcid": "PMC5293735", "section_index": 14, "section_title": "Genome-Wide Methylation in LG and HG BC", "row_count": 34, "column_count": 5}, "table": {"label": "Table 2", "caption": "List of the 19 Most Significantly Hypermethylated and 13 Hypomethylated Genes between LG and HG BC, Comprising a 32-Gene Panel", "rows": [["Gene Name (Abbreviation)", "Number of Probes", "Fold Change", "P Value"], ["LPE", "Limma"], ["Von Willebrand factor C domain containing 2 (UNQ739)", "1", "66.7", "3.51 × 10−6", "2.16 × 10−5"], ["Uncharacterized LOC389064 (FLJ46347)", "2", "41.3", ".0006", ".0332"], ["Eomesodermin (EOMES)", "3", "36.5", ".0104", ".0016"], ["Glycoprotein V (platelet) (GP5)", "4", "36.3", ".0108", ".0006"], ["Solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2)", "2", "36.1", ".0116", ".0002"], ["Glial cell–derived neurotrophic factor (GDNF)", "4", "33.6", ".0033", ".0136"], ["Short stature homeobox (SHOX)", "3", "32.6", ".0156", ".0238"], ["Olfactory receptor, family 10, subfamily AD, member 1 (OR10AD1)", "4", "31.8", ".0013", ".0005"], ["Glutamate receptor, ionotropic, kainate 1 (GRIK1)", "1", "29.4", ".0017", ".0035"], ["Zinc finger protein 418 (ZNF418)", "1", "28.8", "1.13 × 10−5", ".0006"], ["Forkhead box E1 (thyroid transcription factor 2) (FOXE1)", "1", "28.3", ".0005", ".0001"], ["Zinc finger and SCAN domain containing 12 (ZSCAN12/ZNF96)", "6", "26.8", ".0096", ".0062"], ["Homeobox D9 (HOXD9)", "1", "24.4", "7.63 × 10−6", ".0017"], ["Phosphatidylinositol-3,4,5-trisphosphate–dependent Rac exchange factor 1 (PREX1)", "1", "23.4", ".0004", ".0311"], ["Engulfment adaptor PTB domain containing 1 (GULP1)", "6", "23.1", ".0025", ".0069"], ["Myosin binding protein C, slow type (MYBPC1)", "1", "23.0", ".0009", ".0071"], ["Motor neuron and pancreas homeobox 1 (HLXB9)", "1", "22.3", "4.02 × 10−5", ".0003"], ["Glutamate receptor, ionotropic, AMPA 2 (GRIA2)", "2", "22.0", ".0002", ".0003"], ["Paired box 6 (PAX6)", "8", "21.8", ".0063", ".004"], ["small nucleolar RNA, H/ACA box 70 (U70)", "1", "−8.9", ".033", ".011"], ["Protease, serine, 21 (PRSS21)", "1", "−7.8", ".043", ".008"], ["Carbonic anhydrase XIII (CA13)", "1", "−7.7", ".021", ".019"], ["Translocase of outer mitochondrial membrane 40 homolog (TOMM40)", "1", "−6.9", ".029", ".002"], ["Phosphorylase kinase, alpha 1 (PHKA1)", "1", "−6.9", ".047", ".004"], ["DOK2-XPO7", "1", "−6.4", ".043", ".012"], ["Kruppel-like factor 11 (KLF11)", "1", "−6.3", ".018", ".018"], ["BCL2-associated transcription factor 1 (BCLAF1)", "1", "−6.2", ".027", ".024"], ["Single-minded homolog 1 (Drosophila) (SIM1)", "2", "−5.0", ".045", ".006"], ["FLJ43870", "1", "−4.7", ".043", ".028"], ["BMP and activin membrane-bound inhibitor homolog (Xenopus laevis) (BAMBI)", "1", "−4.4", ".044", ".039"], ["Ribosomal protein L31 (RPL31)", "1", "−4.3", ".045", ".011"], ["Homeobox A9 (HOXA9)", "1", "−3.8", ".043", ".002"]], "row_count": 34, "column_count": 5, "numeric_cells": 151, "header_rows": 2, "locator": "section[14]/table-wrap[1]#t0010"}}, {"id": "asset:table:pmid:28167242:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:47b57199eb2c53c2d51aed27c2fc061f4bcd72d741a0eba1b2cd901a2d8f658c", "bytes": 2252, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#t0015", "version": null, "note": "Associations between Methylation of Five Genes and Clinicopathological Variables in BC Patients", "structure": {"pmcid": "PMC5293735", "section_index": 17, "section_title": "Gene-Specific Methylation Analysis", "row_count": 60, "column_count": 6}, "table": {"label": "Table 3", "caption": "Associations between Methylation of Five Genes and Clinicopathological Variables in BC Patients", "rows": [["Clinicopathological Variable", "EOMES PMR", "GP5 PMR", "PAX6 PMR", "TCF4 PMR", "ZSCAN12 PMR"], ["Normal vs cancer"], ["Normal", "0.0", "0.0", "3.9", "0.0", "0.9"], ["Cancer", "31.8", "0.0", "20.2", "0.1", "3.1"], ["P value", "1.2 × 10−4", ".22", ".06", ".19", ".29"], [""], ["Normal vs LG vs HG"], ["Normal", "0.0", "0.0", "3.9", "0.0", "0.9"], ["LG", "30.2", "0.0", "19.0", "0.01", "0.0"], ["HG", "41.8", "1.6", "22.4", "0.2", "10.9"], ["P value", ".001", ".008", ".11", ".32", ".04"], [""], ["LG vs HG"], ["LG", "30.2", "0.0", "19.0", "0.01", "0.0"], ["HG", "41.8", "1.6", "22.4", "0.2", "10.9"], ["P value", ".05", ".006", ".34", ".53", ".03"], [""], ["Normal vs LG"], ["Normal", "0.0", "0.0", "3.9", "0.0", "0.9"], ["LG", "30.2", "0.0", "19.0", "0.01", "0.0"], ["P value", ".002", ".43", ".07", ".23", ".66"], [""], ["Normal vs HG"], ["Normal", "0.0", "0.0", "3.9", "0.0", "0.9"], ["HG", "41.8", "1.6", "22.4", "0.2", "10.9"], ["P value", "1.8 × 10−5", ".11", ".06", ".19", ".10"], [""], ["Stage"], ["Ta", "9.7", "0.0", "9.3", "0.01", "0.0"], ["T1", "46.1", "0.0", "26.7", "0.2", "10.9"], ["T2a", "31.0", "16.4", "16.0", "0.0", "0.0"], ["T2b", "15.8", "5.8", "7.4", "4.6", "0.8"], ["T3a", "18.4", "1.7", "3.4", "0.6", "3.4"], ["T3b", "55.7", "62.7", "1.0", "0.0", "12.4"], ["P value", ".047", ".51", "4.6 × 10−4", ".03", ".001"], [""], ["Recurrence"], ["No recurrence", "43.5", "0.0", "22.8", "0.04", "0.3"], ["Recurrence", "46.1", "2.5", "30.7", "0.7", "11.7"], ["P value", ".80", ".17", ".17", ".64", ".23"], [""], ["P53 expression"], ["Not expressed", "21.6", "0.0", "12.9", "0.01", "0.3"], ["Expressed", "41.4", "0.0", "26.3", "0.01", "1.1"], ["P value", ".09", ".02", ".31", ".35", ".39"], [""], ["P27 expression"], ["Not expressed", "31.0", "0.0", "23.9", "0.0", "4.6"], ["Expressed", "22.8", "0.0", "12.9", "0.02", "0.0"], ["P value", ".91", ".001", ".80", ".88", ".36"], [""], ["FGFR3 mutation"], ["Wild-type", "28.5", "0.0", "16.6", "0.0", "2.1"], ["Mutated", "36.4", "0.0", "23.9", "0.2", "0.0"], ["P value", ".09", ".11", ".81", ".37", ".005"], [""], ["FGFR3 expression"], ["Not expressed", "30.0", "0.0", "14.6", "0.02", "0.5"], ["Expressed", "27.9", "0.0", "23.8", "0.01", "0.3"], ["P value", ".30", ".002", ".29", ".34", ".005"]], "row_count": 60, "column_count": 6, "numeric_cells": 193, "header_rows": 1, "locator": "section[17]/table-wrap[1]#t0015"}}, {"id": "asset:table:pmid:28167242:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:176fc5f881518a0ec48a313c0f2357afae0a2503c947d29dcc2092fd7dae6e20", "bytes": 1572, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#t0020", "version": null, "note": "Associations between Methylation of a Five-Gene Panel and Grade in BC Patients from TCGA", "structure": {"pmcid": "PMC5293735", "section_index": 18, "section_title": "Gene-Specific Validation in TCGA Data Set", "row_count": 28, "column_count": 6}, "table": {"label": "Table 4", "caption": "Associations between Methylation of a Five-Gene Panel and Grade in BC Patients from TCGA", "rows": [["Gene", "EOMES", "GP5", "PAX6", "TCF4", "ZSCAN12"], ["Probe ID", "cg21473142", "cg18780769", "cg24701575", "cg23482397", "cg20271532"], ["Benign vs cancer", "", "", "", "", ""], ["Benign", "0.261", "0.137", "0.137", "0.022", "0.072"], ["Cancer", "0.606", "0.129", "0.281", "0.028", "0.098"], ["P value", ".003", ".94", ".02", "1.9 × 10−4", ".31"], ["Benign vs LG vs HG", "", "", "", "", ""], ["Benign", "0.261", "0.137", "0.137", "0.022", "0.072"], ["LG", "0.314", "0.092", "0.156", "0.026", "0.056"], ["HG", "0.753", "0.232", "0.465", "0.046", "0.225"], ["P value", "2.7 × 10−5", "2.9 × 10−4", "1.3 × 10−4", "1.7 × 10−4", ".02"], ["LG vs HG", "", "", "", "", ""], ["LG", "0.314", "0.092", "0.156", "0.046", "0.225"], ["HG", "0.753", "0.232", "0.565", "0.026", "0.056"], ["P value", ".003", ".001", ".001", ".04", ".02"], ["Benign vs LG", "", "", "", "", ""], ["Benign", "0.261", "0.137", "0.137", "0.022", "0.072"], ["LG", "0.314", "0.092", "0.156", "0.026", "0.056"], ["P value", ".77", ".009", ".97", ".01", ".46"], ["Benign vs HG", "", "", "", "", ""], ["Benign", "0.246", "0.137", "0.137", "0.022", "0.072"], ["HG", "0.753", "0.232", "0.565", "0.046", "0.225"], ["P value", "2.3 × 10−6", ".01", "5.5 × 10−5", "9.3 × 10−5", ".01"], ["Stage", "", "", "", "", ""], ["T2", "0.321", "0.125", "0.226", "0.027", "0.079"], ["T3", "0.671", "0.098", "0.280", "0.046", "0.070"], ["T4", "0.732", "0.195", "0.347", "0.027", "0.429"], ["P value", ".12", ".39", ".77", ".59", ".44"]], "row_count": 28, "column_count": 6, "numeric_cells": 106, "header_rows": 1, "locator": "section[18]/table-wrap[1]#t0020"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Comparison of median PMR values between LG, HG, and normal samples and other clinicopathological variables was performed using the Mann-Whitney U test or Kruskal-Wallis test, where appropriate."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pathway enrichment"}}], "targets": [], "gaps": ["method.group_comparison_mann_whitney"]}, "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": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: mann_whitney."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["For these 42 total selected cases, level 3 methylation data from Illumina Infinium HumanMethylation450 BeadChip arrays were downloaded from TCGA in March 2016. Methylation data were also downloaded for all 21 benign bladder tissue samples available."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:28167242", "asset:table:pmid:28167242:1", "asset:table:pmid:28167242:2", "asset:table:pmid:28167242:3", "asset:table:pmid:28167242:4"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_mann_whitney", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:30:25Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 104789, "completion_tokens": 3624, "cached_tokens": 2107}}, "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:28167242", "type": "paper", "label": "pmid:28167242"}, {"id": "source:pmid:28167242", "type": "manuscript", "label": "PMID 28167242 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:28167242", "type": "paper", "label": "pmid:28167242"}, {"id": "source:pmid:28167242", "type": "manuscript", "label": "PMID 28167242 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-28167242", "type": "extraction", "used": ["source:pmid:28167242"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:28167242", "parent_hash": "sha256:edc084713cad56ee94f49eaf5ada974ed7bf87ec160a106f389c5987aafc8c88", "fork_of": null, "generation": 6}, "gaps": ["execution.not_run", "method.group_comparison_mann_whitney", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent", "step:run_analysis blocked on method:group_comparison_mann_whitney"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["by a quantitative polymerase chain reaction (qPCR)–based methylation detection assay, MethyLig"], "order_basis": "paper_text_order:2311", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Comparison of median PMR values between LG, HG, and normal samples and other clinicopathological variables was performed using the Mann-Whitney U test or Kruskal-Wallis test, where appropriate."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}