{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34424905", "kind": "science-record", "revision": 7, "content_hash": "sha256:5acc1cbcd259105efa3daa31e964f5c7557c51b2e12570dfdc5155b3acc4f6ca", "created_at": "2026-11-01T15:41:49Z", "updated_at": "2026-11-01T22:04:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.", "doi": "10.1371/journal.pntd.0009714", "pmid": "34424905", "authors": ["Amanda Ribeiro Dos Santos", "Aline Dionizio", "Mileni da Silva Fernandes", "Marília Afonso Rabelo Buzalaf", "Beatriz Pereira", "Débora de Fátima Almeida Donanzam", "Sergio Marrone Ribeiro", "Anamaria Mello Miranda Paniago", "Ricardo de Souza Cavalcante", "Rinaldo Poncio Mendes", "James Venturini"], "journal": "PLoS neglected tropical diseases", "year": 2021, "abstract": "BACKGROUND: Pulmonary sequelae (PS) in patients with chronic paracoccidioidomycosis (PCM) typically include pulmonary fibrosis and emphysema. Knowledge of the molecular pathways involved in PS of PCM is required for treatment and biomarker identification.\nMETHODOLOGY/PRINCIPAL FINDINGS: This non-concurrent cohort study included 29 patients with pulmonary PCM that were followed before and after treatment. From this group, 17 patients evolved to mild/ moderate PS and 12 evolved severe PS. Sera from patients were evaluated before treatment and at clinical cure, serological cure, and apparent cure. A nanoACQUITY UPLC-Xevo QT MS system and PLGS software were used to identify serum differentially expressed proteins, data are available via ProteomeXchange with identifier PXD026906. Serum differentially expressed proteins were then categorized using Cytoscape software and the Reactome pathway database. Seventy-two differentially expressed serum proteins were identified in patients with severe PS compared with patients with mild/moderate PS. Most proteins altered in severe PS were involved in wound healing, inflammatory response, and oxygen transport pathways. Before treatment and at clinical cure, signaling proteins participating in wound healing, complement cascade, cholesterol transport and retinoid metabolism pathways were downregulated in patients with severe PS, whereas signaling proteins in gluconeogenesis and gas exchange pathways were upregulated. At serological cure, the pattern of protein expression reversed. At apparent cure pathways related with tissue repair (fibrosis) became downregulated, and pathway related oxygen transport became upregulated. Additionally, we identified 15 proteins as candidate biomarkers for severe PS.\nCONCLUSIONS/SIGNIFICANCE: Development of severe PS is related to increased expression of proteins involved in glycolytic pathway and oxygen exchange), indicative of the greater cellular activity and replication associated with early dysregulation of wound healing and aberrant tissue repair. Our findings provide new targets to study mechanisms of PS in PCM, as well as potential biomarkers.", "claims": [{"id": "claim-method", "statement": "To determine differences serum proteins expression between PCM patients with severe and mild/moderate PS in each stage of clinical follow-up, ProteinLynx Global Server (PLGS) Expression E software was used, with p < 0.05 and p > 0.95 used to identify downregulation and upregulation of proteins, respectively, as reported earlier [40].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34424905", "locator": "sections[7] \"LC-MS/MS and bioinformatics analyses\" paragraph 2", "quote": "To determine differences serum proteins expression between PCM patients with severe and mild/moderate PS in each stage of clinical follow-up, ProteinLynx Global Server (PLGS) Expression E software was used, with p < 0.05 and p > 0.95 used to identify downregulation and upregulation of proteins, respectively, as reported earlier [40]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the manuscript and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34424905", "locator": "sections[20] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the manuscript and its Supporting Information files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:34424905"], "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:PXD026906"], "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": ["data:geo:PXD026906"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34424905", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pntd.0009714", "sha256": "sha256:9bda7eec581d6293cbbe590e834a041120ce686b16e1b24fecfd5b01c7f9d36b", "bytes": 65309, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pntd.0009714", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8425554", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD026906", "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=PXD026906", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD026906", "version": null, "note": "All relevant data are within the manuscript and its Supporting Information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All relevant data are within the manuscript and its Supporting Information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel", "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:34424905:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b485a280c508376f11b8a24a312da897bf8df166dc83418f43e1257fea3498b7", "bytes": 1466, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#pntd.0009714.t001", "version": null, "note": "Clinical aspects of paracoccidioidomycosis patients distributed according of pulmonar sequel (PS) intensity. N (%).", "structure": {"pmcid": "PMC8425554", "section_index": 5, "section_title": "Procedures", "row_count": 22, "column_count": 6}, "table": {"label": "Table 1", "caption": "Clinical aspects of paracoccidioidomycosis patients distributed according of pulmonar sequel (PS) intensity. N (%).", "rows": [["Clinical Aspects", "Patients (n = 29)", "Mild/moderate PS (n = 17)", "Severe PS (n = 12)", "p value"], ["Age (years) 1", "50", "56", "57", "0.8003"], ["Levels of severity 2", "Mild", "2 (6.9)", "2 (11.7)", "0 (0)", "1.000"], ["Moderate", "23 (79.3)", "13 (76.4)", "10 (83.3)"], ["Severe", "4 (13.8)", "2 (11.7)", "2 (16.6)"], ["Affected organs 2", "Adrenal", "3 (10.3)", "1 (5.88)", "2 (16.6)", "0.367"], ["CNS", "3 (10.3)", "3 (17.6)", "0 (0)", "0.186"], ["Mucosa", "5 (51.7)", "9(52.9)", "6 (50)", "0.586"], ["Skin", "1 (3.4)", "1 (5.88)", "0 (0)", "0.586"], ["Lung", "29 (100)", "17 (100)", "12 (100)", "UR"], ["Larynx", "5 (17.2)", "2 (11.7)", "3(25)", "0.329"], ["Lymphnode", "4 (13.8)", "4 (23.5)", "0 (0)", "0.100"], ["Bone", "1 (3.4)", "0 (0)", "1 (8.33)", "0.413"], ["Antifungal treatment 2", "CMX", "17 (58.6)", "11 (64.7)", "6 (50)", "0.5368"], ["CMX–ITC", "4 (13.8)", "4 (23.5)", "0 (0)"], ["ITC", "3 (10.3)", "1 (5.88)", "2 (16.6)"], ["ITC- CMX", "2 (6.9)", "0 (0)", "2 (16.6)"], ["Others", "3 (10.3)", "2 (11.7)", "1 (8.3)"], ["Time of treatment (months) 1", "38", "28", "44", "0.2871"], ["Time for clinical cure (days) 1", "142", "149", "126", "0.2687"], ["Time for serological cure (days) 1 . 3", "530", "314.5", "825", "0.2679"], ["DID 1", "1:16", "1:16", "1:8", "0.9463"]], "row_count": 22, "column_count": 6, "numeric_cells": 88, "header_rows": 1, "locator": "section[5]/table-wrap[1]#pntd.0009714.t001"}}, {"id": "asset:table:pmid:34424905:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:228df5ee8f59bb078dc820fe3114c6bb14b423ac493f7aaf50953eb47b293935", "bytes": 3476, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[1]#pntd.0009714.t002", "version": null, "note": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in the moment of before treatment (S0).", "structure": {"pmcid": "PMC8425554", "section_index": 7, "section_title": "LC-MS/MS and bioinformatics analyses", "row_count": 58, "column_count": 4}, "table": {"label": "Table 2", "caption": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in the moment of before treatment (S0).", "rows": [["aAccess number", "Protein name", "PLGS Score", "bRatio (severe PS:mild/moderate PS)"], ["P68871", "Hemoglobin subunit beta", "5774", "2.34"], ["P69892", "Hemoglobin subunit gamma-2", "2216", "2.32"], ["P02042", "Hemoglobin subunit delta", "2216", "2.29"], ["P02100", "Hemoglobin subunit epsilon", "2216", "2.27"], ["P69891", "Hemoglobin subunit gamma-1", "2216", "2.25"], ["P69905", "Hemoglobin subunit alpha", "4673", "2.16"], ["P06733", "Alpha-enolase", "556", "1.30"], ["P09104", "Gamma-enolase", "556", "1.30"], ["P13929", "Beta-enolase", "556", "1.30"], ["P02766", "Transthyretin", "3869", "1.17"], ["P02750", "Alpha-2-HS-glycoprotein", "1470", "0.88"], ["P00739", "Apolipoprotein A-I", "5802", "0.87"], ["P00738", "Serotransferrin", "52105", "0.82"], ["P01023", "Kininogen-1", "436", "0.80"], ["P20742", "Prothrombin", "362", "0.80"], ["P01011", "Inter-alpha-trypsin inhibitor heavy chain H4", "94", "0.79"], ["P02749", "Inter-alpha-trypsin inhibitor heavy chain H2", "769", "0.76"], ["P01009", "Clusterin", "762", "0.72"], ["P0C0L4", "Inter-alpha-trypsin inhibitor heavy chain H1", "228", "0.72"], ["P0C0L5", "Heparin cofactor 2", "96", "0.68"], ["P02760", "Vitronectin", "455", "0.67"], ["P04217", "Complement factor H", "299", "0.66"], ["P01024", "Vitamin D-binding protein", "1196", "0.64"], ["P02790", "Putative hydroxypyruvate isomerase", "163", "0.63"], ["P00747", "Ceruloplasmin", "603", "0.61"], ["P00450", "Complement factor B", "1014", "0.61"], ["P00751", "Hemopexin", "3711", "0.60"], ["Q5T013", "Plasminogen", "238", "0.60"], ["P02774", "Complement C3", "9892", "0.59"], ["P08603", "Alpha-1B-glycoprotein", "995", "0.58"], ["P04004", "Protein AMBP", "607", "0.53"], ["P05546", "Complement C4-B", "316", "0.52"], ["P10909", "Alpha-1-antitrypsin", "3334", "0.51"], ["P19827", "Complement C4-A", "316", "0.51"], ["P19823", "Beta-2-glycoprotein 1", "847", "0.51"], ["Q14624", "Alpha-1-antichymotrypsin", "1432", "0.50"], ["P01042", "Pregnancy zone protein", "196", "0.47"], ["P00734", "Alpha-2-macroglobulin", "4747", "0.44"], ["P02787", "Haptoglobin", "19050", "0.43"], ["P02647", "Haptoglobin-related protein", "8443", "0.43"], ["P02765", "Leucine-rich alpha-2-glycoprotein", "124", "0.36"], ["*Q6DKI1", "60S ribosomal protein L7-like 1", "34", "Severe PS*"], ["P01019", "Angiotensinogen", "109", "Severe PS"], ["P01031", "Complement C5", "32", "Severe PS"], ["Q9H6N6", "Putative uncharacterized protein MYH16", "49", "Severe PS"], ["Q6ZNX1", "Shieldin complex subunit 3", "36", "Severe PS"], 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"asset:table:pmid:34424905:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ee8b3ffb62082110af27a198196533df49dd4ccac01be5dfb8852ae31dc71b47", "bytes": 2261, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[2]#pntd.0009714.t003", "version": null, "note": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in the moment of clinical cure (S1).", "structure": {"pmcid": "PMC8425554", "section_index": 7, "section_title": "LC-MS/MS and bioinformatics analyses", "row_count": 39, "column_count": 4}, "table": {"label": "Table 3", "caption": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in the moment of clinical cure (S1).", "rows": [["aAccess number", "Protein name", "PLGS Score", "bRatio (severe PS:mild/moderate PS)"], ["P69905", "Hemoglobin subunit alpha", "2896", "1.72"], ["P02787", "Serotransferrin", "44194", "1.30"], ["P00738", "Haptoglobin", "21516", "1.16"], ["P00739", "Haptoglobin-related protein", "10216", "1.14"], ["P68871", "Hemoglobin subunit beta", "4951", "1.11"], ["P04217", "Alpha-1B-glycoprotein", "948", "0.93"], ["P01011", "Alpha-1-antichymotrypsin", "2832", "0.90"], ["P08603", "Complement factor H", "284", "0.88"], ["P19827", "Inter-alpha-trypsin inhibitor heavy chain H1", "328", "0.87"], ["P02774", "Vitamin D-binding protein", "2264", "0.87"], ["P02751", "Fibronectin", "94", "0.86"], ["P00747", "Plasminogen", "308", "0.85"], ["P02749", "Beta-2-glycoprotein 1", "905", "0.84"], ["P0C0L4", "Complement C4-A", "470", "0.84"], ["P0C0L5", "Complement C4-B", "470", "0.84"], ["P05546", "Heparin cofactor 2", "94", "0.84"], ["P04004", "Vitronectin", "763", "0.82"], ["P01024", "Complement C3", "11714", "0.81"], ["P19823", "Inter-alpha-trypsin inhibitor heavy chain H2", "868", "0.79"], ["P01023", "Alpha-2-macroglobulin", "8579", "0.79"], ["P20742", "Pregnancy zone protein", "378", "0.79"], ["P00450", "Ceruloplasmin", "1877", "0.78"], ["P01042", "Kininogen-1", "320", "0.77"], ["P02760", "Protein AMBP", "590", "0.76"], ["P01008", "Antithrombin-III", "145", "0.75"], ["P02790", "Hemopexin", "4428", "0.72"], ["P01009", "Alpha-1-antitrypsin", "5216", "0.70"], ["P00734", "Prothrombin", "501", "0.70"], ["P10909", "Clusterin", "697", "0.69"], ["P06727", "Apolipoprotein A-IV", "131", "0.65"], ["P02766", "Transthyretin", "1202", "0.62"], ["P02647", "Apolipoprotein A-I", "4009", "0.58"], ["P02656", "Apolipoprotein C-III", "1698", "0.36"], ["P02763", "Alpha-1-acid glycoprotein 1", "157", "Severe PS*"], ["P01019", "Angiotensinogen", "272", "Mild/moderate PS"], ["P02649", "Apolipoprotein E", "130", "Mild/moderate PS"], ["P02753", "Retinol-binding protein 4", "437", "Mild/moderate PS"], ["P27169", "Serum paraoxonase/arylesterase 1", "1266", "Mild/moderate PS"]], "row_count": 39, "column_count": 4, "numeric_cells": 117, "header_rows": 1, "locator": "section[7]/table-wrap[2]#pntd.0009714.t003"}}, {"id": "asset:table:pmid:34424905:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b3ace37943dc64273c84f974146d63d5147eb7b7e0158d5983dd5dbf76b9d936", "bytes": 2705, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[3]#pntd.0009714.t004", "version": null, "note": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in moment of serological cure (S2).", "structure": {"pmcid": "PMC8425554", "section_index": 7, "section_title": "LC-MS/MS and bioinformatics analyses", "row_count": 47, "column_count": 4}, "table": {"label": "Table 4", "caption": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in moment of serological cure (S2).", "rows": [["aAccess number", "Protein name", "PLGS Score", "bRatio (severe PS:mild/moderate PS)"], ["P02751", "Fibronectin", "799", "2.32"], ["P05155", "Plasma protease C1 inhibitor", "561", "1.82"], ["P00739", "Haptoglobin-related protein", "7979", "1.39"], ["P00738", "Haptoglobin", "20464", "1.35"], ["Q14624", "Inter-alpha-trypsin inhibitor heavy chain H4", "56", "1.34"], ["Q5T013", "Putative hydroxypyruvate isomerase", "140", "1.32"], ["P02787", "Serotransferrin", "58693", "1.25"], ["P02765", "Alpha-2-HS-glycoprotein", "1410", "1.22"], ["P02750", "Leucine-rich alpha-2-glycoprotein", "280", "1.21"], ["P13929", "Beta-enolase", "1050", "1.19"], ["P09104", "Gamma-enolase", "1050", "1.19"], ["P01024", "Complement C3", "21361", "1.16"], ["P00751", "Complement factor B", "1405", "1.15"], ["P02790", "Hemopexin", "5861", "1.15"], ["P04004", "Vitronectin", "693", "1.15"], ["P04196", "Histidine-rich glycoprotein", "110", "1.15"], ["P05546", "Heparin cofactor 2", "158", "1.12"], ["P00747", "Plasminogen", "465", "1.09"], ["P01011", "Alpha-1-antichymotrypsin", "2056", "1.08"], ["P02647", "Apolipoprotein A-I", "8940", "1.07"], ["P10909", "Clusterin", "1717", "1.07"], ["P20742", "Pregnancy zone protein", "301", "1.06"], ["P02774", "Vitamin D-binding protein", "2536", "1.05"], ["P00450", "Ceruloplasmin", "1149", "1.04"], ["P01023", "Alpha-2-macroglobulin", "9840", "1.03"], ["P06727", "Apolipoprotein A-IV", "126", "0.91"], ["P0C0L4", "Complement C4-A", "470", "0.91"], ["P0C0L5", "Complement C4-B", "460", "0.90"], ["P02760", "Protein AMBP", "336", "0.89"], ["P01009", "Alpha-1-antitrypsin", "6126", "0.84"], ["P02749", "Beta-2-glycoprotein 1", "1341", "0.78"], ["P02763", "Alpha-1-acid glycoprotein 1", "225", "0.61"], ["P27169", "Serum paraoxonase/arylesterase 1", "726", "0.57"], ["P69905", "Hemoglobin subunit alpha", "386", "0.52"], ["P19652", "Alpha-1-acid glycoprotein 2", "123", "0.51"], ["P68871", "Hemoglobin subunit beta", "2416", "0.50"], ["P02042", "Hemoglobin subunit delta", "1332", "0.47"], ["P02100", "Hemoglobin subunit epsilon", "1332", "0.46"], ["P69891", "Hemoglobin subunit gamma-1", "1332", "0.46"], ["P69892", "Hemoglobin subunit gamma-2", "1332", "0.45"], ["P08697", "Alpha-2-antiplasmin", "689", "Severe PS*"], ["P02652", "Apolipoprotein A-II", "436", "Severe PS"], ["P02649", "Apolipoprotein E", "158", "Severe PS"], ["P0DJI8", "Serum amyloid A-1 protein", "3449", "Severe PS"], ["P0DJI9", "Serum amyloid A-2 protein", "544", "Severe PS"], ["Q15166", "Serum paraoxonase/lactonase 3", "4", "mild/moderate PS"]], "row_count": 47, "column_count": 4, "numeric_cells": 144, "header_rows": 1, "locator": "section[7]/table-wrap[3]#pntd.0009714.t004"}}, {"id": "asset:table:pmid:34424905:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4c6a6f0d41671704f6aacc1ca263ef956686ab628d62d108fc84498a24250811", "bytes": 2630, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#pntd.0009714.t005", "version": null, "note": "Proteins with expression significantly altered in the serum of Paracoccidioidomycosis patients with Severe and Mild/moderate pulmonary sequel (PS) as outcome in the moment of apparent cure.", "structure": {"pmcid": "PMC8425554", "section_index": 15, "section_title": "Reactome pathways analysis of serum proteins in severe PS patients, at apparent cure (S3)", "row_count": 45, "column_count": 4}, "table": {"label": "Table 5", "caption": "Proteins with expression significantly altered in the serum of Paracoccidioidomycosis patients with Severe and Mild/moderate pulmonary sequel (PS) as outcome in the moment of apparent cure.", "rows": [["aAccess number", "Protein name", "PLGS Score", "bRatio (Severe PS:mild/moderate PS)"], ["P69905", "Hemoglobin subunit alpha", "1823", "1.30"], ["P02790", "Hemopexin", "6961", "1.06"], ["P08603", "Complement factor H", "486", "0.88"], ["P00738", "Haptoglobin", "22790", "0.87"], ["P01023", "Alpha-2-macroglobulin", "6037", "0.85"], ["P00739", "Haptoglobin-related protein", "9541", "0.84"], ["P20742", "Pregnancy zone protein", "432", "0.84"], ["P00751", "Complement factor B", "1196", "0.83"], ["P02749", "Beta-2-glycoprotein 1", "1413", "0.78"], ["P02774", "Vitamin D-binding protein", "1889", "0.77"], ["P00747", "Plasminogen", "337", "0.76"], ["P04004", "Vitronectin", "705", "0.76"], ["Q96PD5", "N-acetylmuramoyl-L-alanine amidase", "144", "0.74"], ["P01042", "Kininogen-1", "732", "0.74"], ["P0C0L4", "Complement C4-A", "489", "0.73"], ["P0C0L5", "Complement C4-B", "488", "0.73"], ["P00734", "Prothrombin", "541", "0.73"], ["P05546", "Heparin cofactor 2", "93", "0.72"], ["P02766", "Transthyretin", "2160", "0.72"], ["P01011", "Alpha-1-antichymotrypsin", "1925", "0.71"], ["P04217", "Alpha-1B-glycoprotein", "999", "0.68"], ["P00450", "Ceruloplasmin", "2315", "0.66"], ["P01024", "Complement C3", "13144", "0.66"], ["P19827", "Inter-alpha-trypsin inhibitor heavy chain H1", "1036", "0.66"], ["P01019", "Angiotensinogen", "117", "0.65"], ["P02760", "Protein AMBP", "495", "0.65"], ["P02787", "Serotransferrin", "45136", "0.65"], ["Q14624", "Inter-alpha-trypsin inhibitor heavy chain H4", "147", "0.64"], ["P19823", "Inter-alpha-trypsin inhibitor heavy chain H2", "1325", "0.63"], ["Q5T013", "Putative hydroxypyruvate isomerase", "72", "0.60"], ["P02656", "Apolipoprotein C-III", "4030", "0.59"], ["P02765", "Alpha-2-HS-glycoprotein", "2620", "0.58"], ["P10909", "Clusterin", "823", "0.58"], ["P06727", "Apolipoprotein A-IV", "155", "0.56"], ["P01009", "Alpha-1-antitrypsin", "4246", "0.55"], ["P02647", "Apolipoprotein A-I", "8083", "0.52"], ["P01008", "Antithrombin-III", "156", "Severe PS*"], ["P43652", "Afamin", "120", "mild/moderate PS"], ["P02763", "Alpha-1-acid glycoprotein 1", "279", "mild/moderate PS"], ["P02652", "Apolipoprotein A-II", "547", "mild/moderate PS"], ["P02649", "Apolipoprotein E", "486", "mild/moderate PS"], ["P09871", "Complement C1s subcomponent", "65", "mild/moderate PS"], ["P05155", "Plasma protease C1 inhibitor", "90", "mild/moderate PS"], ["P27169", "Serum paraoxonase/arylesterase 1", "857", "mild/moderate PS"]], "row_count": 45, "column_count": 4, "numeric_cells": 132, "header_rows": 1, "locator": "section[15]/table-wrap[1]#pntd.0009714.t005"}}], "gaps": ["asset:data:geo:PXD026906 not downloaded", "asset:data:geo:PXD026906 licence not read"]}, "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": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "pathway enrichment"}}, {"id": "method-3", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "Chi-square"}}, {"id": "method-4", "family": null, "specific": null, "label": "ProteinLynx Global Server (PLGS) Expression E algorithm", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To determine differences serum proteins expression between PCM patients with severe and mild/moderate PS in each stage of clinical follow-up, ProteinLynx Global Server (PLGS) Expression E software was used, with p < 0.05 and p > 0.95 used to identify downregulation and upregulation of proteins, respectively, as reported earlier [40]."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "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": "R1", "reachable": true, "accessions": ["PXD026906"], "resolved_accessions": ["PXD026906"], "statements": ["All relevant data are within the manuscript and its Supporting Information files."], "basis": "The paper names PXD026906 in ProteomeXchange Consortium via the PRIDE partner repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:34424905", "data:geo:PXD026906", "asset:table:pmid:34424905:1", "asset:table:pmid:34424905:2", "asset:table:pmid:34424905:3", "asset:table:pmid:34424905:4", "asset:table:pmid:34424905:5"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_mann_whitney", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD026906"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:33:49Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 51089, "completion_tokens": 893, "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:34424905", "type": "paper", "label": "pmid:34424905"}, {"id": "source:pmid:34424905", "type": "manuscript", "label": "PMID 34424905 full text"}, {"id": "data:geo:PXD026906", "type": "dataset", "label": "GEO PXD026906"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34424905", "type": "paper", "label": "pmid:34424905"}, {"id": "source:pmid:34424905", "type": "manuscript", "label": "PMID 34424905 full text"}, {"id": "data:geo:PXD026906", "type": "dataset", "label": "GEO PXD026906"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34424905", "type": "extraction", "used": ["source:pmid:34424905"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD026906", "type": "accession_resolution", "used": ["data:geo:PXD026906"], "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:34424905", "parent_hash": "sha256:1716a9b20c2037dc8f62bbc0ce2ead1d9b23bad7c0059babcd3b5fb74d432f02", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:PXD026906 licence not read", "asset:data:geo:PXD026906 not downloaded", "execution.not_run", "method.group_comparison_mann_whitney", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_mann_whitney"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Mann-Whitney"], "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":"2026-11-04T02:38:41+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}}}