Comprehensive analysis of angiogenesis-related genes and pathways in early diabetic retinopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32993645", "kind": "science-record", "revision": 7, "content_hash": "sha256:01fa052783bd0f894a7e84a9082d673ec626b0ca0c00db37ac20b28276a783cf", "created_at": "2026-11-01T15:41:11Z", "updated_at": "2026-11-01T22:02:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of angiogenesis-related genes and pathways in early diabetic retinopathy.", "doi": "10.1186/s12920-020-00799-6", "pmid": "32993645", "authors": ["Chufeng Gu", "Thashi Lhamo", "Chen Zou", "Chuandi Zhou", "Tong Su", "Deji Draga", "Dawei Luo", "Zhi Zheng", "Lili Yin", "Qinghua Qiu"], "journal": "BMC medical genomics", "year": 2020, "abstract": "BACKGROUND: Angiogenesis is an important parameter in the development of diabetic retinopathy (DR), and it is indicative of an early stage evolving into a late phase. Therefore, examining the role of angiogenic factors in early DR is crucial to understanding the mechanism of neovascularization.\nMETHODS: The present study identified hub genes and pathways associated with angiogenesis in early DR using bioinformatics analysis. Genes from published literature and Gene Expression Omnibus (GEO) were collected and analysed.\nRESULTS: We collected 73 genes from 70 published studies in PubMed, which were referred to as DR-related gene set 1 (DRgset1). The gene expression profile of GSE12610 was downloaded, and 578 differentially expressed genes (DEGs) between diabetic and normal samples were identified. DEGs and DRgset1 were further combined to create DR-related gene set 2 (DRgset2). After an enrichment analysis, we identified 12 GO terms and 2 pathways associated with neovascularization in DRgset1, and 8 GO terms and 2 pathways in DRgset2. We found 39 new genes associated with angiogenesis and verified 8 candidate angiogenesis-related genes in DR cells using real-time PCR: PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1. We identified 10 hub genes associated with neovascularization by constructing a protein-protein interaction (PPI) network: TNF, VEGFA, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1.\nCONCLUSIONS: The present study analysed angiogenesis-related genes and pathways in early DR in a comprehensive and systematic manner. PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1 may be the candidate genes to further explore the mechanisms of angiogenesis in early DR. TNF, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1 may be new targets for early neovascularization therapy in the future.", "claims": [{"id": "claim-data-access", "statement": "All data generated or analysed during this study are included in this published article and its supplementary information files. The raw matrix datasets can be downloaded from the Gene Expression Omnibus (GEO) database by searching “GSE12610” (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12610).\nGPL1261 annotation files can be required from the website: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL1261.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32993645", "locator": "sections[28] \"Availability of data and materials\" paragraphs 1-3", "quote": "All data generated or analysed during this study are included in this published article and its supplementary information files. The raw matrix datasets can be downloaded from the Gene Expression Omnibus (GEO) database by searching “GSE12610” (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12610).\nGPL1261 annotation files can be required from the website: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL1261."}], "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:32993645"], "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:GSE12610"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE12610"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32993645", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12920-020-00799-6", "sha256": "sha256:010ee6ae8393fd99cd083cd0522786498ece83a21d500ed496f490172d5e3674", "bytes": 39223, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12920-020-00799-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7526206", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12610", "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=GSE12610", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12610", "version": null, "note": "All data generated or analysed during this study are included in this published article and its supplementary information files. The raw matrix datasets can be downloaded from the Gene Expression Omnibus (GEO) database by searching “GSE12610” (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12610).\nGPL1261 annotation files can be required from the website: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL1261.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analysed during this study are included in this published article and its supplementary information files. The raw matrix datasets can be downloaded from the Gene Expression Omnibus (GEO) database by searching “GSE12610” (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12610).\nGPL1261 annotation files can be required from the website: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL1261.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM315892", "GSM315893", "GSM315894", "GSM315895", "GSM315896"], "sample_count": 5, "group_sizes": null, "group_sizes_basis": null, "platform": "1261", "taxon": "Mus musculus", "title": "Diabetes and the retina (eldre-affy-mouse-319092)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:32993645:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:60551f5f6c9772bd4211b501c6e01b51e7ce67bac7fc35aaa4980962df7b887c", "bytes": 1826, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#Tab1", "version": null, "note": "GO-BP terms related to neovascularization shared by GO1 and GO2", "structure": {"pmcid": "PMC7526206", "section_index": 17, "section_title": "Enrichment analysis of DRgset2", "row_count": 8, "column_count": 3}, "table": {"label": "Table 1", "caption": "GO-BP terms related to neovascularization shared by GO1 and GO2", "rows": [["GO-BP terms", "Genes in GO1", "Genes in GO2"], ["positive regulation of smooth muscle cell proliferation", "NAMPT, TNF, PDGFB, PTGS2, EDN1, PPARGC1A", "PRKCA, NAMPT, TNF, PDGFB, PTGS2, AIF1, EDN1, AGER, PPARGC1A, HIF1A, VEGFA, THBS1, ALOX12"], ["positive regulation of MAP kinase activity", "EDN3, TNF, PDGFB, PDGFA, EDN1, VEGFA, TGFB1", "EDN3, TNF, PDGFB, PDGFA, VEGFA, EDN1, TPD52L1, FGF1, TGFB1"], ["positive regulation of cell proliferation", "VIP, NAMPT, EDN3, NTF3, PDGFB, PGF, PDGFA, EDN1, HGF, GDNF, TGFB1, CXCL10, CNTF, VEGFA", "EDN3, TNF, PTGS2, PDGFB, PGF, PDGFA, EDN2, EDN1, FGF10, GDNF, GHRHR, TGFB1, CXCL10, ALDH3A1, EDNRA, GADD45GIP1, THBS1, FGF1, TRAF5, APLN, NTF3, HGF, PLAC8, OSM, PRAMEF12, CNTF, HIF1A, VEGFA, ALOX12, NGF"], ["positive regulation of cell migration", "PRKCA, NTF3, PDGFB, PDGFA, SEMA3E, EDN1, VEGFA, HGF, TGFB1", "PRKCA, PDGFB, NTF3, PDGFA, AIF1, EDN1, HGF, AQP1, MMP2, AGER, TGFB1, CXCL10, VEGFA, SEMA3E, SEMA3C, COL1A1, THBS1, FGF1, MYOC, ALOX12"], ["positive regulation of blood vessel endothelial cell migration", "PRKCA, PDGFB, VEGFA, HSPB1, ANGPT1, TGFB1", "PRKCA, PDGFB, VEGFA, HSPB1, ANGPT1, THBS1, TGFB1"], ["positive regulation of angiogenesis", "PRKCA, UTS2, PGF, CXCL8, HGF, AQP1, PTGIS, HIF1A, VEGFA, HSPB1, ANGPT2, ANGPTL4", "PRKCA, UTS2, PGF, MMP9, C6, HGF, AQP1, TNFRSF1A, HIF1A, PTGIS, VEGFA, HSPB1, UTS2R, FGF1, THBS1, ANGPT2, ALOX12"], ["angiogenesis", "PRKCA, HIF1A, CCL2, PTGS2, PDGFA, PGF, VEGFA, CXCL8, ANGPT1, ANGPT2, ANGPTL4", "PRKCA, COL4A1, CCL2, PTGS2, PDGFA, PGF, FGF10, MMP2, HOXB3, TAL1, HIF1A, DLL4, FAP, VEGFA, SEMA3E, ANGPT1, COL8A1, FGF1, COL8A2, ANGPT2, ANGPTL4"]], "row_count": 8, "column_count": 3, "numeric_cells": 7, "header_rows": 1, "locator": "section[17]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:32993645:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6e3ab26e4073bdda5d44c5c3834a600870f378f889eaa6be563347c7397d23f0", "bytes": 742, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[2]#Tab2", "version": null, "note": "KEGG pathways related to neovascularization shared by KEGG1 and KEGG2", "structure": {"pmcid": "PMC7526206", "section_index": 17, "section_title": "Enrichment analysis of DRgset2", "row_count": 3, "column_count": 3}, "table": {"label": "Table 2", "caption": "KEGG pathways related to neovascularization shared by KEGG1 and KEGG2", "rows": [["KEGG pathway", "Genes in KEGG1", "Genes in KEGG2"], ["TNF signaling pathway", "VCAM1, ICAM1, TNFRSF1A, TNFRSF1B, TNF, CCL2, PTGS2, MMP9, EDN1, CXCL10", "ICAM1, TNF, CCL2, PTGS2, PIK3CB, MMP9, EDN1, IFI47, CXCL10, VCAM1, TNFRSF1A, TNFRSF1B, MAPK13, TRAF5"], ["PI3K-Akt signaling pathway", "PRKCA, IL2RA, PDGFB, PDGFA, PGF, VEGFA, TLR4, ANGPT1, HGF, ANGPT2, NGF", "PRKCA, COL4A1, IL2RA, PDGFB, PDGFA, PGF, PIK3CB, TCL1B4, FGF23, FGF10, TLR4, HGF, OSM, CCNE2, VEGFA, ITGA7, ANGPT1, COL1A1, THBS1, FGF1, COL24A1, ANGPT2, THBS4, NGF"]], "row_count": 3, "column_count": 3, "numeric_cells": 3, "header_rows": 1, "locator": "section[17]/table-wrap[2]#Tab2"}}], "gaps": ["asset:data:geo:GSE12610 not downloaded", "asset:data:geo:GSE12610 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE12610"], "resolved_accessions": ["GSE12610"], "statements": ["All data generated or analysed during this study are included in this published article and its supplementary information files. The raw matrix datasets can be downloaded from the Gene Expression Omnibus (GEO) database by searching “GSE12610” (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12610).\nGPL1261 annotation files can be required from the website: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL1261."], "basis": "The paper names GSE12610 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:32993645", "data:geo:GSE12610", "asset:table:pmid:32993645:1", "asset:table:pmid:32993645:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE12610"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:11:51Z", "independence": "single_reader"}, "evidence_check": {"method": "absent", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 33622, "completion_tokens": 1615, "cached_tokens": 792}}, "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:32993645", "type": "paper", "label": "pmid:32993645"}, {"id": "source:pmid:32993645", "type": "manuscript", "label": "PMID 32993645 full text"}, {"id": "data:geo:GSE12610", "type": "dataset", "label": "GEO GSE12610"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32993645", "type": "paper", "label": "pmid:32993645"}, {"id": "source:pmid:32993645", "type": "manuscript", "label": "PMID 32993645 full text"}, {"id": "data:geo:GSE12610", "type": "dataset", "label": "GEO GSE12610"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32993645", "type": "extraction", "used": ["source:pmid:32993645"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE12610", "type": "accession_resolution", "used": ["data:geo:GSE12610"], "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:32993645", "parent_hash": "sha256:0da307321b8aaa8b4524176483179969b626e25a9da5fb89dfaf58d474c32295", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE12610 licence not read", "asset:data:geo:GSE12610 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["angiogenesis-related genes in DR cells using real-time PCR: PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A"], "order_basis": "paper_text_order:1221", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["y Research Institute (Kirkland, WA, USA) and cultured in M199 medium supplemented with 20% foetal bov"], "order_basis": "paper_text_order:2074", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["primarily related to hypoxia, inflammation, apoptosis, and angiogenesis. We found 12 terms associa", "primarily related to hypoxia, inflammation, apoptosis, and angiogenesis. We found 8 terms associat"], "order_basis": "paper_text_order:2816", "id": "assay:3"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}