{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33568149", "kind": "science-record", "revision": 7, "content_hash": "sha256:26a89902300d93a17f1e2b95c64a758884753aa9981fe51f7072c90831e8528f", "created_at": "2026-11-01T15:41:24Z", "updated_at": "2026-11-01T22:03:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Isotypes of autoantibodies against novel differential 4-hydroxy-2-nonenal-modified peptide adducts in serum is associated with rheumatoid arthritis in Taiwanese women.", "doi": "10.1186/s12911-020-01380-y", "pmid": "33568149", "authors": ["Kai-Leun Tsai", "Che-Chang Chang", "Yu-Sheng Chang", "Yi-Ying Lu", "I-Jung Tsai", "Jin-Hua Chen", "Sheng-Hong Lin", "Chih-Chun Tai", "Yi-Fang Lin", "Hui-Wen Chang", "Ching-Yu Lin", "Emily Chia-Yu Su"], "journal": "BMC medical informatics and decision making", "year": 2021, "abstract": "BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder with systemic inflammation and may be induced by oxidative stress that affects an inflamed joint. Our objectives were to examine isotypes of autoantibodies against 4-hydroxy-2-nonenal (HNE) modifications in RA and associate them with increased levels of autoantibodies in RA patients.\nMETHODS: Serum samples from 155 female patients [60 with RA, 35 with osteoarthritis (OA), and 60 healthy controls (HCs)] were obtained. Four novel differential HNE-modified peptide adducts, complement factor H (CFAH)1211-1230, haptoglobin (HPT)78-108, immunoglobulin (Ig) kappa chain C region (IGKC)2-19, and prothrombin (THRB)328-345, were re-analyzed using tandem mass spectrometric (MS/MS) spectra (ProteomeXchange: PXD004546) from RA patients vs. HCs. Further, we determined serum protein levels of CFAH, HPT, IGKC and THRB, HNE-protein adducts, and autoantibodies against unmodified and HNE-modified peptides. Significant correlations and odds ratios (ORs) were calculated.\nRESULTS: Levels of HPT in RA patients were greatly higher than the levels in HCs. Levels of HNE-protein adducts and autoantibodies in RA patients were significantly greater than those of HCs. IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgM anti-IGKC2-19 HNE may be considered as diagnostic biomarkers for RA. Importantly, elevated levels of IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 were positively correlated with the disease activity score in 28 joints for C-reactive protein (DAS28-CRP). Further, the ORs of RA development through IgM anti-HPT78-108 HNE (OR 5.235, p < 0.001), IgM anti-IGKC2-19 (OR 12.655, p < 0.001), and IgG anti-THRB328-345 (OR 5.761, p < 0.001) showed an increased risk. Lastly, we incorporated three machine learning models to differentiate RA from HC and OA, and performed feature selection to determine discriminative features. Experimental results showed that our proposed method achieved an area under the receiver operating characteristic curve of 0.92, which demonstrated that our selected autoantibodies combined with machine learning can efficiently detect RA.\nCONCLUSIONS: This study discovered that some IgG- and IgM-NAAs and anti-HNE M-NAAs may be correlated with inflammation and disease activity in RA. Moreover, our findings suggested that IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 may play heavy roles in RA development.", "claims": [{"id": "claim-method", "statement": "As shown in Table 4, an age adjusted logistic regression analysis demonstrated that ORs of RA development were significantly associated with levels of autoantibodies against unmodified and HNE-modified peptides in patients with RA compared to HCs", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33568149", "locator": "sections[15] \"Associations of serum anti-unmodified and anti-HNE-modified peptide autoantibodies with RA patients compared to HCs\" paragraph 2", "quote": "As shown in Table 4, an age adjusted logistic regression analysis demonstrated that ORs of RA development were significantly associated with levels of autoantibodies against unmodified and HNE-modified peptides in patients with RA compared to HCs"}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33568149", "locator": "sections[25] \"Availability of data and materials\" paragraph 2", "quote": "The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33568149"], "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:PXD004546"], "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:PXD004546"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33568149", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12911-020-01380-y", "sha256": "sha256:aa53decd4648b9e66cc0e00ba7044efaea6b2c6aa42557f5746c25a972bf6271", "bytes": 72417, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12911-020-01380-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7874460", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD004546", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD004546", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD004546", "version": null, "note": "The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Human Rheumatoid Arthritis LC-MSMS", "resolution_checked_at": "2026-10-31T18:35:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33568149:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9d4059dc3aa6f09919239c13474bec468b3d0fbabd72fe9b3543781606598c74", "bytes": 1271, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#Tab1", "version": null, "note": "Differential 4-hydroxy-2-nonenal (HNE)-modified peptide adducts in rheumatoid arthritis (RA) patients compared to healthy controls (HCs)", "structure": {"pmcid": "PMC7874460", "section_index": 13, "section_title": "Measuring autoantibodies against unmodified and HNE-modified peptides", "row_count": 11, "column_count": 9}, "table": {"label": "Table 1", "caption": "Differential 4-hydroxy-2-nonenal (HNE)-modified peptide adducts in rheumatoid arthritis (RA) patients compared to healthy controls (HCs)", "rows": [["Proteina", "Modified peptideb", "Positionc", "Obs.d", "Calc.e", "dMf", "dMg", "Sequence foundwith modifications"], ["HC", "RA"], ["CFAH", "SHTLRTTCWDGKLEYPTCAK(+ 158)", "1211–1230", "858.439", "858.435", "0.0041", "5.4", "−", "+"], ["HRTGDEITYQCRNGFYPATRGNTAK(+ 138)", "284–308", "749.370", "749.372", "− 0.0018", "−1.8", "+", "−"], ["HPT", "AVGDKLPECEADDGC(+ 158)PKPPEIAHGYVEHSVR", "78–108", "869.925", "869.927", "− 0.0017", "−1.3", "−", "+"], ["ILGGHLDA(+ 156)K", "162–170", "540.329", "540.327", "0.0028", "6.1", "+", "−"], ["IGKC", "TVAA(+ 156)PSVFIFPPSDEQLK", "2–19", "701.384", "701.386", "− 0.0018", "−1.7", "−", "+"], ["TVA(+ 156)APSVFIFPPSDEQLK", "2–19", "1051.582", "1051.575", "0.0070", "7.1", "+", "+"], ["VYACEVTHQ(+ 158)GLSSPVTKSFNR", "83–103", "862.780", "862.785", "− 0.0044", "−4.5", "+", "−"], ["THRB", "TFGSGEADCGLRPLFEK(+ 156)K", "328–345", "1056.036", "1056.046", "− 0.0107", "−9.6", "−", "+"], ["TFGSGEADC(+ 140)GLRPL(+ 156)FEK", "328–344", "708.376", "708.375", "0.0009", "2.1", "+", "−"]], "row_count": 11, "column_count": 9, "numeric_cells": 54, "header_rows": 2, "locator": "section[13]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:33568149:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f49ea03d5d8f9e0e1ad1b5040350090796c410eff7eadeed5b22abf8c80b9fdc", "bytes": 4141, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#Tab2", "version": null, "note": "Comparisons of the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides in rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients compared to healthy controls (HCs)", "structure": {"pmcid": "PMC7874460", "section_index": 13, "section_title": "Measuring autoantibodies against unmodified and HNE-modified peptides", "row_count": 34, "column_count": 8}, "table": {"label": "Table 2", "caption": "Comparisons of the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides in rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients compared to healthy controls (HCs)", "rows": [["Peptides", "RA vs. HC", "OA versus HC", "p value a"], ["AUC (95%CI)", "Sensitivity (95%CI)", "Specificity (95%CI)", "AUC (95%CI)", "Sensitivity (95%CI)", "Specificity (95%CI)"], ["IgG anti-CFAH1121−1230", "0.66 (0.57–0.76)", "63.3% (49.9–75.4)", "51.7% (38.4–64.8)", "0.58 (0.46–0.70)", "60.0% (42.1–76.1)", "60.0% (46.5–72.4)", "0.6844"], ["Cutoff (OD450)", "", "> 0.24", "", "", "< 0.21", "", ""], ["IgG anti-CFAH1121−1230 HNE", "0.71 (0.62–0.80)", "76.7% (64.0–86.6)", "55.0% (41.6–67.9)", "0.52 (0.40–0.64)", "51.4% (34.0–68.6)", "50.0% (36.8–63.2)", "0.0135"], ["Cutoff (OD450)", "", "> 0.21", "", "", "< 0.20", "", ""], ["IgM anti-CFAH1121−1230", "0.68 (0.59–0.78)", "81.7% (69.6–90.5)", "53.3% (40.0–66.3)", "0.68 (0.58–0.79)", "77.1% (59.9–89.6)", "60.0% (46.5–72.4)", "0.4816"], ["Cutoff (OD450)", "", "> 0.58", "", "", "> 0.63", "", ""], ["IgM anti-CFAH1121−1230 HNE", "0.70 (0.61–0.79)", "85.0% (73.4–92.9)", "41.7% (29.1–55.1)", "0.59 (0.47–0.71)", "80.0% (63.1–91.6)", "36.7% (24.6–50.1)", "0.0421"], ["Cutoff (OD450)", "", "> 0.24", "", "", "> 0.23", "", ""], ["IgG anti-HPT78−108", "0.67 (0.58–0.77)", "71.7% (58.6–82.6)", "55.0% (41.6–67.9)", "0.53 (0.41–0.65)", "51.4% (34.0–68.6)", "46.7% (33.7–60.0)", "0.3711"], ["Cutoff (OD450)", "", "> 0.64", "", "", "< 0.64", "", ""], ["IgG anti-HPT78−108 HNE", "0.66 (0.57–0.76)", "71.7% (58.6–82.6)", "48.3% (35.2–61.6)", "0.58 (0.46–0.70)", "62.9% (44.9–78.5)", "55.0% (41.6–67.9)", "0.8974"], ["Cutoff (OD450)", "", "> 0.25", "", "", "< 0.25", "", ""], ["IgM anti-HPT78−108", "0.67 (0.57–0.77)", "71.7% (58.6–82.6)", "56.7% (43.2–69.4)", "0.53(0.40–0.66)", "51.4%(33.9–68.6)", "50.0%(36.8– 63.2)", "0.2823"], ["Cutoff (OD450)", "", "> 0.30", "", "", "< 0.29", "", ""], ["IgM anti-HPT78−108 HNE", "0.89 (0.80–0.93)", "86.7% (75.4–94.1)", "66.7% (53.3–78.3)", "0.58 (0.46–0.69)", "65.7% (47.8–80.9)", "55.0% (41.6–67.9)", "< 0.0001"], ["Cutoff (OD450)", "", "> 0.20", "", "", "> 0.16", "", ""], ["IgG anti-IGKC2−19", "0.72 (0.62–0.81)", "80.0% (67.7–89.2)", "60.0% (46.5–72.4)", "0.59 (0.47–0.70)", "65.7% (47.8–80.9)", "53.3% (40.0–66.3)", "0.1471"], ["Cutoff (OD450)", "", "> 0.41", "", "", "> 0.37", "", ""], ["IgG anti-IGKC2−19 HNE", "0.70 (0.61–0.79)", "78.3% (65.8–87.9)", "56.7% (43.2–69.4)", "0.55 (0.43–0.67)", "65.7% (47.9–80.9)", "50.0% (36.8–63.2)", "0.0917"], ["Cutoff (OD450)", "", "> 0.45", "", "", "> 0.39", "", ""], ["IgM anti-IGKC2−19", "0.83 (0.75–0.90)", "81.7% (69.6–90.5)", "60.0% (46.5–72.4)", "0.56 (0.44–0.68)", "57.1% (39.4–73.7)", "50.0% (36.8–63.2)", "< 0.0001"], ["Cutoff (OD450)", "", "> 0.61", "", "", "> 0.53", "", ""], ["IgM anti-IGKC2−19 HNE", "0.86 (0.79–0.93)", "83.3% (71.5–91.7)", "66.7% (53.3–78.3)", "0.58 (0.46–0.70)", "68.6% (50.7–83.2)", "51.7% (38.4–64.8)", "< 0.0001"], ["Cutoff (OD450)", "", "> 0.37", "", "", "> 0.32", "", ""], ["IgG anti-THRB328−345", "0.70 (0.61–0.79)", "66.7% (53.3–78.3)", "53.3% (40.0–66.3)", "0.53 (0.42–0.65)", "62.9% (44.9–78.5)", "48.3% (35.2–61.6)", "0.0086"], ["Cutoff (OD450)", "", "> 0.20", "", "", "> 0.19", "", ""], ["IgG anti-THRB328−345 HNE", "0.75 (0.67–0.84)", "80.0% (67.7–89.2)", "53.3% (40.0–66.3)", "0.60 (0.48–0.71)", "68.6% (50.7–83.2)", "50.0% (36.8–63.2)", "0.0087"], ["Cutoff (OD450)", "", "> 0.32", "", "", "> 0.31", "", ""], ["IgM anti-THRB328−345", "0.63 (0.53–0.73)", "63.3% (50.0–75.4)", "53.3% (40.0–66.3)", "0.56 (0.44–0.68)", "60.0% (42.1–76.1)", "53.3% (40.0–66.3)", "0.5845"], ["Cutoff (OD450)", "", "> 0.61", "", "", "> 0.60", "", ""], ["IgM anti-THRB328−345 HNE", "0.78 (0.69–0.86)", "76.7% (64.0–86.6)", "71.7% (58.6–82.6)", "0.56 (0.44–0.68)", "65.7% (47.8–80.9)", "46.7% (33.7–60.0)", "0.0001"], ["Cutoff (OD450)", "", "> 0.64", "", "", "> 0.52", "", ""]], "row_count": 34, "column_count": 8, "numeric_cells": 182, "header_rows": 2, "locator": "section[13]/table-wrap[2]#Tab2"}}, {"id": "asset:table:pmid:33568149:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:fc8ce78dc9008b66d2779170f9ee12b3a82131de07dfc5cf2ebe99ea2c736523", "bytes": 2775, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#Tab3", "version": null, "note": "Correlations between autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides and clinical variables in rheumatoid arthritis (RA) patients (n = 60)", "structure": {"pmcid": "PMC7874460", "section_index": 14, "section_title": "Correlations of serum anti-unmodified and anti-HNE-modified peptide autoantibodies with clinical variables in RA patients", "row_count": 18, "column_count": 13}, "table": {"label": "Table 3", "caption": "Correlations between autoantibody isotypes against unmodified and 4-hydroxy-2-nonenal (HNE)-modified peptides and clinical variables in rheumatoid arthritis (RA) patients (n = 60)", "rows": [["", "DAS28", "RF", "Anti-CCP", "CRP", "ESR", "HNE adduct"], ["r", "p value", "r", "p value", "r", "p value", "r", "p value", "r", "p value", "r", "p value"], ["IgG anti-CFAH1121−1230", "0.1580", "0.2279", "0.0968", "0.4696", "0.0108", "0.9347", "0.0229", "0.8659", "0.2076", "0.1115", "− 0.009", "0.9458"], ["IgG anti-CFAH1121−1230 HNE", "− 0.0441", "0.7379", "− 0.0035", "0.9794", "− 0.0359", "0.7852", "− 0.1446", "0.2831", "0.1359", "0.3006", "− 0.0082", "0.9501"], ["IgM anti-CFAH1121−1230", "0.0424", "0.7477", "0.0626", "0.6406", "0.2100", "0.1073", "− 0.0164", "0.9036", "0.0756", "0.5658", "− 0.0503", "0.7026"], ["IgM anti-CFAH1121−1230HNE", "0.0377", "0.7748", "0.0435", "0.746", "0.2192", "0.0924", "− 0.0821", "0.5435", "0.1343", "0.3063", "0.0302", "0.8186"], ["IgG anti-HPT78−108", "0.0929", "0.4804", "0.1386", "0.2996", "0.0659", "0.6169", "0.1138", "0.3994", "0.1695", "0.1954", "0.0754", "0.5670"], ["IgG anti-HPT78−108 HNE", "− 0.0266", "0.8400", "0.0195", "0.8848", "0.2782", "0.0314", "0.1081", "0.4236", "0.1346", "0.3052", "− 0.0593", "0.6529"], ["IgM anti-HPT78−108", "− 0.0171", "0.8969", "0.1711", "0.1992", "0.0877", "0.5051", "− 0.0591", "0.6623", "0.0074", "0.9555", 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all 16 features in decision trees, random forests, and support vector machines for healthy controls (HCs) versus rheumatoid arthritis (RA) patients and osteoarthritis (OA) versus RA patients", "structure": {"pmcid": "PMC7874460", "section_index": 16, "section_title": "Using serum anti-unmodified and anti-HNE-modified peptide autoantibodies to identify RA patients from HCs and OA patients", "row_count": 9, "column_count": 7}, "table": {"label": "Table 6", "caption": "Predictive performance using all 16 features in decision trees, random forests, and support vector machines for healthy controls (HCs) versus rheumatoid arthritis (RA) patients and osteoarthritis (OA) versus RA patients", "rows": [["Algorithms*", "Accuracy", "Precision", "F1 score", "Sensitivity", "Specificity", "AUC"], ["HC v.s. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["PXD004546"], "resolved_accessions": ["PXD004546"], "statements": ["The data that support the findings of this study are available from Shuang-Ho Hospital (New Taipei City, Taiwan) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the hospital."], "basis": "The paper names PXD004546 in ProteomeXchange and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["glm_logit_fit"], "assets": ["source:pmid:33568149", "data:geo:PXD004546", "asset:table:pmid:33568149:1", "asset:table:pmid:33568149:2", "asset:table:pmid:33568149:3", "asset:table:pmid:33568149:4", "asset:table:pmid:33568149:5", "asset:table:pmid:33568149:6", "asset:table:pmid:33568149:7"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD004546"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:26:55Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 63427, "completion_tokens": 1702, "cached_tokens": 784}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:33568149", "type": "paper", "label": "pmid:33568149"}, {"id": "source:pmid:33568149", "type": "manuscript", "label": "PMID 33568149 full text"}, {"id": "data:geo:PXD004546", "type": "dataset", "label": "GEO PXD004546"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33568149", "type": "paper", "label": "pmid:33568149"}, {"id": "source:pmid:33568149", "type": "manuscript", "label": "PMID 33568149 full text"}, {"id": "data:geo:PXD004546", "type": "dataset", "label": "GEO PXD004546"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33568149", "type": "extraction", "used": ["source:pmid:33568149"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD004546", "type": "accession_resolution", "used": ["data:geo:PXD004546"], "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:33568149", "parent_hash": "sha256:f4cc68beafdba99605c355bc4123fa7cd70ed0b4f83677bf812be604e95ee134", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:PXD004546 licence not read", "asset:data:geo:PXD004546 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["(THRB)328-345, were re-analyzed using tandem mass spectrometric (MS/MS) spectra (ProteomeXchange: PXD004546)", "s), 1-D SDS-PAGE, in-gel digestion, and nano-LC-MS/MS (A). HNE reacts with amino acid residues of"], "order_basis": "paper_text_order:838", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": [") [6]. Their protein levels were examined by Western blotting with individual randomly age paired serum fr", "ssessed through immunoprecipitation (IP) and Western blotting using the pooled Con A-captured serum sample"], "order_basis": "paper_text_order:4227", "id": "assay:2"}, {"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["glm_logit_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["As shown in Table 4, an age adjusted logistic regression analysis demonstrated that ORs of RA development were significantly associated with levels of autoantibodies against unmodified and HNE-modified peptides in patients with RA compared to HCs"], "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":"2026-11-04T03:14:20+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}}}