{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27716369", "kind": "science-record", "revision": 6, "content_hash": "sha256:87405e2323f281a6ff7b41f90f56cd6eec39ca96509b1a4cfef82f55dfa454da", "created_at": "2026-11-01T15:40:20Z", "updated_at": "2026-11-01T21:20:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium.", "doi": "10.1186/s13058-016-0758-5", "pmid": "27716369", "authors": ["Taru A Muranen", "Carl Blomqvist", "Thilo Dörk", "Anna Jakubowska", "Päivi Heikkilä", "Rainer Fagerholm", "Dario Greco", "Kristiina Aittomäki", "Stig E Bojesen", "Mitul Shah", "Alison M Dunning", "Valerie Rhenius", "Per Hall", "Kamila Czene", "Judith S Brand", "Hatef Darabi", "Jenny Chang-Claude", "Anja Rudolph", "Børge G Nordestgaard", "Fergus J Couch", "Steven N Hart", "Jonine Figueroa", "Montserrat García-Closas", "Peter A Fasching", "Matthias W Beckmann", "Jingmei Li", "Jianjun Liu", "Irene L Andrulis", "Robert Winqvist", "Katri Pylkäs", "Arto Mannermaa", "Vesa Kataja", "Annika Lindblom", "Sara Margolin", "Jan Lubinski", "Natalia Dubrowinskaja", "Manjeet K Bolla", "Joe Dennis", "Kyriaki Michailidou", "Qin Wang", "Douglas F Easton", "Paul D P Pharoah", "Marjanka K Schmidt", "Heli Nevanlinna"], "journal": "Breast cancer research : BCR", "year": 2016, "abstract": "BACKGROUND: P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers.\nMETHODS: We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature.\nRESULTS: P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly enriched among genes, whose expression differed between p.I157T and non-carrier tumors.\nCONCLUSIONS: Our analyses suggest that there are fundamental differences in breast tumors of CHEK2:p.I157T and c.1100delC carriers. The poor prognosis associated with c.1100delC cannot be generalized to other CHEK2 mutations.", "claims": [{"id": "claim-method", "statement": "Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27716369", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The dataset supporting the conclusions of this article is available in the Gene Expression Omnibus (GEO) repository, GEO: GSE24450, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24450.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27716369", "locator": "sections[19] \"ack\" paragraph 1", "quote": "The dataset supporting the conclusions of this article is available in the Gene Expression Omnibus (GEO) repository, GEO: GSE24450, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24450."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Using Cox proportional hazards regression on survival and genotype data from 26,801 European female breast cancer patients recruited through 15 Breast Cancer Association Consortium studies, the paper found that p.I157T was not associated with increased risk of early death, breast cancer-associated death, or distant metastasis relapse, and that prognosis differed significantly between p.I157T and c.1100delC carriers.", "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:27716369"], "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": "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:27716369", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13058-016-0758-5", "sha256": "sha256:acf94cb8cecc4529c3b29d95e9abc7ec631323c32d39b0835bc9a6cc7d05a1a0", "bytes": 49197, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13058-016-0758-5", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5048645", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:27716369:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7f594784af71afcf97b98e76cb123a03e26ae57f139e5bb09931605456fe970b", "bytes": 3839, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#Tab1", "version": null, "note": "Tumor characteristics of the BCAC study subjects", "structure": {"pmcid": "PMC5048645", "section_index": 3, "section_title": "Study subjects for survival and pathology analyses", "row_count": 96, "column_count": 8}, "table": {"label": "Table 1", "caption": "Tumor characteristics of the BCAC study subjects", "rows": [["", "Non-carriers", "p.I157T carriers", "c.1100delC carriers", "p value (I157T/nc)", "p value (I157T/1100delC)", "p value (1100delC/nc)"], ["ER", "Negative", "4595", "85", "26", "0.00046", "0.61", "0.0015"], ["20.2 %", "15.5 %", "11.2 %"], ["Positive", "18,179", "462", "207"], ["79.8 %", "84.5 %", "88.8 %"], ["Missing", "3166", "43", "38", "", "", ""], ["12.2 %", "7.3 %", "14.0 %"], ["PR", "Negative", "6397", "147", "44", "0.0034", "0.90", "0.0045"], ["32.7 %", "28.5 %", "23.3 %"], ["Positive", "13,173", "368", "145"], ["67.3 %", "71.5 %", "76.7 %"], ["Missing", "6370", "75", "82", "", "", ""], ["24.6 %", "12.7 %", "30.3 %"], ["Her2", "Negative", "8220", "231", "95", "0.68", "0.10", "0.24"], ["84.7 %", "83.7 %", "81.9 %"], ["Positive", "1483", "45", "21"], ["15.3 %", "16.3 %", "18.1 %"], ["Missing", "16,237", "314", "155", "", "", ""], ["62.6 %", "53.2 %", "57.2 %"], ["EGFR", "Negative", "3841", "122", "62", "0.21", "0.26", "0.034"], ["89.6 %", "90.4 %", "96.9 %"], ["Positive", "448", "13", "2"], ["10.4 %", "9.6 %", "3.1 %"], ["Missing", "21,651", "455", "207", "", "", ""], ["83.5 %", "77.1 %", "76.4 %"], ["CK5/6", "Negative", "4734", "143", "80", "0.30", "0.29", "0.19"], ["87.9 %", "88.3 %", "92.0 %"], ["Positive", "652", "19", "7"], ["12.1 %", "11.7 %", "8.0 %"], ["Missing", "20,554", "428", "184", "", "", ""], ["79.2 %", "72.5 %", "67.9 %"], ["TP53", "Negative", "3755", "144", "88", "0.00048", "0.21", "0.16"], ["81.6 %", "90.6 %", "86.3 %"], ["Positive", "847", "15", "14"], ["18.4 %", "9.4 %", "13.7 %"], ["Missing", "21,338", "431", "169", "", "", ""], ["82.3 %", "73.1 %", "62.4 %"], ["Tumor size (ordinal)", "<20 mm", "14,949", "340", "149", "0.29", "0.33", "0.83"], ["65.6 %", "65.6 %", "62.6 %"], ["20–50 mm", "6953", "162", "82"], ["30.5 %", "31.3 %", "34.5 %"], [">50 mm", "876", "16", "7"], ["3.8 %", "3.1 %", "2.9 %"], ["Missing", "3162", "72", "33", "", "", ""], ["12.2 %", "12.2 %", "12.2 %"], ["Lymph node status", "Negative", "13,144", "320", "125", "0.94", "0.91", "0.64"], ["62.0 %", "60.4 %", "57.6 %"], ["Positive", "8070", "210", "92"], ["38.0 %", "39.6 %", "42.4 %"], ["Missing", "4726", "60", "54", "", "", ""], ["18.2 %", "10.2 %", "19.9 %"], ["Grade (ordinal)", "1", "4916", "132", "38", "0.00023", "0.0030", "0.38"], ["22.5 %", "26.7 %", "17.4 %"], ["2", "10,817", "266", "127"], ["49.6 %", "53.7 %", "58.0 %"], ["3", "6089", "97", "54", "", "", ""], ["27.9 %", "19.6 %", "24.7 %"], ["Missing", "4118", "95", "52", "", "", ""], ["15.9 %", "16.1 %", "19.2 %"], ["Histological type", "Ductal", "14,133", "273", "193", "0.0044*", "0.0010#", "0.67#"], ["72.7 %", "60.0 %", "76.9 %"], ["Lobular", "2966", "100", "36"], ["15.3 %", "22.0 %", "14.3 %"], ["Mixed (ductal and lobular)", "455", "26", "4"], ["2.5 %", "6.0 %", "1.7 %"], ["Tubular", "271", "17", "2"], ["1.5 %", "4.0 %", "0.7 %"], ["Medullary", "177", "4", "3"], ["1.0 %", "0.9 %", "1.7 %"], ["Mucinous", "213", "9", "3"], ["1.2 %", "2.1 %", "1.4 %"], ["Papillary", "55", "1", "1"], ["0.3 %", "0.2 %", "1.8 %"], ["Missing†", "7670", "160", "29", "", "", ""], ["29.6 %", "27.1 %", "10.7 %"], ["Subtype‡", "LumA (ER+, PR+, Her2-)", "5415", "164", "72", "0.00089", "0.46", "0.0087"], ["58.9 %", "63.6 %", "65.5 %"], ["LumB (ER+, PR-, Her2- or ER+, Her2+)", "1939", "62", "30"], ["21.1 %", "24.0 %", "27.3 %"], ["Basal (ER-, PR-, Her2-)", "1306", "16", "4"], ["14.2 %", "6.2 %", "3.6 %"], ["Her2-positive (ER-, PR-, Her2+)", "536", "16", "4"], ["5.8 %", "6.2 %", "3.6 %"], ["Missing", "16,744", "332", "161", "", "", ""], ["64.5 %", "56.3 %", "59.4 %"], ["AGE cat (ordinal)", "50 or younger", "6932", "162", "101", "0.99", "0.0037", "0.0029"], ["27.0 %", "27.8 %", "37.3 %"], ["Older than 50 and not more than 70", "16,083", "344", "151"], ["62.6 %", "59.0 %", "55.7 %"], ["Older than 70", "2674", "77", "19"], ["10.4 %", "13.2 %", "7.0 %"], ["Missing", "251", "7", "0", "", "", ""], ["1.0 %", "1.2 %", "0.0 %"], ["AGE", "Mean", "57.1", "57.9", "54.3", "0.41", "0.028", "0.024"], ["St.dev.", "10.8", "11.1", "11.0"], ["Total", "", "25,940", "590", "271", "", "", ""]], "row_count": 96, "column_count": 8, "numeric_cells": 340, "header_rows": 1, "locator": "section[3]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:27716369:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7e87bf537ac23896155726d0a5098f82e6bdb92e425eb6ee6257f33a555d926f", "bytes": 678, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#Tab2", "version": null, "note": "Phenotypic classification of breast tumors from ten carriers of p.I157T", "structure": {"pmcid": "PMC5048645", "section_index": 11, "section_title": "Breast cancer subtypes", "row_count": 11, "column_count": 4}, "table": {"label": "Table 2", "caption": "Phenotypic classification of breast tumors from ten carriers of p.I157T", "rows": [["", "Intrinsic subtype PAM50", "IHC subtype St Gallen 2013 criteria", "Histological type"], ["HEL_045", "Normal", "LumA", "Lobular"], ["HEL_055", "LumB", "LumB", "Ductal"], ["HEL_086", "LumA", "LumA", "Lobular"], ["HEL_126", "LumA", "Basal", "Ductal"], ["HEL_128", "LumA", "LumB", "Ductal"], ["HEL_131", "Basal", "Her2pos", "In situ"], ["HEL_144", "Normal", "LumB", "Lobular"], ["HEL_150", "Basal", "LumB", "Ductal"], ["HEL_163", "LumB", "LumB", "Ductal"], ["HEL_174", "Normal", "LumA", "Lobular"]], "row_count": 11, "column_count": 4, "numeric_cells": 12, "header_rows": 1, "locator": "section[11]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:27716369:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:52e303b4aebb6da6804436fa908d7fded35cbffc0fa4dc5cb7165d31810a51c6", "bytes": 2904, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab3", "version": null, "note": "Risk of death or disease recurrence associated with CHEK2:p.I157T", "structure": {"pmcid": "PMC5048645", "section_index": 12, "section_title": "Patient survival", "row_count": 36, "column_count": 7}, "table": {"label": "Table 3", "caption": "Risk of death or disease recurrence associated with CHEK2:p.I157T", "rows": [["(a) All breast cancer patients", "Univariate analysis", "Adjusted analysis"], ["I157T/nc", "I157T/1100delC", "1100delc/nc", "I157T/nc", "I157T/1100delC", "1100delC/nc"], ["Early death", "0.85 [0.68 - 1.07]", "0.74 [0.50 - 1.09]", "1.28 [1.00 - 1.64]", "0.80 [0.60 - 1.07]", "0.51 [0.29 - 0.90]", "1.32 [0.94 - 1.86]"], ["0.16", "0.12", "0.054", "0.13", "0.0190", "0.11"], ["Breast cancer-specific death", "0.85 [0.60 - 1.20]", "0.64 [0.37 - 1.12]", "1.44 [1.04 - 2.00]", "0.93 [0.62 - 1.40]", "0.46 [0.21 - 1.03]", "1.25 [0.78 - 2.00]"], ["0.36", "0.12", "0.030", "0.73", "0.058", "0.36"], ["Distant metastasis relapse", "1.04 [0.79 - 1.37]", "0.66 [0.38 - 1.14]", "1.38 [0.90 - 2.11]", "1.05 [0.75 - 1.47]", "0.62 [0.31 - 1.23]", "1.37 [0.83 - 2.26]"], ["0.79", "0.13", "0.14", "0.76", "0.17", "0.22"], ["Locoregional relapse", "1.43 [0.92 - 2.23]", "0.81 [0.58 - 1.13]", "2.07 [1.16 - 3.69]", "1.62 [0.99 - 2.66]", "0.91 [0.33 - 2.52]", "1.26 [0.59 - 2.70]"], ["0.11", "0.21", "0.014", "0.056", "0.85", "0.55"], ["Second breast cancer", "1.54 [0.85 - 2.78]", "0.69 [0.47 - 1.03]", "2.88 [1.68 - 4.98]", "2.03 [1.05 - 3.92]", "0.69 [0.42 - 1.13]", "3.62 [1.82 - 7.21]"], ["0.15", "0.070", "0.00015", "0.035", "0.14", "0.00026"], ["(b) Patients with ER+ breast cancer", "Univariate analysis", "Adjusted analysis"], ["I157T/nc", "I157T/1100delC", "1100delc/nc", "I157T/nc", "I157T/1100delC", "1100delC/nc"], ["Early death", "0.81 [0.61 - 1.07]", "0.62 [0.39 - 0.99]", "1.32 [0.98 - 1.78]", "0.77 [0.55 - 1.07]", "0.46 [0.25 - 0.85]", "1.52 [1.06 - 2.17]"], ["0.14", "0.044", "0.067", "0.12", "0.013", "0.022"], ["Breast cancer-specific death", "0.80 [0.51 - 1.23]", "0.47 [0.23 - 0.96]", "1.46 [0.96 - 2.22]", "0.80 [0.49 - 1.32]", "0.33 [0.13 - 0.84]", "1.50 [0.92 - 2.45]"], ["0.30", "0.038", "0.074", "0.39", "0.019", "0.10"], ["Distant metastasis relapse", "1.00 [0.71 - 1.40]", "0.55 [0.29 - 1.02]", "1.58 [0.99 - 2.54]", "1.03 [0.70 - 1.51]", "0.56 [0.26 -1.19]", "1.61 [0.94 - 2.77]"], ["0.98", "0.057", "0.056", "0.88", "0.13", "0.083"], ["Locoregional relapse", "1.46 [0.86 - 2.47]", "0.77 [0.52 - 1.14]", "2.33 [1.19 - 4.57]", "1.58 [0.90 - 2.79]", "0.93 [0.29 - 2.98]", "1.08 [0.44 - 2.66]"], ["0.16", "0.19", "0.014", "0.11", "0.90", "0.87"], ["Second breast cancer", "1.33 [0.64 - 2.75]", "0.58 [0.37 - 0.92]", "4.09 [2.31 - 7.26]", "1.81 [0.82 - 3.96]", "0.61 [0.36 - 1.04]", "4.39 [2.17 - 8.87]"], ["0.44", "0.019", "1.4E-06", "0.14", "0.067", "3.8E-05"], ["(c) Patients with lobular breast cancer", "Univariate analysis", ""], ["I157T/nc"], ["Early death", "0.67 [0.39 - 1.15]"], ["0.14"], ["Breast cancer-specific death", "0.91 [0.46 - 1.80]"], ["0.79"], ["Distant metastasis relapse", "0.87 [0.48 - 1.57]"], ["0.64"], ["Locoregional relapse", "2.45 [0.95 - 6.34]"], ["0.065"], ["Second breast cancer", "1.92 [0.57 - 6.49]"], ["0.29"]], "row_count": 36, "column_count": 7, "numeric_cells": 143, "header_rows": 0, "locator": "section[12]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:27716369:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2e8816a6a370b241fe0d9c52cd5c54c0d73f2bf3654adb5a7bd073c4da8663f4", "bytes": 1762, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#Tab4", "version": null, "note": "Differentially expressed genes in breast tumors of p.I157T carriers when compared to non-carrier tumors", "structure": {"pmcid": "PMC5048645", "section_index": 13, "section_title": "P.I157T associated differentially expressed genes", "row_count": 22, "column_count": 5}, "table": {"label": "Table 4", "caption": "Differentially expressed genes in breast tumors of p.I157T carriers when compared to non-carrier tumors", "rows": [["Gene ID", "Symbol", "Description", "logFC", "p value"], ["11283", "CYP4F8", "Cytochrome P450, family 4, subfamily F, polypeptide 8", "1.10", "0.00026"], ["1289", "COL5A1", "Collagen, type V, alpha 1", "1.24", "0.00049"], ["1292", "COL6A2", "Collagen, type VI, alpha 2", "0.90", "0.00056"], ["56265", "CPXM1", "Carboxypeptidase X (M14 family), member 1", "1.04", "0.00063"], ["1277", "COL1A1", "Collagen, type I, alpha 1", "1.25", "0.0011"], ["23452", "ANGPTL2", "Angiopoietin-like 2", "0.85", "0.0020"], ["5118", "PCOLCE", "Procollagen C-endopeptidase enhancer", "0.90", "0.0021"], ["284297", "SSC5D", "Scavenger receptor cysteine rich family, 5 domains", "0.84", "0.0025"], ["25903", "OLFML2B", "Olfactomedin-like 2B", "0.88", "0.0026"], ["27239", "GPR162", "G protein-coupled receptor 162", "0.73", "0.0026"], ["5654", "HTRA1", "HtrA serine peptidase 1", "0.96", "0.0027"], ["9315", "NREP", "Neuronal regeneration-related protein", "0.78", "0.0028"], ["1278", "COL1A2", "Collagen, type I, alpha 2", "1.02", "0.0046"], ["8510", "MMP23B", "Matrix metallopeptidase 23B", "0.73", "0.0055"], ["114902", "C1QTNF5", "C1q and tumor necrosis factor-related protein 5", "0.77", "0.0057"], ["6678", "SPARC", "Secreted protein, acidic, cysteine-rich (osteonectin)", "0.88", "0.0073"], ["9622", "KLK4", "Kallikrein-related peptidase 4", "1.03", "0.0082"], ["1291", "COL6A1", "Collagen, type VI, alpha 1", "0.92", "0.0084"], ["1307", "COL16A1", "Collagen, type XVI, alpha 1", "0.73", "0.0090"], ["1290", "COL5A2", "Collagen, type V, alpha 2", "0.93", "0.0095"], ["7070", "THY1", "Thy-1 cell surface antigen", "0.88", "0.0098"]], "row_count": 22, "column_count": 5, "numeric_cells": 84, "header_rows": 1, "locator": "section[13]/table-wrap[1]#Tab4"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models."}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GEO: GSE24450"], "resolved_accessions": [], "statements": ["The dataset supporting the conclusions of this article is available in the Gene Expression Omnibus (GEO) repository, GEO: GSE24450, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24450."], "basis": "The paper names GEO: GSE24450, but the accession does not resolve in the repository (no reason recorded), so the data cannot be reached from here. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:27716369", "asset:table:pmid:27716369:1", "asset:table:pmid:27716369:2", "asset:table:pmid:27716369:3", "asset:table:pmid:27716369:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "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": "2026-10-31T18:29:32Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 8, "usage": {"prompt_tokens": 105763, "completion_tokens": 4347, "cached_tokens": 1560}}, "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:27716369", "type": "paper", "label": "pmid:27716369"}, {"id": "source:pmid:27716369", "type": "manuscript", "label": "PMID 27716369 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:27716369", "type": "paper", "label": "pmid:27716369"}, {"id": "source:pmid:27716369", "type": "manuscript", "label": "PMID 27716369 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-27716369", "type": "extraction", "used": ["source:pmid:27716369"], "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:27716369", "parent_hash": "sha256:5bb2304edac4fe5def58fd66c0c5b5ac30a720ff2db7610deb0ef20f4cde105f", "fork_of": null, "generation": 5}, "gaps": ["execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models."], "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":"2026-11-04T03:37:04+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}}}