{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29069483", "kind": "science-record", "revision": 8, "content_hash": "sha256:d8d37d96233e3cbb30b9418be656b95ac10de18102a0dd4875bc42f3c2e28788", "created_at": "2026-11-01T15:40:29Z", "updated_at": "2026-11-01T22:43:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Protein profile of mouse ovarian follicles grown in vitro.", "doi": "10.1093/molehr/gax056", "pmid": "29069483", "authors": ["Amandine Anastácio", "Kenny A Rodriguez-Wallberg", "Solenne Chardonnet", "Cédric Pionneau", "Christian Fédérici", "Teresa Almeida Santos", "Catherine Poirot"], "journal": "Molecular human reproduction", "year": 2017, "abstract": "STUDY QUESTION: Could the follicle proteome be mapped by identifying specific proteins that are common or differ between three developmental stages from the secondary follicle (SF) to the antrum-like stage?\nSUMMARY ANSWER: From a total of 1401 proteins identified in the follicles, 609 were common to the three developmental stages investigated and 444 were found uniquely at one of the stages.\nWHAT IS KNOWN ALREADY: The importance of the follicle as a functional structure has been recognized; however, up-to-date the proteome of the whole follicle has not been described. A few studies using proteomics have previously reported on either isolated fully-grown oocytes before or after meiosis resumption or cumulus cells.\nSTUDY DESIGN, SIZE, DURATION: The experimental design included a validated mice model for isolation and individual culture of SFs. The system was chosen as it allows continuous evaluation of follicle growth and selection of follicles for analysis at pre-determined developmental stages: SF, complete Slavjanski membrane rupture (SMR) and antrum-like cavity (AF). The experiments were repeated 13 times independently to acquire the material that was analyzed by proteomics.\nPARTICIPANTS/MATERIALS, SETTING, METHODS: SFs (n = 2166) were isolated from B6CBA/F1 female mice (n = 42), 12 days old, from 15 l. About half of the follicles isolated as SF were analyzed as such (n = 1143) and pooled to obtain 139 μg of extracted protein. Both SMR (n = 359) and AF (n = 124) were obtained after individual culture of 1023 follicles in a microdrop system under oil, selected for analysis and pooled, to obtain 339 μg and 170 μg of protein, respectively. The follicle proteome was analyzed combining isoelectric focusing (IEF) fractionation with 1D and 2D LC-MS/MS analysis to enhance protein identification. The three protein lists were submitted to the 'Compare gene list' tool in the PANTHER website to gain insights on the Gene Ontology Biological processes present and to Ingenuity Pathway Analysis to highlight protein networks. A label-free quantification was performed with 1D LC-MS/MS analyses to emphasize proteins with different expression profiles between the three follicular stages. Supplementary western blot analysis (using new biological replicates) was performed to confirm the expression variations of three proteins during follicle development in vitro.\nMAIN RESULTS AND THE ROLE OF CHANCE: It was found that 609 out of 1401 identified proteins were common to the three follicle developmental stages investigated. Some proteins were identified uniquely at one stage: 71 of the 775 identified proteins in SF, 181 of 1092 in SMR and 192 of 1100 in AF. Additional qualitative and quantitative analysis highlighted 44 biological processes over-represented in our samples compared to the Mus musculus gene database. In particular, it was possible to identify proteins implicated in the cell cycle, calcium ion binding and glycolysis, with specific expressions and abundance, throughout in vitro follicle development.\nLARGE SCALE DATA: Data are available via ProteomeXchange with identifier PXD006227.\nLIMITATIONS, REASONS FOR CAUTION: The proteome analyses described in this study were performed after in vitro development. Despite fractionation of the samples before LC-MS/MS, proteomic approaches are not exhaustive, thus proteins that are not identified in a group are not necessarily absent from that group, although they are likely to be less abundant.\nWIDER IMPLICATIONS OF THE FINDINGS: This study allowed a general view of proteins implicated in follicle development in vitro and it represents the most complete catalog of the whole follicle proteome available so far. Not only were well known proteins of the oocyte identified but also proteins that are probably expressed only in granulosa cells.\nSTUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Portuguese Foundation for Science and Technology, FCT (PhD fellowship SFRH/BD/65299/2009 to A.A.), the Swedish Childhood Cancer Foundation (PR 2014-0144 to K.A.R-.W.) and Stockholm County Council to K.A.R-.W. The authors of the study have no conflict of interest to report.", "claims": [{"id": "claim-method", "statement": "Only proteins with a fold-change >2 between the groups (ANOVA P-value < 0.05), and with at least two peptides with significant changes (ANOVA q-value < 0.05 and fold-change >2), were accepted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29069483", "locator": "sections[13] \"Label-free quantification\" paragraph 3", "quote": "Only proteins with a fold-change >2 between the groups (ANOVA P-value < 0.05), and with at least two peptides with significant changes (ANOVA q-value < 0.05 and fold-change >2), were accepted."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available via ProteomeXchange with identifier PXD006227.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29069483", "locator": "sections[0] \"Abstract\" paragraph 7", "quote": "Data are available via ProteomeXchange with identifier PXD006227."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used label-free quantification with 1D LC-MS/MS to assess stage-specific protein abundance, and the source data are available through ProteomeXchange under identifier PXD006227.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29069483", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "A label-free quantification was performed with 1D LC-MS/MS analyses to emphasize proteins with different expression profiles between the three follicular stages."}, {"asset": "source:pmid:29069483", "locator": "sections[0] \"Abstract\" paragraph 7", "quote": "Data are available via ProteomeXchange with identifier PXD006227."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper used label-free quantification with 1D LC-MS/MS to assess stage-specific protein abundance, and the source data are available through ProteomeXchange under identifier PXD006227.", "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:29069483"], "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. 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expressed in the three stages.", "structure": {"pmcid": "PMC5909860", "section_index": 20, "section_title": "Analysis of protein-abundance in the three developmental stages", "row_count": 58, "column_count": 9}, "table": {"label": "Table I", "caption": "Proteins differently expressed in the three stages.", "rows": [["Accession number", "Protein name", "Gene name", "Protein score", "ANOVA P-value", "Fold-change", "Max.", "Min.", "Profile Type (Fig. 7)"], ["Q8K3V4", "Protein-arginine deiminase type-6", "Padi6", "1103.2", "1.9E-07", "3.6", "SF", "AF", "P1"], ["P16125", "L-lactate dehydrogenase B chain", "Ldhb", "879.7", "7.0E-06", "4.9", "SF", "AF", "P1"], ["F8WIV2", "Protein Serpinb6a", "Serpinb6a", "648.1", "3.4E-07", "2.4", "SF", "AF", "P1"], ["Q9CWU5", "KH domain-containing protein 3", "Khdc3", "569.8", "5.9E-05", "3.2", "SF", "SMR/AF", "P1"], ["Q9R0P9", "Ubiquitin carboxyl-terminal hydrolase isozyme L1", "Uchl1", "509.7", "6.9E-05", "4.4", "SF", "AF", "P1"], ["P24549", "Retinal dehydrogenase 1", "Aldh1a1", "418.6", "8.0E-04", "2.0", "SF", "SMR", "P1"], ["P10761", "Zona pellucida sperm-binding protein 3", "Zp3", "346.3", "7.2E-05", "4.9", "SF", "AF", "P1"], ["P54869", "Hydroxymethylglutaryl-CoA synthase, mitochondrial", "Hmgcs2", "335.2", "1.0E-02", "2.1", "SF", "SMR", "P1"], ["Q9DAW9", "Calponin-3", "Cnn3", "308.2", "2.3E-04", "2.5", "SF", "AF", "P1"], ["Q9WVB3", "Transducin-like enhancer protein 6", "Tle6", "239.0", "1.9E-06", "3.5", "SF", "AF", "P1"], ["P10518", "Delta-aminolevulinic acid dehydratase", "Alad", "230.6", "2.0E-04", "2.7", "SF", "AF", "P1"], ["P20239", "Zona pellucida sperm-binding protein 2", "Zp2", "189.8", "7.0E-05", "2.6", "SF", "AF", "P1"], ["Q08EC7", "Pla2g4c protein", "Pla2g4c", "188.0", "2.4E-04", "3.1", "SF", "AF", "P1"], ["P24472", "Glutathione S-transferase A4", "Gsta4", "153.6", "3.3E-04", "2.7", "SF", "SMR", "P1"], ["Q9CWE6", "Oocyte-expressed protein homolog", "Ooep", "94.9", "2.0E-02", "4.8", "SF", "SMR/AF", "P1"], ["P14211", "Calreticulin", "Calr", "276.5", "1.3E-05", "4.6", "SMR", "SF", "P2"], ["Q60817", "Nascent polypeptide-associated complex subunit alpha", "Naca", "270.9", "1.6E-04", "2.3", "SMR", "AF", "P2"], ["Q60605", "Myosin light polypeptide 6", "Myl6", "174.3", "1.6E-03", "3.4", "SMR", "SF/AF", "P2"], ["G3UWR0", "Calumenin", "Calu", "161.2", "5.1E-05", "3.1", "SMR", "SF", "P2"], ["Q4VAA2", "Protein CDV3", "Cdv3", "106.5", "2.1E-04", "2.5", "SMR", "AF", "P2"], ["P20029", "78 kDa glucose-regulated protein", "Hspa5", "2951.4", "2.6E-05", "2.7", "AF", "SF", "P3"], ["P17182", "Alpha-enolase", "Eno1", "1548.7", "4.5E-07", "5.0", "AF", "SF", "P3"], ["P05213", "Tubulin alpha-1B chain", "Tuba1b", "1527.4", "7.0E-04", "2.7", "AF", "SF", "P3"], ["P09103", "Protein disulfide-isomerase", "P4hb", "1416.4", "4.3E-06", "2.7", "AF", "SF", "P3"], ["P16858", "Glyceraldehyde-3-phosphate dehydrogenase", "Gapdh", "701.4", "1.6E-07", "4.0", "AF", "SF", "P3"], ["P14152", "Malate dehydrogenase, cytoplasmic", "Mdh1", 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"Ras-related protein Rab-2A", "Rab2a", "330.6", "3.3E-03", "2.0", "AF", "SF", "P3"], ["Q9DBJ1", "Phosphoglycerate mutase 1", "Pgam1", "329.4", "6.5E-04", "2.2", "AF", "SF", "P3"], ["P17742", "Peptidyl-prolyl cis-trans isomerase A", "Ppia", "325.5", "5.8E-03", "2.2", "SMR", "SF", "P3"], ["P09411", "Phosphoglycerate kinase 1", "Pgk1", "300.5", "2.8E-03", "2.7", "AF", "SF", "P3"], ["Q60715", "Prolyl 4-hydroxylase subunit alpha-1", "P4ha1", "271.1", "7.0E-05", "2.2", "AF", "SF", "P3"], ["Q9QXT0", "Protein canopy homolog 2", "Cnpy2", "254.6", "3.8E-03", "2.3", "SMR", "SF", "P3"], ["A2A7Q5", "Prolyl 3-hydroxylase 1", "Lepre1", "225.9", "2.7E-03", "2.3", "AF", "SF", "P3"], ["G5E850", "Cytochrome b-5, isoform CRA_a", "Cyb5", "222.6", "4.9E-05", "3.4", "AF", "SF", "P3"], ["Q3U4W8", "Ubiquitin carboxyl-terminal hydrolase", "Usp5", "216.6", "5.5E-03", "2.2", "AF", "SF", "P3"], ["G3XA14", "Protein Akr1cl", "Akr1cl", "212.7", "7.5E-03", "3.4", "SMR", "SF", "P3"], ["P34884", "Macrophage migration inhibitory factor", "Mif", "210.1", "1.6E-05", "2.1", "AF", "SF", "P3"], ["P22935", "Cellular retinoic acid-binding protein 2", "Crabp2", "130.9", "2.2E-04", "2.6", "AF", "SF", "P3"], ["Q9CYA0", "Cysteine-rich with EGF-like domain protein 2", "Creld2", "107.5", "2.0E-02", "2.9", "AF", "SF", "P3"], ["P63158", "High-mobility group protein B1", "Hmgb1", "267.9", "2.0E-03", "2.5", "SF", "SMR", "P4"], ["Q9JKB1", "Ubiquitin carboxyl-terminal hydrolase isozyme L3", "Uchl3", "226.8", "1.1E-03", "2.6", "SF", "SMR", "P4"], ["Q9ERD7", "Tubulin beta-3 chain", "Tubb3", "1342.8", "1.6E-03", "3.3", "AF", "SMR", "P5"], ["P31324", "cAMP-dependent protein kinase type II-beta regulatory subunit", "Prkar2b", "1129.2", "1.7E-04", "3.7", "AF", "SF", "P5"], ["Q05816", "Fatty acid-binding protein, epidermal", "Fabp5", "781.9", "9.1E-05", "3.1", "AF", "SF", "P5"], ["P17751", "Triosephosphate isomerase", "Tpi1", "627.6", "5.7E-05", "2.3", "AF", "SF", "P5"], ["Q9D0F9", "Phosphoglucomutase-1", "Pgm1", "403.2", "1.2E-04", "2.3", "AF", "SF/SMR", "P5"], ["Q99JF5", "Diphosphomevalonate decarboxylase", "Mvd", "161.0", "9.7E-05", "3.6", "AF", "SF", "P5"], ["Q62159", "Rho-related GTP-binding protein RhoC", "Rhoc", "136.3", "2.1E-04", "2.4", "AF", "SMR", "P5"]], "row_count": 58, "column_count": 9, "numeric_cells": 241, "header_rows": 1, "locator": "section[20]/table-wrap[1]#gax056TB1"}}, {"id": "asset:table:pmid:29069483:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e9ea741d8db6f6bd85afce27d606bec4a23cfc054a01850794c34ee66ba4c6de", "bytes": 5594, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#gax056TB1", "version": null, "note": "Proteins differently expressed in the three stages.", "structure": {"pmcid": "PMC5909860", "section_index": 23, "section_title": "Analysis of protein-abundance in the three developmental stages", "row_count": 58, "column_count": 9}, "table": {"label": "Table I", "caption": "Proteins differently expressed in the three stages.", "rows": [["Accession number", "Protein name", "Gene name", "Protein score", "ANOVA P-value", "Fold-change", "Max.", "Min.", "Profile Type (Fig. 7)"], ["Q8K3V4", "Protein-arginine deiminase type-6", "Padi6", "1103.2", "1.9E-07", "3.6", "SF", "AF", "P1"], ["P16125", "L-lactate dehydrogenase B chain", "Ldhb", "879.7", "7.0E-06", "4.9", "SF", "AF", "P1"], ["F8WIV2", "Protein Serpinb6a", "Serpinb6a", "648.1", "3.4E-07", "2.4", "SF", "AF", "P1"], ["Q9CWU5", "KH domain-containing protein 3", "Khdc3", "569.8", "5.9E-05", "3.2", "SF", "SMR/AF", "P1"], ["Q9R0P9", "Ubiquitin carboxyl-terminal hydrolase isozyme L1", "Uchl1", "509.7", "6.9E-05", "4.4", "SF", "AF", "P1"], ["P24549", "Retinal dehydrogenase 1", "Aldh1a1", "418.6", "8.0E-04", "2.0", "SF", "SMR", "P1"], ["P10761", "Zona pellucida sperm-binding protein 3", "Zp3", "346.3", "7.2E-05", "4.9", "SF", "AF", "P1"], ["P54869", "Hydroxymethylglutaryl-CoA synthase, mitochondrial", "Hmgcs2", "335.2", "1.0E-02", "2.1", "SF", "SMR", "P1"], ["Q9DAW9", "Calponin-3", "Cnn3", "308.2", "2.3E-04", "2.5", "SF", "AF", "P1"], ["Q9WVB3", "Transducin-like enhancer protein 6", "Tle6", "239.0", "1.9E-06", "3.5", "SF", "AF", "P1"], ["P10518", "Delta-aminolevulinic acid dehydratase", "Alad", "230.6", "2.0E-04", "2.7", "SF", "AF", "P1"], ["P20239", "Zona pellucida sperm-binding protein 2", "Zp2", "189.8", "7.0E-05", "2.6", "SF", "AF", "P1"], ["Q08EC7", "Pla2g4c protein", "Pla2g4c", "188.0", "2.4E-04", "3.1", "SF", "AF", "P1"], ["P24472", "Glutathione S-transferase A4", "Gsta4", "153.6", "3.3E-04", "2.7", "SF", "SMR", "P1"], ["Q9CWE6", "Oocyte-expressed protein homolog", "Ooep", "94.9", "2.0E-02", "4.8", "SF", "SMR/AF", "P1"], ["P14211", "Calreticulin", "Calr", "276.5", "1.3E-05", "4.6", "SMR", "SF", "P2"], ["Q60817", "Nascent polypeptide-associated complex subunit alpha", "Naca", "270.9", "1.6E-04", "2.3", "SMR", "AF", "P2"], ["Q60605", "Myosin light polypeptide 6", "Myl6", "174.3", "1.6E-03", "3.4", "SMR", "SF/AF", "P2"], ["G3UWR0", "Calumenin", "Calu", "161.2", "5.1E-05", "3.1", "SMR", "SF", "P2"], ["Q4VAA2", "Protein CDV3", "Cdv3", "106.5", "2.1E-04", "2.5", "SMR", "AF", "P2"], ["P20029", "78 kDa glucose-regulated protein", "Hspa5", "2951.4", "2.6E-05", "2.7", "AF", "SF", "P3"], ["P17182", "Alpha-enolase", "Eno1", "1548.7", "4.5E-07", "5.0", "AF", "SF", "P3"], ["P05213", "Tubulin alpha-1B chain", "Tuba1b", "1527.4", "7.0E-04", "2.7", "AF", "SF", "P3"], ["P09103", "Protein disulfide-isomerase", "P4hb", "1416.4", "4.3E-06", "2.7", "AF", "SF", "P3"], ["P16858", "Glyceraldehyde-3-phosphate dehydrogenase", "Gapdh", "701.4", "1.6E-07", "4.0", "AF", "SF", "P3"], ["P14152", "Malate dehydrogenase, cytoplasmic", "Mdh1", "462.0", "4.8E-06", "2.1", "AF", "SF", "P3"], ["P48036", "Annexin A5", "Anxa5", "445.8", "5.5E-04", "2.0", "AF", "SF", "P3"], ["Q99KV1", "DnaJ homolog subfamily B member 11", "Dnajb11", "420.4", "1.1E-03", "2.2", "AF", "SF", "P3"], ["G5E8N5", "L-lactate dehydrogenase", "Ldha", "412.5", "3.1E-06", "3.4", "AF", "SF", "P3"], ["P24815", "3 beta-hydroxysteroid dehydrogenase/Delta 5-- > 4-isomerase type 1", "Hsd3b1", "394.6", "6.4E-03", "3.1", "AF", "SF", "P3"], ["E9PXX7", "Thioredoxin domain-containing protein 5", "Txndc5", "380.2", "4.7E-03", "2.1", "AF", "SF", "P3"], ["P57759", "Endoplasmic reticulum resident protein 29", "Erp29", "361.6", "3.1E-05", "2.5", "AF", "SF", "P3"], ["O08807", "Peroxiredoxin-4", "Prdx4", "358.2", "4.0E-05", "2.2", "AF", "SF", "P3"], ["P29758", "Ornithine aminotransferase, mitochondrial", "Oat", "354.1", "5.3E-04", "2.1", "AF", "SF", "P3"], ["P51656", "Estradiol 17-beta-dehydrogenase 1", "Hsd17b1", "351.2", "3.6E-03", "2.4", "AF", "SF", "P3"], ["P53994", "Ras-related protein Rab-2A", "Rab2a", "330.6", "3.3E-03", "2.0", "AF", "SF", "P3"], ["Q9DBJ1", "Phosphoglycerate mutase 1", "Pgam1", "329.4", "6.5E-04", "2.2", "AF", "SF", "P3"], ["P17742", "Peptidyl-prolyl cis-trans isomerase A", "Ppia", "325.5", "5.8E-03", "2.2", "SMR", "SF", "P3"], ["P09411", "Phosphoglycerate kinase 1", "Pgk1", "300.5", "2.8E-03", "2.7", "AF", "SF", "P3"], ["Q60715", "Prolyl 4-hydroxylase subunit alpha-1", "P4ha1", "271.1", "7.0E-05", "2.2", "AF", "SF", "P3"], ["Q9QXT0", "Protein canopy homolog 2", "Cnpy2", "254.6", "3.8E-03", "2.3", "SMR", "SF", "P3"], ["A2A7Q5", "Prolyl 3-hydroxylase 1", "Lepre1", "225.9", "2.7E-03", "2.3", "AF", "SF", "P3"], ["G5E850", "Cytochrome b-5, isoform CRA_a", "Cyb5", "222.6", "4.9E-05", "3.4", "AF", "SF", "P3"], ["Q3U4W8", "Ubiquitin carboxyl-terminal hydrolase", "Usp5", "216.6", "5.5E-03", "2.2", "AF", "SF", "P3"], ["G3XA14", "Protein Akr1cl", "Akr1cl", "212.7", "7.5E-03", "3.4", "SMR", "SF", "P3"], ["P34884", "Macrophage migration inhibitory factor", "Mif", "210.1", "1.6E-05", "2.1", "AF", "SF", "P3"], ["P22935", "Cellular retinoic acid-binding protein 2", "Crabp2", "130.9", "2.2E-04", "2.6", "AF", "SF", "P3"], ["Q9CYA0", "Cysteine-rich with EGF-like domain protein 2", "Creld2", "107.5", "2.0E-02", "2.9", "AF", "SF", "P3"], ["P63158", "High-mobility group protein B1", "Hmgb1", "267.9", "2.0E-03", "2.5", "SF", "SMR", "P4"], ["Q9JKB1", "Ubiquitin carboxyl-terminal hydrolase isozyme L3", "Uchl3", "226.8", "1.1E-03", "2.6", "SF", "SMR", "P4"], ["Q9ERD7", "Tubulin beta-3 chain", "Tubb3", "1342.8", "1.6E-03", "3.3", "AF", "SMR", "P5"], ["P31324", "cAMP-dependent protein kinase type II-beta regulatory subunit", "Prkar2b", "1129.2", "1.7E-04", "3.7", "AF", "SF", "P5"], ["Q05816", "Fatty acid-binding protein, epidermal", "Fabp5", "781.9", "9.1E-05", "3.1", "AF", "SF", "P5"], ["P17751", "Triosephosphate isomerase", "Tpi1", "627.6", "5.7E-05", "2.3", "AF", "SF", "P5"], ["Q9D0F9", "Phosphoglucomutase-1", "Pgm1", "403.2", "1.2E-04", "2.3", "AF", "SF/SMR", "P5"], ["Q99JF5", "Diphosphomevalonate decarboxylase", "Mvd", "161.0", "9.7E-05", "3.6", "AF", "SF", "P5"], ["Q62159", "Rho-related GTP-binding protein RhoC", "Rhoc", "136.3", "2.1E-04", "2.4", "AF", "SMR", "P5"]], "row_count": 58, "column_count": 9, "numeric_cells": 241, "header_rows": 1, "locator": "section[20]/table-wrap[1]#gax056TB1"}}], "gaps": ["asset:data:geo:PXD006227 not downloaded", "asset:data:geo:PXD006227 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Only proteins with a fold-change >2 between the groups (ANOVA P-value < 0.05), and with at least two peptides with significant changes (ANOVA q-value < 0.05 and fold-change >2), were accepted."}}], "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "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": ["PXD006227"], "resolved_accessions": ["PXD006227"], "statements": ["Data are available via ProteomeXchange with identifier PXD006227."], "basis": "The paper names PXD006227 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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:29069483", "data:geo:PXD006227", "asset:table:pmid:29069483:1", "asset:table:pmid:29069483:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD006227"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:40Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 8, "usage": {"prompt_tokens": 113148, "completion_tokens": 2966, "cached_tokens": 29208}}, "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:29069483", "type": "paper", "label": "pmid:29069483"}, {"id": "source:pmid:29069483", "type": "manuscript", "label": "PMID 29069483 full text"}, {"id": "data:geo:PXD006227", "type": "dataset", "label": "GEO PXD006227"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29069483", "type": "paper", "label": "pmid:29069483"}, {"id": "source:pmid:29069483", "type": "manuscript", "label": "PMID 29069483 full text"}, {"id": "data:geo:PXD006227", "type": "dataset", "label": "GEO PXD006227"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29069483", "type": "extraction", "used": ["source:pmid:29069483"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD006227", "type": "accession_resolution", "used": ["data:geo:PXD006227"], "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:29069483", "parent_hash": "sha256:ebfaf49b90de57f161d879027feffbd7b53b703ac6bffe64390969d84a5eaef9", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:PXD006227 licence not read", "asset:data:geo:PXD006227 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["Protein profile of mouse ovarian follicles grown in vitro.", "cretion, and it is the main source of ATP in mouse preantral follicles in vitro (Boland et al.,"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"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": ["focusing (IEF) fractionation with 1D and 2D LC-MS/MS analysis to enhance protein identification.", "el-free quantification was performed with 1D LC-MS/MS analyses to emphasize proteins with differen", "Despite fractionation of the samples before LC-MS/MS, proteomic approaches are not exhaustive, th", "to acquire the material that was analyzed by proteomics. PARTICIPANTS/MATERIALS, SETTING, METHODS: S"], "order_basis": "paper_text_order:1198", "id": "assay:2"}, {"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": ["n the three follicular stages. Supplementary western blot analysis (using new biological replicates) w", "Protein-abundance results were validated by western blot analysis of selected proteins, namely PKAR2B", "d proteins, namely PKAR2B and LDHB (Fig. 9). Western blot demonstrating variable expression of PRKAR2B", "during follicle development is also shown by western blot, with similar abundance in the SMR and AF st"], "order_basis": "paper_text_order:2237", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Only proteins with a fold-change >2 between the groups (ANOVA P-value < 0.05), and with at least two peptides with significant changes (ANOVA q-value < 0.05 and fold-change >2), were accepted."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]},"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":"2026-11-04T00:41:07+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}}}