{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:25659148", "kind": "science-record", "revision": 7, "content_hash": "sha256:d625607a64fd40b29f49c974609f324d9a309801811618f635eaff39464063bc", "created_at": "2026-11-01T15:40:07Z", "updated_at": "2026-11-01T21:58:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of synaptosomal proteins binding to monomeric and oligomeric α-synuclein.", "doi": "10.1371/journal.pone.0116473", "pmid": "25659148", "authors": ["Cristine Betzer", "A James Movius", "Min Shi", "Wei-Ping Gai", "Jing Zhang", "Poul Henning Jensen"], "journal": "PloS one", "year": 2015, "abstract": "Monomeric α-synuclein (αSN) species are abundant in nerve terminals where they are hypothesized to play a physiological role related to synaptic vesicle turn-over. In Parkinson's disease (PD) and dementia with Lewy body (DLB), αSN accumulates as aggregated soluble oligomers in terminals, axons and the somatodendritic compartment and insoluble filaments in Lewy inclusions and Lewy neurites. The autosomal dominant heritability associated to mutations in the αSN gene suggest a gain of function associated to aggregated αSN. We have conducted a proteomic screen to identify the αSN interactome in brain synaptosomes. Porcine brain synaptosomes were fractionated, solubilized in non-denaturing detergent and subjected to co-immunoprecipitation using purified recombinant human αSN monomers or oligomers as bait. The isolated αSN binding proteins were identified with LC-LTQ-orbitrap tandem mass spectrometry and quantified by peak area using Windows client application, Skyline Targeted Proteomic Environment. Data are available via ProteomeXchange with identifier PXD001462. To quantify the preferential binding an average fold increase was calculated by comparing binding to monomer and oligomer. We identified 10 proteins preferentially binding monomer, and 76 binding preferentially to oligomer and a group of 92 proteins not displaying any preferred conformation of αSN. The proteomic data were validated by immunoprecipitation in both human and porcine brain extracts using antibodies against monomer αSN interactors: Abl interactor 1, and myelin proteolipid protein, and oligomer interactors: glutamate decarboxylase 2, synapsin 1, glial fibrillary acidic protein, and VAMP-2. We demonstrate the existence of αSN conformation selective ligands and present lists of proteins, whose identity and functions will be useful for modeling normal and pathological αSN dependent processes.", "claims": [{"id": "claim-method", "statement": "In order for a protein to be considered as either monomer or oligomer binding Student’s t-test was applied and conventional significance of 95% was accepted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25659148", "locator": "sections[8] \"Semi-quantitative identification of proteins based on mass spectrometric peptide mapping\" paragraph 2", "quote": "In order for a protein to be considered as either monomer or oligomer binding Student’s t-test was applied and conventional significance of 95% was accepted."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD001462. Additional relevant data are within the paper and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25659148", "locator": "sections[16] \"Data Availability\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD001462. Additional relevant data are within the paper and its Supporting Information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used Student’s t-test with conventional 95% significance and a ≥2-fold average increase criterion to classify preferential αSN binding; the underlying mass-spectrometry data are available through ProteomeXchange/PRIDE under identifier PXD001462.", "kind": "quantitative", "target": {"value": 2.0, "unit": "fold change", "tolerance": null, "source": "The criteria of ≥ 2-fold increase in average fold increase has to be fulfilled in order to be considered as preferential binding protein, similar to the criteria set up in the phospho-peptide interaction study by McFarland et al. [35]."}, "evidence": [{"asset": "source:pmid:25659148", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We demonstrate the existence of αSN conformation selective ligands and present lists of proteins, whose identity and functions will be useful for modeling normal and pathological αSN dependent processes."}, {"asset": "source:pmid:25659148", "locator": "sections[8] \"Semi-quantitative identification of proteins based on mass spectrometric peptide mapping\" paragraph 2", "quote": "In order for a protein to be considered as either monomer or oligomer binding Student’s t-test was applied and conventional significance of 95% was accepted."}, {"asset": "source:pmid:25659148", "locator": "sections[8] \"Semi-quantitative identification of proteins based on mass spectrometric peptide mapping\" paragraph 2", "quote": "The criteria of ≥ 2-fold increase in average fold increase has to be fulfilled in order to be considered as preferential binding protein, similar to the criteria set up in the phospho-peptide interaction study by McFarland et al. [35]."}, {"asset": "source:pmid:25659148", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Data are available via ProteomeXchange with identifier PXD001462."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper used Student’s t-test with conventional 95% significance and a ≥2-fold average increase criterion to classify preferential αSN binding; the underlying mass-spectrometry data are available through ProteomeXchange/PRIDE under identifier PXD001462.", "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:25659148"], "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:PXD001462"], "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:student_t", "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:PXD001462"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:25659148", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0116473", "sha256": "sha256:50a83e24efe28dc4ef5d7c4ae22d16383daf786c3dd8aded878a1e21cf4eee2b", "bytes": 70762, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0116473", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC4319895", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD001462", "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=PXD001462", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD001462", "version": null, "note": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD001462. Additional relevant data are within the paper and its Supporting Information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD001462. Additional relevant data are within the paper 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": "Identification of Alpha-Synuclein Interacting Synaptosomal Proteins", "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:25659148:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:22742f47ff58c10d2d2c0e123466f7550d07de74a7cd8bfe01579cd114d98bde", "bytes": 1039, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#pone.0116473.t001", "version": null, "note": "Preferential αSN monomer interacting proteins.", "structure": {"pmcid": "PMC4319895", "section_index": 8, "section_title": "Semi-quantitative identification of proteins based on mass spectrometric peptide mapping", "row_count": 15, "column_count": 5}, "table": {"label": "Table 1", "caption": "Preferential αSN monomer interacting proteins.", "rows": [["Protein", "UniProt/ swiss-Prot", "Synapto-somal fraction", "Fold increase", "p-value"], ["Mitochondria"], ["Cytochrome b-c1 complex subunit 2", "F1RPD2_PIG", "LP2", "16", "<0.03"], ["Stomatin protein 2", "F1SIH5_PIG", "LP1", "5", "0.02"], ["GABA aminotransferase(4-aminobutyrate aminotransferase)", "GABT_PIG", "LP1", "23", "<0.01"], ["Fumarylacetoacetate hydrolase domain-containing protein 2", "F1SU52_PIG", "LP1", "6", "<0.01"], ["Plasma membrane"], ["Myelin proteolipid protein*", "MYPR_PIG", "LS1", "3", "0.03"], ["Cytoplasm"], ["Abl interactor 1*", "F1RTW7_PIG", "LP2", "2", "<0.01"], ["Phosphatidylethanolamine-binding protein 1", "F1RKG8_PIG", "LP1", "16", "<0.01"], ["TNF receptor-associated protein 1", "F1RK45_PIG", "LP1", "6", "0.02"], ["Tropomodulin-2", "F1RZB5_PIG", "LP2", "8", "0.01"], ["Vesicle"], ["V-type proton ATPase subunit F", "F1SMN6_PIG", "LP1", "9", "<0.01"]], "row_count": 15, "column_count": 5, "numeric_cells": 30, "header_rows": 1, "locator": "section[8]/table-wrap[1]#pone.0116473.t001"}}, {"id": "asset:table:pmid:25659148:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:de6903ca415e0c6f845341cc9ce30e36fca4845c9d3b632e22cc102c40a8a3a1", "bytes": 5276, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[2]#pone.0116473.t002", "version": null, "note": "αSN oligomer interacting proteins.", "structure": {"pmcid": "PMC4319895", "section_index": 8, "section_title": "Semi-quantitative identification of proteins based on mass spectrometric peptide mapping", "row_count": 48, "column_count": 10}, "table": {"label": "Table 2", "caption": "αSN oligomer interacting proteins.", "rows": [["Protein", "UniProt/ swiss-Prot", "Synapto-somal fraction", "Fold increase", "p-value", "Protein", "UniProt/ swiss-Prot", "Synapto-somal fraction", "Fold increase", "p-value"], ["Mitochondrial"], ["3-hydroxyacyl-CoA dehydrogenase type-2", "F1RUI1_PIG", "LP1", "6", "0.01", "2-oxoglutarate/malate carrier protein", "F1RFX9_PIG", "LP2", "4", "0.05"], ["ADP/ATP translocase 3", "ADT3_PIG", "LS1", "66", "<0.01", "Glutamate carrier 1", "F1RYY8_PIG", "LS1", "49", "<0.01"], ["ATP synthase subunit α", "F1RPS8_PIG", "LS1", "13", "<0.01", "Mitochondrial import inner membrane translocase subunin", "F1SA66_PIG", "LS2", "3", "0.01"], ["Ca2+-binding mitochondrial carrier protein Aralar2", "I3L614_PIG", "LS1", "17", "0.01", "Phosphatidate cytidylyl-transferase 2", "I3LAQ3_PIG", "LS1", "5", "<0.01"], ["Elongation factor Tu", "F1RFI1_PIG", "LP1", "22", "<0.01", "Pyruvate carboxylase", "F1RUV6_PIG", "LS1", "7", "0.01"], ["Heat shock 60 kDa protein 1", "F1SMZ7_PIG", "LS2", "22", "<0.01", "Heat shock 70kDa protein 9 (Mortalin)", "F1RGJ3_PIG", "LS1", "2", "<0.02"], ["LETM1 and EF-hand domain-containing protein 1", "F1S6V4_PIG", "LS2", "60", "<0.01", "Trifunctional enzyme α", "ECHA_PIG", "LS1", "7", "<0.01"], ["Endoplasmic reticulum"], ["78 kDa glucose-regulated protein", "F1RS36_PIG", "LP2, LS2", "3", "0.03", "Hypoxia up regulated protein 1", "F1SAI8_PIG", "LP2", "4", "0.04"], ["Endoplasmin", "ENPL_PIG", "LS1", "4", "0.01", "Reticulocalbin 2", "F1SJ93_PIG", "All", "15", "<0.01"], ["Plasma membrane"], ["Excitatory amino acidtransporter 1", "F1SNA0_PIG", "LS1, LP2", "4", "0.03", "Plasma membrane Ca2+ ATPase 4", "F1S6B3_PIG", "LS1", "6", "<0.01"], ["Excitatory amino acidtransporter 2", "F1SHF9_PIG", "LS1", "7", "<0.01", "Syntaxin-binding protein 1", "F1RS11_PIG", "LS1, LS2", "23", "0.05"], ["", "Transmembrane protein 33", "F1S4G6_PIG", "LS1", "399", "<0.01"], ["Cytoplasm"], ["40S ribosomal protein S3", "RS3_PIG", "LS2", "7", "<0.01", "Dynein 1, light intermediate chain 2", "I3LQU0_PIG", "LS2", "22", "<0.01"], ["40S ribosomal protein S5-like isoform 2", "F2Z5E6_PIG", "LP2", "5", "0.02", "Glial fibrillary acidic protein*", "F1RR02_PIG", "LS1", "3", "<0.01"], ["60S ribosomal protein L32", "RL32_PIG", "LS1", "19", "<0.01", "Glutamate decarboxylase 2*", "DCE2_PIG", "LS2", "38", "<0.01"], ["52 kDa Rho protein", "F1RHN8_PIG", "LS2", "2", "0.03", "Neuronal migration protein doublecortin", "I3L5C8_PIG", "LS1, LS2", "53", "<0.01"], ["α-crystallin B chain", "CRYAB_PIG", "LP2", "3", "0.01", "Rab GDP dissociation inhibitor α", "I3L893_PIG", "LS1", "8", "0.01"], ["Aminoacyl tRNA synthase complex-interacting multifunctional protein 2", "F1RFM7_PIG", "LP2", "10", "0.01", "Ribosomal protein, large, P2", "F1RYZ0_PIG", "LS1", "11", "<0.01"], ["ATP-citrate synthase", "F1S0N1_PIG", "LS2", "58", "0.02", "S100 Ca2+ binding protein A14", "F1SFV3_PIG", "LS1", "3", "0.01"], ["Ca2+-binding protein 1", "F1RJI3_PIG", "LP2", "10", "0.01", "Seryl-tRNA synthetase", "F1S5Z3_PIG", "LS2", "261", "<0.01"], ["cAMP-dependent protein kinase catalytic β", "KAPCB_PIG", "LP2", "5", "0.01", "T-complex protein 1 α", "F1SB63_PIG", "LS2", "373", "<0.01"], ["Chaperonin containing TCP1, subunit 2β", "D0G0C8_PIG", "LS2", "478", "<0.01", "T-complex protein 1 δ", "F1SQN1_PIG", "LS1", "11", "0.01"], ["Dynein 1 intermediate chain 2", "F1S087_PIG", "LS1", "10", "<0.01", "T-complex protein 1 η", "F1SLF6_PIG", "LS1", "133", "0.03"], ["FMR1-interacting protein 2", "F1RQE9_PIG", "LP2", "3", "0.02", "T-complex protein 1 γ", "F1RP17_PIG", "LS1, LS2", "204", "<0.01"], ["Dihydropyrimidinase 2", "I3LJE2_PIG", "LS1, LS2", "23", "<0.01", "14–3–3 protein ζ/δ", "F2Z558_PIG", "LP1", "2", "0.04"], ["Dynein heavy polypeptide", "F1S9Y5_PIG", "LS2, LP2", "802", "<0.01", "14–3–3 protein γ", "F2Z4Z1_PIG", "LP1", "9", "0.03"], ["Nucleus"], ["A-kinase anchor protein 5", "F1SA75_PIG", "LS1", "9", "0.01", "Signal recognition particle 54 kDa protein", "F2Z5M9_PIG", "LS2", "18", "<0.01"], ["Vesicle"], ["Amphiphysin", "I3L8X6_PIG", "LP2", "5", "0.03", "Synaptic vesicle glycoprotein 2A", "F1SDF9_PIG", "LS1", "9", "<0.01"], ["Nipsnap homolog 1", "F1RFF5_PIG", "LP1", "3", "0.03", "Tripeptidyl-peptidase 1", "I3L812_PIG", "LS2", "45", "<0.01"], ["Sorting nexin 6", "F1SHH3_PIG", "LS2", "181", "<0.01", "Vacuolar protein sorting-associated protein 53", "F1RHI3_PIG", "LP2", "31", "<0.01"], ["Synapsin 1*", "B7TY10_PIG", "LS1, LS2, LP2", "9", "0.01", "V-type proton ATPase subunit d 1", "F2Z5H6_PIG", "LP2", "2", "0.03"], ["Cytoskeleton"], ["α-centractin", "F2Z5G5_PIG", "LS2", "20", "0.02", "Spectrin α chain", "F1RR78_PIG", "LS1", "3", "<0.01"], ["α-internexin", "F1S847_PIG", "LS1", "3", "0.02", "Tubulin α-4A chain", "F2Z5S8_PIG", "LS1", "6", "0.01"], ["Dynamin-2", "F1S593_PIG", "LS2", "64", "<0.01", "Tubulin β-3 chain", "F1S6M7_PIG", "LS1, LS2", "15", "0.01"], ["Microtubule-associated protein 6", "F1SUM1_PIG", "LS1, LS2", "28", "<0.01", "Tubulin β-4 chain", "F2Z5K5_PIG", "LS1, LS2, LP2", "9", "0.01"], ["Neurofilament heavy polypeptide", "F1RFH3_PIG", "LP1", "4", "0.02", "Tubulin polymerization-promoting protein", "I3LB30_PIG", "LP1", "3", "0.04"], ["Sirtuin 2", "I3L8A1_PIG", "LS1", "66", "0.01", "", "", "", ""], ["Secreted"], ["Complement C4 precursor", "F1RQW2_PIG", "LS1", "2", "0.01", "C-type natriuretic peptide", "F1S0P3_PIG", "LS1, LP2", "7", "0.05"], ["Complement C5 precursor", "F1SME1_PIG", "LS2", "19", "<0.01", "Tenascin-R", "F1S706_PIG", "LS2", "8", "0.01"]], "row_count": 48, "column_count": 10, "numeric_cells": 222, "header_rows": 1, "locator": "section[8]/table-wrap[2]#pone.0116473.t002"}}, {"id": "asset:table:pmid:25659148:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:efb837ec1432c5db4f0290979c317c992e295610dfd9f5e3d10de9e48adfb000", "bytes": 5665, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[3]#pone.0116473.t003", "version": null, "note": "Non-conformation specific αSN interacting proteins.", "structure": {"pmcid": "PMC4319895", "section_index": 8, "section_title": "Semi-quantitative identification of proteins based on mass spectrometric peptide mapping", "row_count": 57, "column_count": 6}, "table": {"label": "Table 3", "caption": "Non-conformation specific αSN interacting proteins.", "rows": [["Protein", "UniProt/ swiss-Prot", "Synaptosomal", "Protein", "UniProt/ swiss-Prot", "Synaptosomal"], ["Mitochondrial"], ["2-oxoglutarate dehydrogenase", "F1SSH8_PIG", "LP2", "Mitochondrial carrier homolog 2", "F1SIE0_PIG", "LP1"], ["39S ribosomal protein L12", "I3LSY1_PIG", "LP2", "Mitochondrial import inner membrane translocase subunit", "F1RK50_PIG", "LP1"], ["Adenine nucleotide translocator 2", "F2Z565_PIG", "LS1, LP1", "NADH dehydrogenase [ubiquinone] 1 β subcomplex subunit 10-like", "I3LDC3_PIG", "LP1"], ["ATP synthase subunit beta", "F1SLA0_PIG", "LP2", "NADH dehydrogenase [ubiquinone] flavoprotein 1", "F1RVN1_PIG", "LP2"], ["Cytochrome b-c1 complex subunit 8-like isoform 2", "F1RI18_PIG", "LP2", "NADP-dependent malic enzyme", "F1STS4_PIG", "LP1"], ["Cytochrome c oxidase subunit 1", "COX1_PIG", "LP2", "Pentatricopeptide repeat domain 3", "F1SVC4_PIG", "LP2"], ["Chymodenin", "F1RLH7_PIG", "LP2", "Prohibitin 2", "I3LQN4_PIG", "LP1, LP2"], ["Dihydrolipoyllysine-residue acetyltransferase component of pyruvate", "F1SMB2_PIG", "LP1, LP2", "Pyruvate dehydrogenase: subunit beta", "F1SGH5_PIG", "LP2"], ["Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex", "ODO2_PIG", "LP1, LP2", "Short-chain specific acyl-CoA dehydrogenase", "F1RJH2_PIG", "LP1"], ["Glutamate dehydrogenase 1", "DHE3_PIG", "LP1", "Thioredoxin-dependent peroxide reductase", "F1S418_PIG", "LS1"], ["Hexokinase 1", "F1SUF2_PIG", "LP2", "Translocase of outer mitochondrial membrane", "F2Z4X6_PIG", "LP1"], ["Long-chain 3-ketoacyl-CoA thiolase", "F1SDN2_PIG", "LP1", "Voltage-dependent anion-selective channel 1", "VDAC1_PIG", "LP1, LP2"], ["Endoplasmic reticulum"], ["B-cell receptor-associated protein 31", "F1S2A8_PIG", "LP2", "Phospholipase D3", "I3L5D6_PIG", "LP2"], ["Ca2+/calmodulin-dependent protein kinase II γ-B", "Q7JFN4_PIG", "LP2", "Protein disulfide-isomerase A6", "E1CAJ6_PIG", "LP2"], ["NADH dehydrogenase (ubiquinone) Fe-S protein 5, 15 kDa (NADH-coenzyme Q reductase)", "F1SV23_PIG", "LP1, LP2", "Stromal interaction molecule 1 precursor", "F1SUZ4_PIG", "LP2"], ["Plasma membrane"], ["Adaptor-related protein complex 2, mu 1 subunit", "I3LL07_PIG", "LP2", "Immunoglobulin superfamily member 8", "F1RJW5_PIG", "LP2"], ["AP-2 complex subunit β", "I3L6Y6_PIG", "LP2", "Neural cell adhesion molecule 1", "F1SM72_PIG", "LP1, LP2"], ["BPI fold-containing family B member 1", "I3LAK0_PIG", "LP2", "Neurotrimin", "F1S6D0_PIG", "LP2"], ["Brain acid soluble protein 1 isoform 1", "F1SRL9_PIG", "LP1", "Oligodendrocyte-myelin glycoprotein", "F1RJ55_PIG", "LP2"], ["Ca2+/calmodulin-dependent protein kinase II α", "F1RL74_PIG", "LP2", "Paralemmin-1", "PALM_PIG", "LP2"], ["Ca2+ modulating ligand", "F1RHC6_PIG", "LP2", "Plasma membrane Ca2+ ATPase 2", "I3LIE6_PIG", "LP2"], ["Cell adhesion molecule 2", "F1SK66_PIG", "LP2", "Prohibitin", "F2Z543_PIG", "LP2"], ["Cell cycle exit and neuronal differentiation protein 1", "CEND_PIG", "LP1", "Protein RER1", "I3LJC8_PIG", "LP2"], ["Cytolytic trigger molecule G7", "FCGR3_PIG", "LP1", "Protein transport protein Sec61 subunit α2", "F2Z5D0_PIG", "LP2"], ["EH domain-containing protein 3", "F1RQR4_PIG", "LP2", "Thy-1 membrane glycoprotein precursor", "B9ZSM8_PIG", "LP2"], ["Cytoplasm"], ["40S ribosomal protein S3a", "F2Z5C7_PIG", "LP2", "Elongation factor 1-α", "Q0PY11_PIG", "LP2"], ["60S ribosomal protein L6", "RL6_PIG", "LP2", "Elongation factor 1-β", "F1SHD6_PIG", "LP2"], ["60S ribosomal protein L12", "Q6QAS5_PIG", "LP2", "Glutathione transferase ζ 1", "F1S2N0_PIG", "LP1"], ["60S ribosomal protein L22", "RL22_PIG", "LP2", "Heterogeneous nuclear ribonucleoprotein K", "I3LQS0_PIG", "LP2"], ["60S acidic ribosomal protein P1", "F1SIT7_PIG", "LP2", "Proteasome subunit α type-2", "I3LAB6_PIG", "LP2"], ["ABI gene family member 3 isoform 2", "I3LB01_PIG", "LP2", "protein-arginine deiminase type-2", "I3LNE4_PIG", "LP2"], ["AP-1 complex subunit sigma-1A", "Q06AS6_PIG", "LP2", "Ribosomal phosphoprotein large PO subunit", "RLA0_PIG", "LP2"], ["cAMP-dependent protein kinase type II-α regulatory subunit", "KAP2_PIG", "LP1", "Protein kinase C ε type", "F1S5K7_PIG", "LP2"], ["Creatine kinase", "I3LPB5_PIG", "LP1, LP2", "S100 Ca2+ binding protein A16", "F2Z5M4_PIG", "LP2"], ["Cytoplasmic dynein 1 heavy chain 1", "F1S9Y5_PIG", "LS2, LP2", ""], ["Nucleus"], ["Barrier-to-autointegration factor-like isoform 1", "F1RU33_PIG", "LP1", "Nucleosome assembly protein 1", "F1SGD7_PIG", "LP2"], ["Dynein light chain Tctex-type 3", "I3LUI9_PIG", "LP2", "WD repeat-containing protein 61", "F1RKU4_PIG", "LP2"], ["Homeobox prox 1", "F1SFF4_PIG", "LP2", "", "", ""], ["Vesicle"], ["Membrane-associated progesterone receptor component 1", "PGRC1_PIG", "LP2", "Syntaxin-1A", "F1RJM9_PIG", "LP2"], ["Synaptic vesicle glycoprotein 2B", "F1SCI2_PIG", "LP2", "Vacuolar protein sorting-associated protein 45", "F1SDG5_PIG", "LP2"], ["Synaptotagmin-1", "F1RYK1_PIG", "LP2", "V-type proton ATPase subunit D", "F1SA40_PIG", "LP2"], ["", "Vesicle-associated membrane protein-associated protein B", "VAPB_PIG", "LP2"], ["Cytoskeleton"], ["Actin related protein 2/3 complex, subunit 4", "F1SQE6_PIG", "LP2", "Dynamin-1", "F1RRW8_PIG", "LP2"], ["Actin-related protein 2/3 complex subunit 5", "B5APV0_PIG", "LP2", "Erythrocyte membrane protein band 4.1", "F1SM86_PIG", "LP2"], ["Actin-related protein 3", "F2Z5D2_PIG", "LP2", "Microtubule-associated protein 1B", "F1SK12_PIG", "LP1"], ["Adenylyl cyclase-associated protein 1", "I3LVT1_PIG", "LP2", "Microtubule-associated protein 2 isoform 2", "F1SSS6_PIG", "LS1, LP1"], ["Cytoskeleton-associated protein 4", "F1SPP8_PIG", "LP2", "Septin 2", "F1SIP0_PIG", "LS1"], ["Secreted"], ["Granulin", "F1RQZ0_PIG", "LP1, LS2", "", "", ""]], "row_count": 57, "column_count": 6, "numeric_cells": 84, "header_rows": 1, "locator": "section[8]/table-wrap[3]#pone.0116473.t003"}}], "gaps": ["asset:data:geo:PXD001462 not downloaded", "asset:data:geo:PXD001462 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Students t-test"}}, {"id": "method-2", "family": null, "specific": null, "label": "Student’s t-test", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "In order for a protein to be considered as either monomer or oligomer binding Student’s t-test was applied and conventional significance of 95% was accepted."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "student_t", "expected_value": 2.0, "unit": "fold change", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-per-cent", "claim_id": "claim-target-result", "operation": "student_t", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "gaps": ["method.reader_named_unmapped", "method.student_t"]}, "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": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": ["PXD001462"], "resolved_accessions": ["PXD001462"], "statements": ["The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD001462. Additional relevant data are within the paper and its Supporting Information files."], "basis": "The paper names PXD001462 in PRIDE partner repository via the ProteomeXchange Consortium and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:25659148", "data:geo:PXD001462", "asset:table:pmid:25659148:1", "asset:table:pmid:25659148:2", "asset:table:pmid:25659148:3"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD001462"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:23:30Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 8, "usage": {"prompt_tokens": 140533, "completion_tokens": 3027, "cached_tokens": 2088}}, "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:25659148", "type": "paper", "label": "pmid:25659148"}, {"id": "source:pmid:25659148", "type": "manuscript", "label": "PMID 25659148 full text"}, {"id": "data:geo:PXD001462", "type": "dataset", "label": "GEO PXD001462"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:25659148", "type": "paper", "label": "pmid:25659148"}, {"id": "source:pmid:25659148", "type": "manuscript", "label": "PMID 25659148 full text"}, {"id": "data:geo:PXD001462", "type": "dataset", "label": "GEO PXD001462"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-25659148", "type": "extraction", "used": ["source:pmid:25659148"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD001462", "type": "accession_resolution", "used": ["data:geo:PXD001462"], "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:25659148", "parent_hash": "sha256:9112a3bf5de821520cf9ecdf5b4f1314dca69d9680a635048bcd82bcdce3c446", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:PXD001462 licence not read", "asset:data:geo:PXD001462 not downloaded", "execution.not_run", "method.reader_named_unmapped", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "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": ["were identified with LC-LTQ-orbitrap tandem mass spectrometry and quantified by peak area using Windows cl", "iated to aggregated αSN. We have conducted a proteomic screen to identify the αSN interactome in br", "ecision making used in the semi-quantitative mass spectrometric analysis.Brain tissue is prepared and fracti", "ation and analysis by LC-LTQ orbitrap tandem mass spectrometry. Peptides identified in at least two of the"], "order_basis": "paper_text_order:590", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Students t-test"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]},"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":"2026-11-04T02:38:43+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}}}