Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis Using Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29226137", "kind": "science-record", "revision": 8, "content_hash": "sha256:83aeb300716f6500f2847e2dcb849fc602d529683e6649ff1e9187bab275d194", "created_at": "2026-11-01T15:40:30Z", "updated_at": "2026-11-01T21:59:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis Using Bioinformatics Analysis.", "doi": "10.1155/2017/4323496", "pmid": "29226137", "authors": ["Xiaowen Tan", "Xiting Zhang", "Lanlan Pan", "Xiaoxuan Tian", "Pengzhi Dong"], "journal": "BioMed research international", "year": 2017, "abstract": "BACKGROUND: Coronary artery atherosclerosis is a chronic inflammatory disease. This study aimed to identify the key changes of gene expression between early and advanced carotid atherosclerotic plaque in human.\nMETHODS: Gene expression dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO), including 16 advanced and 13 early stage atherosclerotic plaque samples from human carotid. Differentially expressed genes (DEGs) were analyzed.\nRESULTS: 42,450 genes were obtained from the dataset. Top 100 up- and downregulated DEGs were listed. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) identification were performed. The result of functional and pathway enrichment analysis indicted that the immune system process played a critical role in the progression of carotid atherosclerotic plaque. Protein-protein interaction (PPI) networks were performed either. Top 10 hub genes were identified from PPI network and top 6 modules were inferred. These genes were mainly involved in chemokine signaling pathway, cell cycle, B cell receptor signaling pathway, focal adhesion, and regulation of actin cytoskeleton.\nCONCLUSION: The present study indicated that analysis of DEGs would make a deeper understanding of the molecular mechanisms of atherosclerosis development and they might be used as molecular targets and diagnostic biomarkers for the treatment of atherosclerosis.", "claims": [{"id": "claim-method", "statement": "DEGs were identified using signal to noise method where a total of 42,450 genes were analyzed and top 100 (top 100 upregulated and top 100 downregulated genes) genes were listed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29226137", "locator": "sections[4] \"2.2. Identification of Differentially Expression Genes (DEGs)\" paragraph 2", "quote": "DEGs were identified using signal to noise method where a total of 42,450 genes were analyzed and top 100 (top 100 upregulated and top 100 downregulated genes) genes were listed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profiles of GSE28829 were downloaded from Gene Expression Omnibus (GEO). GSE28829 was performed on GPL570, [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. The GSE28829 data set contained 29 samples, including 16 advanced atherosclerotic plaque samples and 13 early atherosclerotic plaque samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29226137", "locator": "sections[3] \"2.1. Microarray Data\" paragraph 2", "quote": "The gene expression profiles of GSE28829 were downloaded from Gene Expression Omnibus (GEO). GSE28829 was performed on GPL570, [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. The GSE28829 data set contained 29 samples, including 16 advanced atherosclerotic plaque samples and 13 early atherosclerotic plaque samples."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using the signal-to-noise method on GSE28829 gene-expression data downloaded from GEO, the study identified C2 as the most significantly upregulated gene (score 1.792) and H2AFV as the most significantly downregulated gene (score −2.249).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29226137", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Gene expression dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO), including 16 advanced and 13 early stage atherosclerotic plaque samples from human carotid."}, {"asset": "source:pmid:29226137", "locator": "sections[4] \"2.2. Identification of Differentially Expression Genes (DEGs)\" paragraph 2", "quote": "DEGs were identified using signal to noise method where a total of 42,450 genes were analyzed and top 100 (top 100 upregulated and top 100 downregulated genes) genes were listed."}, {"asset": "source:pmid:29226137", "locator": "sections[9] \"3.1. Identification of Differentially Expressed Genes (DEGs)\" paragraph 2", "quote": "Among the total 42,450 genes, the most significant signal of upregulated gene is C2, and the signal to noise score is 1.792. The most significant signal of downregulated gene is H2AFV where the signal to noise score is −2.249."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using the signal-to-noise method on GSE28829 gene-expression data downloaded from GEO, the study identified C2 as the most significantly upregulated gene (score 1.792) and H2AFV as the most significantly downregulated gene (score −2.249).", "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:29226137"], "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:GSE28829"], "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:GSE28829"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29226137", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2017/4323496", "sha256": "sha256:d72f0f5f86e9dca3fe7ed9feb8316c19c4a64e36af134bd54a28d835762b0523", "bytes": 37036, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2017/4323496", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5684517", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE28829", "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=GSE28829", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE28829", "version": null, "note": "The gene expression profiles of GSE28829 were downloaded from Gene Expression Omnibus (GEO). GSE28829 was performed on GPL570, [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. The GSE28829 data set contained 29 samples, including 16 advanced atherosclerotic plaque samples and 13 early atherosclerotic plaque samples.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The gene expression profiles of GSE28829 were downloaded from Gene Expression Omnibus (GEO). GSE28829 was performed on GPL570, [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. The GSE28829 data set contained 29 samples, including 16 advanced atherosclerotic plaque samples and 13 early atherosclerotic plaque samples.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM714070", "GSM714071", "GSM714072", "GSM714073", "GSM714074", "GSM714075", "GSM714076", "GSM714077", "GSM714078", "GSM714079", "GSM714080", "GSM714081", "GSM714082", "GSM714083", "GSM714084", "GSM714085", "GSM714086", "GSM714087", "GSM714088", "GSM714089", "GSM714090", "GSM714091", "GSM714092", "GSM714093", "GSM714094", "GSM714095", "GSM714096", "GSM714097", "GSM714098"], "sample_count": 29, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene Expression in early and advanced atherosclerotic plaque from human carotid", "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:29226137:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1fed78a873ac5f751d59a34f4b91016a9de6652c58db37e905484c69e44e6b60", "bytes": 882, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#tab1", "version": null, "note": "Cellular component (GO) enrichment analysis in networks.", "structure": {"pmcid": "PMC5684517", "section_index": 10, "section_title": "3.2. Gene Ontology and Pathway Enrichment Analysis", "row_count": 12, "column_count": 5}, "table": {"label": "Table 1", "caption": "Cellular component (GO) enrichment analysis in networks.", "rows": [["Expression", "#Pathway ID", "Pathway description", "Observed gene count", "False discovery rate"], ["Upregulated", "GO.0005764", "Lysosome", "103", "1.02E − 25"], ["GO.0005773", "Vacuole", "112", "1.32E − 25"], ["GO.0005886", "Plasma membrane", "441", "1.46E − 25"], ["GO.0071944", "Cell periphery", "446", "1.46E − 25"], ["GO.0044459", "Plasma membrane part", "268", "1.30E − 24"], [""], ["Downregulated", "GO.0005737", "Cytoplasm", "807", "9.90E − 37"], ["GO.0043229", "Intracellular organelle", "838", "1.42E − 26"], ["GO.0044422", "Organelle part", "639", "3.03E − 26"], ["GO.0044444", "Cytoplasmic part", "611", "3.03E − 26"], ["GO.0044446", "Intracellular organelle part", "628", "3.03E − 26"]], "row_count": 12, "column_count": 5, "numeric_cells": 30, "header_rows": 1, "locator": "section[10]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:29226137:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:eff5eccfec84feefcd780d0162a433c468b90fd6dabe8ef1e696beeda02c7d38", "bytes": 894, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[2]#tab2", "version": null, "note": "Molecular function (GO) enrichment analysis in networks.", "structure": {"pmcid": "PMC5684517", "section_index": 10, "section_title": "3.2. Gene Ontology and Pathway Enrichment Analysis", "row_count": 12, "column_count": 5}, "table": {"label": "Table 2", "caption": "Molecular function (GO) enrichment analysis in networks.", "rows": [["Expression", "#Pathway ID", "Pathway description", "Observed gene count", "False discovery rate"], ["Upregulated", "GO.0005515", "Protein binding", "445", "7.57E − 24"], ["GO.0005102", "Receptor binding", "148", "1.76E − 16"], ["GO.0060089", "Molecular transducer activity", "194", "1.39E − 14"], ["GO.0003674", "Molecular_function", "889", "4.21E − 12"], ["GO.0005488", "Binding", "761", "4.21E − 12"], [""], ["Downregulated", "GO.0005515", "Protein binding", "426", "8.46E − 22"], ["GO.0005488", "Binding", "740", "3.00E − 12"], ["GO.0008092", "Cytoskeletal protein binding", "79", "7.43E − 12"], ["GO.0019899", "Enzyme binding", "151", "7.43E − 12"], ["GO.0000166", "Nucleotide binding", "218", "1.07E − 08"]], "row_count": 12, "column_count": 5, "numeric_cells": 30, "header_rows": 1, "locator": "section[10]/table-wrap[2]#tab2"}}, {"id": "asset:table:pmid:29226137:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:21244b63d9cfb9db6c876e804b50ddebab22277c0a52a850112e09d4e7fcb9e9", "bytes": 1029, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[3]#tab3", "version": null, "note": "Biological process (GO) enrichment analysis in networks.", "structure": {"pmcid": "PMC5684517", "section_index": 10, "section_title": "3.2. Gene Ontology and Pathway Enrichment Analysis", "row_count": 12, "column_count": 5}, "table": {"label": "Table 3", "caption": "Biological process (GO) enrichment analysis in networks.", "rows": [["Expression", "#Pathway ID", "Pathway description", "Observed gene count", "False discovery rate"], ["Upregulated", "GO.0002376", "Immune system process", "321", "7.44E − 63"], ["GO.0006952", "Defense response", "252", "5.46E − 56"], ["GO.0002682", "Regulation of immune system process", "246", "8.58E − 56"], ["GO.0006955", "Immune response", "241", "2.11E − 55"], ["GO.0050776", "Regulation of immune response", "175", "4.95E − 49"], [""], ["Downregulated", "GO.0007010", "Cytoskeleton organization", "109", "2.81E − 12"], ["GO.0016043", "Cellular component organization", "386", "2.81E − 12"], ["GO.0048522", "Positive regulation of cellular process", "362", "2.81E − 12"], ["GO.0051128", "Regulation of cellular component organization", "211", "6.71E − 12"], ["GO.0071840", "Cellular component organization or biogenesis", "390", "1.02E − 11"]], "row_count": 12, "column_count": 5, "numeric_cells": 30, "header_rows": 1, "locator": "section[10]/table-wrap[3]#tab3"}}, {"id": "asset:table:pmid:29226137:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a621ea75f8b3d7f05d3b3c8761c300a2e3400f872fdbdd349f1486ea004493b5", "bytes": 2112, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#tab5", "version": null, "note": "Top 6 modules from protein-protein interaction network.", "structure": {"pmcid": "PMC5684517", "section_index": 11, "section_title": "3.3. Module Screening from the Protein-Protein Interaction (PPI) Network", "row_count": 12, "column_count": 3}, "table": {"label": "Table 5", "caption": "Top 6 modules from protein-protein interaction network.", "rows": [["Gene set", "MCODE score", "Nodes"], ["Chemokine signaling pathway", "31.419", "CCL20, PNOC, PENK, LPAR5, C5AR1, CCR1, RGS1, ADRA2A, CXCL3, CXCL2, CCL21, CCR7, CCL19, FPR3, CCR5, CCL5, CXCL16, ADCY3, P2RY13, ADORA3, CCL16, IL8, RGS10, RGS19, CXCL1, C3, CCR2, C3AR1, CXCL12, GPR18, CXCR4, ADCY4"], [""], ["Cell cycle", "10.303", "KIF20A, PTTG1, HLA-B, CDK1, CASC5, IRF8, IRF4, CIITA, CKS2, IRF5, IRF1, IRF7, CCL4, UBE2C, KIF4A, CCNA2, AURKA, ZWINT, TOP2A, HLA-A, PTAFR, TYMS, CENPK, CCNB1, MLF1IP, HLA-C, NUSAP1, KNTC1, SGOL2, MCM4, PML, RCC2, CCNB2, TTK"], [""], ["B cell receptor signaling pathway", "9.762", "VWF, NCF4, SH3KBP1, PLEK, CD14, TNFSF13B, CD79A, BLNK, CD72, SPI1, PTPRC, KLRG1, IL2RB, PIK3CD, SYK, VAV3, CASP1, CDH5, PLCG2, FCER1G, SDC1, NCF1, INPP5D, PIK3R5, RAC2, CD22, NCF2, LYN, ACE, CYBA, DAPP1, ITGAL, HCLS1, MYD88, PRKCH, PAG1, ANPEP, CD36, THY1, SHC2, NOD2, HCK, CD2"], [""], ["Focal adhesion", "8.852", "TNS1, DLG1, NDE1, PPM1B, WDR1, RRAS, ITGB3, CNN1, SRSF1, CCND2, HNRNPD, IGF1R, TPM1, TPM2, EGFR, RHEB, TLN2, HNRNPU, PDS5B, SKA2, NUDC, PAFAH1B1, RHOQ, ABL1, CAP2, ACTG2, PPP3CB, TUBA4A, CORO1C, PAPOLA, RAF1, LAMA5, SF3B2, LAMC1, MAPRE1, ILKAP, RHOA, NDEL1, SRRM1, SRSF3, PPM1A, PPP2R5A, PPP1R12A, PPP1CB, ACTR3B, HNRNPA3, CYCS, ENAH, CLIP1, CLASP2, PPP2CB, RANBP2, PPP2R5C, VCL, ACTR3"], [""], ["Focal adhesion", "7.414", "YWHAZ, ITGA11, GNB5, KALRN, ROCK1, DNAJB4, SMAD4, S1PR3, DNAJC10, ITGB1, DNAJB6, ITGA8, ERBB2, FGF13, PDE4D, GNAS, PRKAR1A, CYFIP2, FRK, DNAJB5, CCND1, CASK, CRK, ADCY9, DLG3, HSPA4, HSPA4L, ADCY5, H2AFV, PDE3A, YAP1, PGR, MPP7, ITGA9, ROCK2, PDE8B, PCM1, PARVA, ADCY2, RAP1A, KAT7, ITGA7, DNAJA4, MAPK9, ACTN2, ZAK, CEP70, CEP63, PPM1K, MAP3K7, MPP6, COL4A5, HSP90AB1, SUGT1, STK11, PTGER3, FGFR1, ACTA2, ROR1"], [""], ["Regulation of actin cytoskeleton", "6.25", "CALD1, PLS3, FGF2, TAGLN, RHOB, CFL2, MYLK, ITGB5, WASL, JAK2, LMOD1, DSTN, PFN2, MYH11, ACTN1, PTPN11, SORBS1"]], "row_count": 12, "column_count": 3, "numeric_cells": 12, "header_rows": 1, "locator": "section[11]/table-wrap[1]#tab5"}}, {"id": "asset:table:pmid:29226137:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4d29e467aee22d84ede73d092e8de942f7c4b486902de598ed9b1c40fcaaf686", "bytes": 1675, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#tab6", "version": null, "note": "KEGG analysis based on module A.", "structure": {"pmcid": "PMC5684517", "section_index": 12, "section_title": "3.4. Pathways Interrelation Analysis", "row_count": 20, "column_count": 6}, "table": {"label": "Table 6", "caption": "KEGG analysis based on module A.", "rows": [["GOID", "GO term", "Ontology source", "Term P value", "Nr. genes", "Associated genes found"], ["GO:0004064", "NF-kappa B signaling pathway", "KEGG_01.03.2017", "19.0E − 6", "5.00", "[CCL19, CCL21, CXCL12, CXCL2, CXCL8]"], [""], ["GO:0005150", "Staphylococcus aureus infection", "KEGG_01.03.2017", "43.0E − 6", "4.00", "[C3, C3AR1, C5AR1, FPR3]"], [""], ["GO:0004060", "Cytokine-cytokine receptor interaction", "KEGG_01.03.2017", "37.0E − 18", "16.00", "[CCL16, CCL19, CCL20, CCL21, CCL5, CCR1, CCR2, CCR5, CCR7, CXCL1, CXCL12, CXCL16, CXCL2, CXCL3, CXCL8, CXCR4]"], [""], ["GO:0004062", "Chemokine signaling pathway", "KEGG_01.03.2017", "10.0E − 24", "18.00", "[ADCY3, ADCY4, CCL16, CCL19, CCL20, CCL21, CCL5, CCR1, CCR2, CCR5, CCR7, CXCL1, CXCL12, CXCL16, CXCL2, CXCL3, CXCL8, CXCR4]"], [""], ["GO:0004657", "IL-17 signaling pathway", "KEGG_01.03.2017", "17.0E − 6", "5.00", "[CCL20, CXCL1, CXCL2, CXCL3, CXCL8]"], [""], ["GO:0004668", "TNF signaling pathway", "KEGG_01.03.2017", "35.0E − 6", "5.00", "[CCL20, CCL5, CXCL1, CXCL2, CXCL3]"], [""], ["GO:0005120", "Epithelial cell signaling in Helicobacter pylori infection", "KEGG_01.03.2017", "1.7E − 3", "3.00", "[CCL5, CXCL1, CXCL8]"], [""], ["GO:0005132", "Salmonella infection", "KEGG_01.03.2017", "230.0E − 6", "4.00", "[CXCL1, CXCL2, CXCL3, CXCL8]"], [""], ["GO:0005134", "Legionellosis", "KEGG_01.03.2017", "1.2E − 6", "5.00", "[C3, CXCL1, CXCL2, CXCL3, CXCL8]"], [""], ["GO:0005323", "Rheumatoid arthritis", "KEGG_01.03.2017", "14.0E − 6", "5.00", "[CCL20, CCL5, CXCL1, CXCL12, CXCL8]"]], "row_count": 20, "column_count": 6, "numeric_cells": 47, "header_rows": 1, "locator": "section[12]/table-wrap[1]#tab6"}}, {"id": "asset:table:pmid:29226137:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:81733fc44f474872cae8e9576f379c4346bd392cf1da9fb9684fd8d858dfab3f", "bytes": 3079, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#tab7", "version": null, "note": "KEGG analysis based on module D.", "structure": {"pmcid": "PMC5684517", "section_index": 12, "section_title": "3.4. Pathways Interrelation Analysis", "row_count": 46, "column_count": 6}, "table": {"label": "Table 7", "caption": "KEGG analysis based on module D.", "rows": [["GOID", "GO term", "Ontology source", "Term P value", "Nr. genes", "Associated genes found"], ["GO:0005130", "Pathogenic Escherichia coli infection", "KEGG_01.03.2017", "3.6E − 3", "3.00", "[ABL1, RHOA, TUBA4A]"], [""], ["GO:0004071", "Sphingolipid signaling pathway", "KEGG_01.03.2017", "500.0E − 6", "5.00", "[PPP2CB, PPP2R5A, PPP2R5C, RAF1, RHOA]"], [""], ["GO:0004270", "Vascular smooth muscle contraction", "KEGG_01.03.2017", "570.0E − 6", "5.00", "[ACTG2, PPP1CB, PPP1R12A, RAF1, RHOA]"], [""], ["GO:0005210", "Colorectal cancer", "KEGG_01.03.2017", "4.6E − 3", "3.00", "[CYCS, RAF1, RHOA]"], [""], ["GO:0004270", "Vascular smooth muscle contraction", "KEGG_01.03.2017", "570.0E − 6", "5.00", "[ACTG2, PPP1CB, PPP1R12A, RAF1, RHOA]"], [""], ["GO:0004510", "Focal adhesion", "KEGG_01.03.2017", "560.0E − 12", "12.00", "[CCND2, EGFR, IGF1R, ITGB3, LAMA5, LAMC1, PPP1CB, PPP1R12A, RAF1, RHOA, TLN2, VCL]"], [""], ["GO:0004611", "Platelet activation", "KEGG_01.03.2017", "610.0E − 6", "5.00", "[ITGB3, PPP1CB, PPP1R12A, RHOA, TLN2]"], [""], ["GO:0004720", "Long-term potentiation", "KEGG_01.03.2017", "6.3E − 3", "3.00", "[PPP1CB, PPP3CB, RAF1]"], [""], ["GO:0004810", "Regulation of actin cytoskeleton", "KEGG_01.03.2017", "2.1E − 6", "9.00", "[EGFR, ENAH, ITGB3, PPP1CB, PPP1R12A, RAF1, RHOA, RRAS, VCL]"], [""], ["GO:0005210", "Colorectal cancer", "KEGG_01.03.2017", "4.6E − 3", "3.00", "[CYCS, RAF1, RHOA]"], [""], ["GO:0004071", "Sphingolipid signaling pathway", "KEGG_01.03.2017", "500.0E − 6", "5.00", "[PPP2CB, PPP2R5A, PPP2R5C, RAF1, RHOA]"], [""], ["GO:0004152", "AMPK signaling pathway", "KEGG_01.03.2017", "570.0E − 6", "5.00", "[IGF1R, PPP2CB, PPP2R5A, PPP2R5C, RHEB]"], [""], ["GO:0004520", "Adherens junction", "KEGG_01.03.2017", "700.0E − 6", "4.00", "[EGFR, IGF1R, RHOA, VCL]"], [""], ["GO:0004730", "Long-term depression", "KEGG_01.03.2017", "4.6E − 3", "3.00", "[IGF1R, PPP2CB, RAF1]"], [""], ["GO:0005214", "Glioma", "KEGG_01.03.2017", "5.6E − 3", "3.00", "[EGFR, IGF1R, RAF1]"], [""], ["GO:0005218", "Melanoma", "KEGG_01.03.2017", "6.9E − 3", "3.00", "[EGFR, IGF1R, RAF1]"], [""], ["GO:0003015", "mRNA surveillance pathway", "KEGG_01.03.2017", "10.0E − 6", "6.00", "[PAPOLA, PPP1CB, PPP2CB, PPP2R5A, PPP2R5C, SRRM1]"], [""], ["GO:0004071", "Sphingolipid signaling pathway", "KEGG_01.03.2017", "500.0E − 6", "5.00", "[PPP2CB, PPP2R5A, PPP2R5C, RAF1, RHOA]"], [""], ["GO:0004114", "Oocyte meiosis", "KEGG_01.03.2017", "63.0E − 6", "6.00", "[IGF1R, PPP1CB, PPP2CB, PPP2R5A, PPP2R5C, PPP3CB]"], [""], ["GO:0004152", "AMPK signaling pathway", "KEGG_01.03.2017", "570.0E − 6", "5.00", "[IGF1R, PPP2CB, PPP2R5A, PPP2R5C, RHEB]"], [""], ["GO:0004261", "Adrenergic signaling in cardiomyocytes", "KEGG_01.03.2017", "140.0E − 6", "6.00", "[PPP1CB, PPP2CB, PPP2R5A, PPP2R5C, TPM1, TPM2]"], [""], ["GO:0004730", "Long-term depression", "KEGG_01.03.2017", "4.6E − 3", "3.00", "[IGF1R, PPP2CB, RAF1]"], [""], ["GO:0005210", "Colorectal cancer", "KEGG_01.03.2017", "4.6E − 3", "3.00", "[CYCS, RAF1, RHOA]"]], "row_count": 46, "column_count": 6, "numeric_cells": 97, "header_rows": 1, "locator": "section[12]/table-wrap[2]#tab7"}}, {"id": "asset:table:pmid:29226137:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ca8c1dcb63a4001e98f3e6b25e8d37cfc8cfff2c2cb9564b10cb5f0222da7602", "bytes": 930, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#tab4", "version": null, "note": "KEGG pathways enrichment analysis in networks.", "structure": {"pmcid": "PMC5684517", "section_index": 13, "section_title": "4. Discussion", "row_count": 12, "column_count": 5}, "table": {"label": "Table 4", "caption": "KEGG pathways enrichment analysis in networks.", "rows": [["Expression", "#Pathway ID", "Pathway description", "Observed gene count", "False discovery rate"], ["Upregulated", "4380", "Osteoclast differentiation", "47", "6.30E − 22"], ["4060", "Cytokine-cytokine receptor interaction", "63", "6.90E − 18"], ["4062", "Chemokine signaling pathway", "51", "6.91E − 18"], ["4142", "Lysosome", "41", "1.75E − 17"], ["5150", "Staphylococcus aureus infection", "27", "2.52E − 17"], [""], ["Downregulated", "4510", "Focal adhesion", "38", "3.66E − 07"], ["4810", "Regulation of actin cytoskeleton", "37", "1.46E − 06"], ["5412", "Arrhythmogenic right ventricular cardiomyopathy (ARVC)", "20", "1.52E − 06"], ["4921", "Oxytocin signaling pathway", "30", "1.58E − 06"], ["4022", "cGMP-PKG signaling pathway", "30", "1.95E − 06"]], "row_count": 12, "column_count": 5, "numeric_cells": 30, "header_rows": 1, "locator": "section[13]/table-wrap[1]#tab4"}}], "gaps": ["asset:data:geo:GSE28829 not downloaded", "asset:data:geo:GSE28829 licence not read"]}, "analysis": {"state": "partial", "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"}}, {"id": "method-2", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "signal to noise method", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs were identified using signal to noise method where a total of 42,450 genes were analyzed and top 100 (top 100 upregulated and top 100 downregulated genes) genes were listed."}}], "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": ["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": ["GSE28829"], "resolved_accessions": ["GSE28829"], "statements": ["The gene expression profiles of GSE28829 were downloaded from Gene Expression Omnibus (GEO). GSE28829 was performed on GPL570, [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. The GSE28829 data set contained 29 samples, including 16 advanced atherosclerotic plaque samples and 13 early atherosclerotic plaque samples."], "basis": "The paper names GSE28829 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:29226137", "data:geo:GSE28829", "asset:table:pmid:29226137:1", "asset:table:pmid:29226137:2", "asset:table:pmid:29226137:3", "asset:table:pmid:29226137:4", "asset:table:pmid:29226137:5", "asset:table:pmid:29226137:6", "asset:table:pmid:29226137:7"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE28829"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:33:00Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 81275, "completion_tokens": 2704, "cached_tokens": 2064}}, "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:29226137", "type": "paper", "label": "pmid:29226137"}, {"id": "source:pmid:29226137", "type": "manuscript", "label": "PMID 29226137 full text"}, {"id": "data:geo:GSE28829", "type": "dataset", "label": "GEO GSE28829"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29226137", "type": "paper", "label": "pmid:29226137"}, {"id": "source:pmid:29226137", "type": "manuscript", "label": "PMID 29226137 full text"}, {"id": "data:geo:GSE28829", "type": "dataset", "label": "GEO GSE28829"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29226137", "type": "extraction", "used": ["source:pmid:29226137"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE28829", "type": "accession_resolution", "used": ["data:geo:GSE28829"], "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:29226137", "parent_hash": "sha256:f7294b575b035a00ff1dbc09ad549d301ba4bc6328e520fcf554918b9186b2f9", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE28829 licence not read", "asset:data:geo:GSE28829 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": "analysis_only", "id": "assay:1"}]}