{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34445296", "kind": "science-record", "revision": 6, "content_hash": "sha256:11130344d5426d88ebba140bbd3e6076a1c000cdcb18751afd333fccecd59e36", "created_at": "2026-11-01T15:41:49Z", "updated_at": "2026-11-01T21:26:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Differential Retinal Protein Expression in Primary and Secondary Retinal Ganglion Cell Degeneration Identified by Integrated SWATH and Target-Based Proteomics.", "doi": "10.3390/ijms22168592", "pmid": "34445296", "authors": ["Jacky M K Kwong", "Joseph Caprioli", "Ying H Sze", "Feng J Yu", "King K Li", "Chi H To", "Thomas C Lam"], "journal": "International journal of molecular sciences", "year": 2021, "abstract": "To investigate the retinal proteins associated with primary and secondary retinal ganglion cell (RGC) degeneration and explore their molecular pathways, SWATH label-free and target-based mass spectrometry was employed to identify the proteomes in various retinal locations in response to localized optic nerve injury. Unilateral partial optic nerve transection (pONT) was performed on adult Wistar rats and their retinas were harvested 2 weeks later. To confirm the separation of primary and secondary RGC degeneration, immunohistochemistry of RNA binding protein with multiple splicing (RBPMS) and glial fibrillary acidic protein (GFAP) was performed on retinal whole-mounts. Retinal proteomes in the temporal and nasal quadrants were evaluated with high resolution hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS), and SWATH-based acquisition, and their expression was compared to the corresponding retinal quadrant in contralateral control eyes and further validated by multiple reaction monitoring mass spectrometry (MRM-MS). A total of 3641 proteins (FDR < 1%) were identified using QTOF-MS. The raw data are available via ProteomeXchange with the identifier PXD026783. Bioinformatics data analysis showed that there were 37 upregulated and 25 downregulated proteins in the temporal quadrant, whereas 20 and five proteins were upregulated and downregulated, respectively, in the nasal quadrant, respectively (n = 4, p < 0.05; fold change ≥ 1.4-fold or ≤0.7). Six proteins were regulated in both the temporal and the nasal quadrants, including CLU, GFAP, GNG5, IRF2BPL, L1CAM, and CPLX1. Linear regression analysis indicated a strong association between the data obtained by means of SWATH-MS and MRM-MS (temporal, R2 = 0.97; nasal, R2 = 0.96). Gene ontology analysis revealed statistically significant changes in the biological processes and cellular components of primary RGC degeneration. The majority of the significant changes in structural, signaling, and cell death proteins were associated with the loss of RGCs in the area of primary RGC degeneration. The combined use of SWATH-MS and MRM-MS methods detects and quantifies regional changes of retinal protein expressions after localized injury. Future investigation with this integrated approach will significantly increase the understanding of diverse processes of progressive RGC degeneration from a proteomic prospective.", "claims": [{"id": "claim-method", "statement": "Samples were normalized by most likely ratio (MLR) normalization with a paired t-test used to detect significantly differentiated proteins in biological samples among experimental groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34445296", "locator": "sections[9] \"4.5. Sciex TripleTOF 6600 Mass Spectrometry and SWATH-MS Acquisition\" paragraph 3", "quote": "Samples were normalized by most likely ratio (MLR) normalization with a paired t-test used to detect significantly differentiated proteins in biological samples among experimental groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented in this study are available in this article and Supplementary Materials section.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34445296", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "The data presented in this study are available in this article and Supplementary Materials section."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34445296"], "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:PXD026783"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"r_squared": "S and MRM-MS (temporal, R2 = 0"}, "inputs": ["data:geo:PXD026783"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34445296", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/ijms22168592", "sha256": "sha256:2356d71b000fc6056c061806a9b8586557eab2c67e5c5f87edbfd76056b0a4d4", "bytes": 64844, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/ijms22168592", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8395271", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD026783", "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=PXD026783", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD026783", "version": null, "note": "The data presented in this study are available in this article and Supplementary Materials section.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data presented in this study are available in this article and Supplementary Materials section.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Differential retinal protein expression in primary and secondary retinal ganglion cell degeneration identified by integrated SWATH and target-based proteomics", "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:34445296:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c889c2beb85e1eca2140866eae8ee5edc334f91e835902977d68394f9312861c", "bytes": 432, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[2]/table-wrap[1]#ijms-22-08592-t001", "version": null, "note": "Protein and peptide identification in retinal samples 2 weeks after pONT.", "structure": {"pmcid": "PMC8395271", "section_index": 2, "section_title": "2. Results", "row_count": 4, "column_count": 7}, "table": {"label": "Table 1", "caption": "Protein and peptide identification in retinal samples 2 weeks after pONT.", "rows": [["", "Sample Number", "Pooled Sample *", "MarkerView **"], ["", "1", "2", "3", "4"], ["Protein", "3560", "3270", "3504", "3587", "3641", "3173"], ["Peptide", "24,310", "20,800", "23,569", "25,080", "25,313", "18,336"]], "row_count": 4, "column_count": 7, "numeric_cells": 16, "header_rows": 2, "locator": "section[2]/table-wrap[1]#ijms-22-08592-t001"}}, {"id": "asset:table:pmid:34445296:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:83c8967f52b93500929893ac5f48679510f5453f298094999865b08b1a811504", "bytes": 6832, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[2]/table-wrap[2]#ijms-22-08592-t002", "version": null, "note": "Protein regulation in the temporal quadrant 2 weeks after pONT compared to contralateral control (p < 0.05 and fold-change log2 > 0.43 (upregulation) or ≤ −0.43 (downregulation)). R = right; L = left; FC = fold change.", "structure": {"pmcid": "PMC8395271", "section_index": 2, "section_title": "2. Results", "row_count": 65, "column_count": 5}, "table": {"label": "Table 2", "caption": "Protein regulation in the temporal quadrant 2 weeks after pONT compared to contralateral control (p < 0.05 and fold-change log2 > 0.43 (upregulation) or ≤ −0.43 (downregulation)). R = right; L = left; FC = fold change.", "rows": [["Uniprot", "Protein Name", "FC L/R", "LogFC", "p-Value"], ["Upregulation"], ["M0R9G2 (P06238)", "Alpha-2-macroglobulin", "3.02", "1.59", "0.00"], ["P11883", "Aldehyde dehydrogenase, dimeric NADP-preferring (EC 1.2.1.5) (Aldehyde dehydrogenase family 3 member A1) (HTC-ALDH) (Tumor-associated aldehyde dehydrogenase)", "2.61", "1.39", "0.01"], ["G3V836", "Clusterin", "2.33", "1.22", "0.00"], ["P01048", "T-kininogen 1 (Alpha-1-MAP) (Major acute phase protein) (T-kininogen I) (Thiostatin) (cleaved into: T-kininogen 1 heavy chain (T-kininogen I heavy chain); T-kinin; T-kininogen 1 light chain (T-kininogen I light chain))", "2.33", "1.21", "0.04"], ["P52631", "Signal transducer and activator of transcription 3", "2.22", "1.15", "0.02"], ["A0A0G2QC06", "Serotransferrin", "2.16", "1.11", "0.02"], ["F1LM19", "Alpha-2-HS-glycoprotein", "2.03", "1.02", "0.03"], ["D3ZVR7", "Prostamide/prostaglandin F synthase (Prostamide/PG F synthase) (Prostamide/PGF synthase) (EC 1.11.1.20)", "2.03", "1.02", "0.04"], ["D3ZS58", "NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 2", "1.98", "0.99", "0.04"], ["P02767", "Transthyretin (Prealbumin) (TBPA)", "1.92", "0.94", "0.03"], ["G3V7F1", "G protein beta subunit-like, isoform CRA_a (Target of rapamycin complex subunit LST8)", "1.90", "0.92", "0.03"], ["G3V8Q4", "Retinol binding protein 3, interstitial (Retinol-binding protein 3)", "1.83", "0.87", "0.02"], ["P47819", "Glial fibrillary acidic protein (GFAP)", "1.79", "0.84", "0.01"], ["A0A0G2JUT0", "Heat shock-related 70 kDa protein 2", "1.65", "0.73", "0.03"], ["A0A0G2K151", "Apolipoprotein E", "1.63", "0.70", "0.04"], ["Q63041", "Alpha-1-macroglobulin (Alpha-1-M) (Alpha-1-macroglobulin 165 kDa subunit) (cleaved into: Alpha-1-macroglobulin 45 kDa subunit)", "1.62", "0.70", "0.04"], ["Q9QYU4", "Ketimine reductase mu-crystallin (EC 1.5.1.25) (CDK108) (NADP-regulated thyroid-hormone-binding protein)", "1.62", "0.70", "0.01"], ["Q07936", "Annexin A2 (Annexin II) (Annexin-2) (Calpactin I heavy chain) (Calpactin-1 heavy chain) (Chromobindin-8) (Lipocortin II) (Placental anticoagulant protein IV) (PAP-IV) (Protein I) (p36)", "1.61", "0.68", "0.00"], ["Q5XFX0", "Transgelin-2", "1.58", "0.66", "0.01"], ["G3V7K3", "Ceruloplasmin (Ceruloplasmin, isoform CRA_a)", "1.56", "0.64", "0.02"], ["Q4V8F6", "Pcbp2 protein (Poly(rC)-binding protein 2)", "1.51", "0.59", "0.03"], ["Q5RJR2", "Twinfilin-1", "1.50", "0.59", "0.03"], ["A0A0G2KB52", "Microtubule-associated protein 7", "1.50", "0.56", "0.04"], ["M0R9D5", "“Obsolete”", "1.47", "0.55", "0.03"], ["D3ZTB5", "S100 calcium-binding protein A13", "1.47", "0.55", "0.05"], ["G3V818", "Alpha-parvin (Parvin, alpha, isoform CRA_a)", "1.45", "0.54", "0.03"], ["Q5XI38", "Lymphocyte cytosolic protein 1", "1.44", "0.53", "0.01"], ["H1UBN0", "Copine-7 (Copine VII)", "1.43", "0.52", "0.01"], ["P62870", "Elongin-B (EloB) (Elongin 18 kDa subunit) (RNA polymerase II transcription factor SIII subunit B) (SIII p18) (Transcription elongation factor B polypeptide 2)", "1.39", "0.48", "0.01"], ["Q63798", "Proteasome activator complex subunit 2 (11S regulator complex subunit beta) (REG-beta) (Activator of multicatalytic protease subunit 2) (Proteasome activator 28 subunit beta) (PA28b) (PA28beta)", "1.38", "0.47", "0.01"], ["P97608", "5-oxoprolinase (EC 3.5.2.9) (5-oxo-L-prolinase) (5-OPase) (Pyroglutamase)", "1.38", "0.47", "0.03"], ["F1M9N7", "Arf-GAP domain and FG repeat-containing protein 1", "1.37", "0.46", "0.05"], ["D4A7F2", "Myc-binding protein (RCG31143)", "1.37", "0.45", "0.03"], ["P52759", "2-iminobutanoate/2-iminopropanoate deaminase (EC 3.5.99.10) (Liver perchloric acid-soluble protein) (L-PSP) (Reactive intermediate imine deaminase A homolog) (Translation inhibitor L-PSP ribonuclease) (EC 3.1.-.-) (UK114 antigen homolog) (rp14.5)", "1.37", "0.45", "0.03"], ["F2Z3T8", "Guanine nucleotide-binding protein subunit gamma", "1.36", "0.45", "0.04"], ["M0R567", "Interferon regulatory factor 2-binding protein-like", "1.35", "0.44", "0.00"], ["A1L1L5", "Ccnk protein (Cyclin K)", "1.35", "0.43", "0.00"], ["Downregulation"], ["D4ADS8 (Rab4a)", "Ras-related protein Rab-4A", "0.74", "−0.43", "0.01"], ["G3V6W2", "Prolactin regulatory element-binding protein (RCG62389, isoform CRA_a)", "0.74", "−0.44", "0.04"], ["D4ADS4", "Microsomal glutathione S-transferase 3 (RCG46430)", "0.72", "−0.45", "0.01"], ["P11275", "Calcium/calmodulin-dependent protein kinase type II subunit alpha (CaM kinase II subunit alpha) (CaMK-II subunit alpha) (EC 2.7.11.17)", "0.72", "−0.46", "0.02"], ["Q6XDA0", "Spectrin beta chain", "0.72", "−0.48", "0.00"], ["Q6IMZ3", "Annexin", "0.70", "−0.48", "0.01"], ["D3ZPC4", "Neural cell adhesion molecule L1", "0.70", "−0.51", "0.02"], ["Q32Q88", "F-box protein 22 (RCG58340, isoform CRA_b)", "0.70", "−0.52", "0.00"], ["Q4V7F2", "Cysteine-rich with EGF-like domain protein 1", "0.70", "−0.52", "0.04"], ["O09032", "ELAV-like protein 4 (Hu-antigen D) (HuD) (Paraneoplastic encephalomyelitis antigen HuD)", "0.69", "−0.53", "0.00"], ["P97846", "Contactin-associated protein 1 (Caspr) (Caspr1) (Neurexin IV) (Neurexin-4) (Paranodin) (p190)", "0.69", "−0.53", "0.02"], ["Q6PW52", "GABA-A gamma2 long isoform (Gamma-aminobutyric acid A receptor, gamma 2) (Gamma-aminobutyric acid receptor subunit gamma-2)", "0.68", "−0.55", "0.01"], ["O35760", "Isopentenyl-diphosphate Delta-isomerase 1 (EC 5.3.3.2) (Isopentenyl pyrophosphate isomerase 1) (IPP isomerase 1) (IPPI1)", "0.68", "−0.56", "0.01"], ["G3V679", "Transferrin receptor protein 1 (Transferrin receptor, isoform CRA_a)", "0.68", "−0.56", "0.02"], ["P12839", "Neurofilament medium polypeptide (NF-M) (160 kDa neurofilament protein) (Neurofilament 3) (Neurofilament triplet M protein)", "0.66", "−0.60", "0.04"], ["P62762", "Visinin-like protein 1 (VILIP) (21 kDa CABP) (Neural visinin-like protein 1) (NVL-1) (NVP-1)", "0.66", "−0.60", "0.00"], ["G3V7U2", "Microtubule-associated protein 1 A, isoform CRA_c (Microtubule-associated protein 1A)", "0.65", "−0.62", "0.00"], ["P63041", "Complexin-1 (Complexin I) (CPX I) (Synaphin-2)", "0.62", "−0.69", "0.00"], ["F1LRZ7", "Neurofilament heavy polypeptide", "0.61", "−0.71", "0.01"], ["P01830", "Thy-1 membrane glycoprotein (Thy-1 antigen) (CD antigen CD90)", "0.57", "−0.81", "0.00"], ["G3V774", "F-box only protein 2 (F-box protein 2)", "0.56", "−0.83", "0.02"], ["P19527", "Neurofilament light polypeptide (NF-L) (68 kDa neurofilament protein) (Neurofilament triplet L protein)", "0.54", "−0.88", "0.01"], ["A0A0G2JZL9", "Endothelial cell-selective adhesion molecule", "0.53", "−0.90", "0.03"], ["A0A0G2K0T6", "Gamma-synuclein", "0.38", "−1.41", "0.00"], ["F1LUD3", "AHNAK nucleoprotein 2", "0.30", "−1.74", "0.01"]], "row_count": 65, "column_count": 5, "numeric_cells": 265, "header_rows": 1, "locator": "section[2]/table-wrap[2]#ijms-22-08592-t002"}}, {"id": "asset:table:pmid:34445296:3", "role": "table", "format": 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R = right; L = left; FC = fold change.", "structure": {"pmcid": "PMC8395271", "section_index": 2, "section_title": "2. Results", "row_count": 28, "column_count": 5}, "table": {"label": "Table 3", "caption": "Protein regulation in the nasal quadrant 2 weeks after pONT compared to contralateral control (p < 0.05 and FC log2 > 0.43 (upregulation) or ≤ −0.43 (downregulation)). R = right; L = left; FC = fold change.", "rows": [["Uniprot", "Protein Name", "FC L/R", "LogFC", "p-Value"], ["Upregulation"], ["Q5U2P2", "Immunoglobulin superfamily member 11 (IgSF11)", "3.17", "1.67", "0.02"], ["D3ZZU8", "Fructosamine 3 kinase (Similar to fructosamine-3-kinase (Predicted), isoform CRA_a)", "2.47", "1.31", "0.02"], ["Q6MGB4", "H2-K region expressed gene 4, rat orthologue (RCG60794, isoform CRA_a) (Solute carrier family 39 (Zinc transporter), member 7) (Solute carrier family 39 member 7)", "2.07", "1.05", "0.00"], ["P47819", "Glial fibrillary acidic protein (GFAP)", "1.96", "0.97", "0.02"], ["Q5BJQ2", "Ubiquitin carboxyl-terminal hydrolase MINDY-1 (EC 3.4.19.12) (Deubiquitinating enzyme MINDY-1) (Protein FAM63A)", "1.86", "0.90", "0.01"], ["F1M118", "“Obsolete”", "1.85", "0.89", "0.02"], ["D3ZKK3", "Consortin, connexin sorting protein", "1.70", "0.77", "0.04"], ["D3ZPC4", "Neural cell adhesion molecule L1", "1.68", "0.75", "0.00"], ["Q6QI79", "Cap-specific mRNA (nucleoside-2′-O-)-methyltransferase 1 (LRRG00129)", "1.60", "0.68", "0.03"], ["F2Z3T8", "Guanine nucleotide-binding protein subunit gamma", "1.60", "0.68", "0.00"], ["F1M9D6", "Signal transducer and activator of transcription", "1.58", "0.66", "0.05"], ["P14056", "Serine/threonine-protein kinase A-Raf (EC 2.7.11.1) (Proto-oncogene A-Raf) (Proto-oncogene A-Raf-1)", "1.55", "0.63", "0.04"], ["O88775", "Embigin", "1.54", "0.62", "0.02"], ["Q6AYE2", "Endophilin-B1 (SH3 domain-containing GRB2-like protein B1)", "1.52", "0.61", "0.03"], ["G3V836", "Clusterin", "1.52", "0.60", "0.03"], ["P14480", "Fibrinogen beta chain (Liver regeneration-related protein LRRG036/LRRG043/LRRG189) (cleaved into: Fibrinopeptide B; Fibrinogen beta chain)", "1.51", "0.60", "0.01"], ["Q9EPF2", "Cell surface glycoprotein MUC18 (Gicerin) (Melanoma cell adhesion molecule) (Melanoma-associated antigen MUC18) (CD antigen CD146)", "1.47", "0.56", "0.02"], ["A0A0G2JUB0", "Protein FAM3C", "1.40", "0.49", "0.04"], ["P62193", "26S proteasome regulatory subunit 4 (P26s4) (26S proteasome AAA-ATPase subunit RPT2) (Proteasome 26S subunit ATPase 1)", "1.39", "0.48", "0.01"], ["M0R567", "Interferon regulatory factor 2-binding protein-like", "1.38", "0.46", "0.00"], ["Downregulation"], ["P63041", "Complexin-1 (Complexin I) (CPX I) (Synaphin-2)", "0.66", "−0.59", "0.02"], ["G3V7W1", "Programmed cell death protein 6 (Apoptosis-linked gene 2 protein homolog) (ALG-2)", "0.60", "−0.73", "0.01"], ["Q62813", "Limbic system-associated membrane protein", "0.56", "−0.82", "0.00"], ["D3ZDX5", "Plexin B1", "0.55", "−0.87", "0.04"], ["D4ABV0", "RGD1566320 (RGD1566320 (predicted))", "0.43", "−1.20", "0.01"]], "row_count": 28, "column_count": 5, "numeric_cells": 99, "header_rows": 1, "locator": "section[2]/table-wrap[3]#ijms-22-08592-t003"}}, {"id": "asset:table:pmid:34445296:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5018a6d18643148d1f7bfdde1a43481c6a1999a6953e302d014584aae871e030", "bytes": 667, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[2]/table-wrap[4]#ijms-22-08592-t004", "version": null, "note": "Bioinformatic analysis using SWATH-based proteomic data obtained from temporal (T) and nasal (N) retinal quadrants at 2 weeks after pONT compared to the corresponding contralateral control (T/N). R = right eye; L = left eye.", "structure": {"pmcid": "PMC8395271", "section_index": 2, "section_title": "2. Results", "row_count": 3, "column_count": 8}, "table": {"label": "Table 4", "caption": "Bioinformatic analysis using SWATH-based proteomic data obtained from temporal (T) and nasal (N) retinal quadrants at 2 weeks after pONT compared to the corresponding contralateral control (T/N). R = right eye; L = left eye.", "rows": [["", "Differentially Expressed Genes", "Genes with Measured Expression", "Gene Ontology TERMS", "miRNAs", "Upstream Regulators", "Chemical Upstream Regulators", "Associated Diseases"], ["LT vs. RT", "59", "2910", "842", "6", "72", "103", "27"], ["LN vs. RN", "24", "2901", "339", "0", "30", "72", "12"]], "row_count": 3, "column_count": 8, "numeric_cells": 14, "header_rows": 1, "locator": "section[2]/table-wrap[4]#ijms-22-08592-t004"}}, {"id": "asset:table:pmid:34445296:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e2a819f34570f59811a74518de36a16a283d86cd1a3ec8531359da548647601a", "bytes": 846, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[2]/table-wrap[5]#ijms-22-08592-t005", "version": null, "note": "Pathway analysis of regulated proteins in temporal and nasal quadrants 2 weeks after pONT.", "structure": {"pmcid": "PMC8395271", "section_index": 2, "section_title": "2. Results", "row_count": 13, "column_count": 4}, "table": {"label": "Table 5", "caption": "Pathway analysis of regulated proteins in temporal and nasal quadrants 2 weeks after pONT.", "rows": [["Pathway Name", "Pathway ID", "p-Value", "p-Value (FDR)"], ["LT vs. RT"], ["Ferroptosis", "04216", "5.332 × 10−4", "0.063"], ["HIF-1 signaling pathway", "04066", "0.002", "0.133"], ["Adipocytokine signaling pathway", "04920", "0.013", "0.527"], ["Necroptosis", "04217", "0.022", "0.594"], ["Cell adhesion molecules", "04514", "0.026", "0.584"], ["LN vs. RN"], ["Complement and coagulation cascades", "04610", "0.005", "0.401"], ["Hepatitis B", "05161", "0.018", "0.408"], ["Jak-STAT signaling pathway", "04630", "0.019", "0.408"], ["Pancreatic cancer", "05212", "0.024", "0.408"], ["Serotonergic synapse", "04726", "0.030", "0.408"]], "row_count": 13, "column_count": 4, "numeric_cells": 31, "header_rows": 1, "locator": "section[2]/table-wrap[5]#ijms-22-08592-t005"}}, {"id": "asset:table:pmid:34445296:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:01b33ac486da39fe72b337d676ba0be5f771f8b1da88136a14d508150266a6a6", "bytes": 2194, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[2]/table-wrap[6]#ijms-22-08592-t006", "version": null, "note": "Gene ontology analysis of temporal and nasal quadrants 2 weeks after pONT.", "structure": {"pmcid": "PMC8395271", "section_index": 2, "section_title": "2. Results", "row_count": 17, "column_count": 7}, "table": {"label": "Table 6", "caption": "Gene ontology analysis of temporal and nasal quadrants 2 weeks after pONT.", "rows": [["Results", "LT vs. RT", "LN vs. RN"], ["GO Term", "p-Value", "p-Value (FDR)", "GO Term", "p-Value", "p-Value (FDR)"], ["Molecular functions", "Signaling receptor binding", "2.600 × 10−4", "0.054", "mRNA (nucleoside-2′-O-)-methyltransferase activity", "0.008", "0.222"], ["Protein-containing complex binding", "2.800 × 10−4", "0.054", "Fructosamine-3-kinase activity", "0.008", "0.222"], ["Thyroid hormone binding", "0.001", "0.130", "Cell adhesion molecule binding", "0.012", "0.222"], ["Structural constituent of postsynaptic intermediate filament cytoskeleton", "0.001", "0.130", "Signaling receptor binding", "0.013", "0.222"], ["Tau protein binding", "0.002", "0.130", "PDZ domain binding", "0.014", "0.222"], ["Biological processes", "Intermediate filament organization", "2.000 × 10−7", "5.018 × 10−4", "Homophilic cell adhesion via plasma membrane adhesion molecules", "2.700 × 10−4", "0.207"], ["Supramolecular fiber organization", "6.300 × 10−7", "5.854 × 10−4", "Positive regulation of multicellular organismal process", "6.900 × 10−4", "0.207"], ["Neuron projection regeneration", "7.000 × 10−7", "5.854 × 10−4", "Cell adhesion", "0.001", "0.207"], ["Intermediate filament-based process", "6.600 × 10−6", "0.002", "Biological adhesion", "0.001", "0.207"], ["Intermediate filament cytoskeleton organization", "6.600 × 10−6", "0.002", "Cell-cell adhesion via plasma-membrane adhesion molecules", "0.001", "0.207"], ["Cellular components", "Postsynaptic intermediate filament cytoskeleton", "3.400 × 10−5", "0.013", "Side of Membrane", "0.002", "0.310"], ["Neurofibrillary tangle", "8.400 × 10−5", "0.015", "External side of plasma membrane", "0.007", "0.310"], ["Axon", "1.700 × 10−4", "0.018", "Spherical high-density lipoprotein particle", "0.008", "0.310"], ["Schaffer collateral—CA1 synapse", "3.900 × 10−4", "0.018", "Cytoplasmic side of lysosomal membrane", "0.008", "0.310"], ["Neuronal cell body", "4.100 × 10−4", "0.018", "Perinuclear endoplasmic reticulum lumen", "0.008", "0.310"]], "row_count": 17, "column_count": 7, "numeric_cells": 62, "header_rows": 2, "locator": "section[2]/table-wrap[6]#ijms-22-08592-t006"}}], "gaps": ["asset:data:geo:PXD026783 not downloaded", "asset:data:geo:PXD026783 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "regression_modelling", "specific": "ols", "label": "Regression modelling", "dsl_operations": ["ols_fit"], "missing_operations": [], "expressible": true, "parameters": {"r_squared": "S and MRM-MS (temporal, R2 = 0"}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.7, "band": "medium", "quote": "Linear regression"}}, {"id": "method-2", "family": null, "specific": null, "label": "paired t-test", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Samples were normalized by most likely ratio (MLR) normalization with a paired t-test used to detect significantly differentiated proteins in biological samples among experimental groups."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["ols_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ols."}, "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": ["PXD026783"], "resolved_accessions": ["PXD026783"], "statements": ["The data presented in this study are available in this article and Supplementary Materials section."], "basis": "The paper names PXD026783 in ProteomeXchange and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["ols_fit"], "assets": ["source:pmid:34445296", "data:geo:PXD026783", "asset:table:pmid:34445296:1", "asset:table:pmid:34445296:2", "asset:table:pmid:34445296:3", "asset:table:pmid:34445296:4", "asset:table:pmid:34445296:5", "asset:table:pmid:34445296:6"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD026783"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 49438, "completion_tokens": 1112, "cached_tokens": 16648}}, "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:34445296", "type": "paper", "label": "pmid:34445296"}, {"id": "source:pmid:34445296", "type": "manuscript", "label": "PMID 34445296 full text"}, {"id": "data:geo:PXD026783", "type": "dataset", "label": "GEO PXD026783"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34445296", "type": "paper", "label": "pmid:34445296"}, {"id": "source:pmid:34445296", "type": "manuscript", "label": "PMID 34445296 full text"}, {"id": "data:geo:PXD026783", "type": "dataset", "label": "GEO PXD026783"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34445296", "type": "extraction", "used": ["source:pmid:34445296"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD026783", "type": "accession_resolution", "used": ["data:geo:PXD026783"], "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:34445296", "parent_hash": "sha256:ab12a83a33f316f7214d6c7f6aa83322f7427b9b400e92448b3c7cf440d6d8df", "fork_of": null, "generation": 5}, "gaps": ["asset:data:geo:PXD026783 licence not read", "asset:data:geo:PXD026783 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ntified by Integrated SWATH and Target-Based Proteomics.", "pathways, SWATH label-free and target-based mass spectrometry was employed to identify the proteomes in va", "resolution hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS), and SWATH-based acquisition, and", "er validated by multiple reaction monitoring mass spectrometry (MRM-MS). A total of 3641 proteins (FDR < 1%"], "order_basis": "paper_text_order:103", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["section (pONT) was performed on adult Wistar rats and their retinas were harvested 2 weeks lat", "UCLA Animal Research Committee. Adult Wistar rats (3 months-old; 300–350 g) were housed with s", "e Homogenization and Protein Extraction Four rat retina tissues (rat number 203,204, 205, and", "Protein Extraction Four rat retina tissues (rat number 203,204, 205, and 206) were used for"], "order_basis": "paper_text_order:513", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["n of primary and secondary RGC degeneration, immunohistochemistry of RNA binding protein with multiple splicin"], "order_basis": "paper_text_order:635", "id": "assay:3"}, {"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["ols_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["Linear regression"], "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":"2026-11-04T03:12:33+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}}}