Bioinformatics prediction and analysis of hub genes and pathways of three types of gynecological cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31289534", "kind": "science-record", "revision": 8, "content_hash": "sha256:3907ca7b2dffb5c4f10bf42656a2098d21e84d19a46fe8d700d018d652ac34f6", "created_at": "2026-11-01T15:40:47Z", "updated_at": "2026-11-01T22:44:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics prediction and analysis of hub genes and pathways of three types of gynecological cancer.", "doi": "10.3892/ol.2019.10371", "pmid": "31289534", "authors": ["Yanyan Liu", "Yuexiong Yi", "Wanrong Wu", "Kejia Wu", "Wei Zhang"], "journal": "Oncology letters", "year": 2019, "abstract": "Cervical, endometrial and vulvar cancer are three common types of gynecological tumor that threaten the health of females worldwide. Since their underlying mechanisms and associations remain unclear, a comprehensive and systematic bioinformatics analysis is required. The present study downloaded GSE63678 from the GEO database and then performed functional enrichment analyses, including gene ontology and pathway analysis. To further investigate the molecular mechanisms underlying the three types of gynecological cancer, protein-protein interaction (PPI) analysis was performed. A biological network was generated with the guidance of the Kyoto Encyclopedia of Genes and Genomes database and was presented in Cytoscape. A total of 1,219 DEGs were identified for the three types of cancer, and 25 hub genes were revealed. Pathway analysis and the PPI network indicated that four main types of pathway participate in the mechanism of gynecological cancer, including viral infections and cancer formation, tumorigenesis and development, signal transduction, and endocrinology and metabolism. A preliminary gynecological cancer biological network was constructed. Notably, following all analysis, the phosphoinositide 3-kinase (PI3K)/Akt pathway was identified as a potential biomarker pathway. Seven pivotal hub genes (CCNA2, CDK1, CCND1, FGF2, IGF1, BCL2 and VEGFA) of the three gynecological cancer types were proposed. The seven hub genes may serve as targets in gynecological cancer for prevention and early intervention. The PI3K/Akt pathway was identified as a critical biomarker of the three types of gynecological cancer, which may serve a role in the pathogenesis. In summary, the present study provided evidence that could support the treatment of gynecologic tumors in the future.", "claims": [{"id": "claim-method", "statement": "Subsequently, the GEO2R (10) tool and limma package (11) available through Bioconductor (version 3.8) of R Studio (version 3.5) were used to compare the gene expression of the CC, EC and VC groups. P<0.05 and a fold-change >2 were considered to indicate a DEG.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31289534", "locator": "sections[5] \"Identification of DEGs\" paragraph 2", "quote": "Subsequently, the GEO2R (10) tool and limma package (11) available through Bioconductor (version 3.8) of R Studio (version 3.5) were used to compare the gene expression of the CC, EC and VC groups. P<0.05 and a fold-change >2 were considered to indicate a DEG."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31289534", "locator": "sections[23] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request."}], "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:31289534"], "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:GSE63678"], "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:GSE63678"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31289534", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3892/ol.2019.10371", "sha256": 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"structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1555075", "GSM1555076", "GSM1555077", "GSM1555078", "GSM1555079", "GSM1555080", "GSM1555081", "GSM1555082", "GSM1555083", "GSM1555084", "GSM1555085", "GSM1555086", "GSM1555087", "GSM1555088", "GSM1555089", "GSM1555090", "GSM1555091", "GSM1555092", "GSM1555093", "GSM1555094", "GSM1555095", "GSM1555096", "GSM1555097", "GSM1555098", "GSM1555099", "GSM1555100", "GSM1555101", "GSM1555102", "GSM1555103", "GSM1555104", "GSM1555105", "GSM1555106", "GSM1555107", "GSM1555108", "GSM1555109"], "sample_count": 35, "group_sizes": null, "group_sizes_basis": null, "platform": "571", "taxon": "Homo sapiens", "title": "Expression data from Vulvar, Cervical, Endometrial Carcinoma tissue", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:31289534:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1d54a4c1bbaf44a10ef2f324a0f436ec59d065cbfbc52d0def7092c7b61850b7", "bytes": 7242, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#tII-ol-0-0-10371", "version": null, "note": "Pathways enriched in three types of gynecological cancer.", "structure": {"pmcid": "PMC6539991", "section_index": 8, "section_title": "Pathway enrichment analysis of the hub genes", "row_count": 87, "column_count": 4}, "table": {"label": "Table II.", "caption": "Pathways enriched in three types of gynecological cancer.", "rows": [["Pathway", "Regulation", "P-value", "Genes in the pathway"], ["Viral carcinogenesis", "–", "3.43×10−9", "HIST1H2BD, CCND1, CDK1, HIST1H2BH, CDC20, PIK3R1, HIST1H2BK, CCNA2"], ["Hepatitis B", "–", "9.66×10−9", "BIRC5, CCND1, BCL2, PIK3R1, PCNA, CXCL8, CCNA2"], ["AMPK signaling pathway", "–", "1.13×10−7", "CCND1, PPP2R5C, IGF1, ACACB, PIK3R1, CCNA2"], ["Oocyte meiosis", "–", "1.31×10−7", "AURKA, PPP2R5C, IGF1, CDK1, CDC20, CCNB1"], ["Cell cycle", "Up", "1.31×10−7", "CCND1, CDK1, CDC20, PCNA, CCNA2, CCNB1"], ["EGFR tyrosine kinase inhibitor resistance", "–", "4.35×10−7", "FGF2, BCL2, IGF1, PIK3R1, VEGFA"], ["Pathways in cancer", "–", "6.44×10−7", "FGF2, BIRC5, CCND1, BCL2, IGF1, PIK3R1, CXCL8, VEGFA"], ["Progesterone-mediated oocyte maturation", "–", "1.15×10−6", "IGF1, CDK1, PIK3R1, CCNA2, CCNB1"], ["AGE-RAGE signaling pathway in diabetic complications", "–", "1.35×10−6", "CCND1, BCL2, PIK3R1, CXCL8, VEGFA"], ["HIF-1 signaling pathway", "–", "1.49×10−6", "BCL2, IGF1, GAPDH, PIK3R1, VEGFA"], ["Focal adhesion", "–", "2.13×10−6", "CCND1, BCL2, IGF1, FYN, PIK3R1, VEGFA"], ["PI3K-Akt signaling pathway", "–", "3.48×10−6", "FGF2, CCND1, BCL2, PPP2R5C, IGF1, PIK3R1, VEGFA"], ["p53 Signaling Pathway", "–", "3.94×10−6", "CCND1, BCL2, PCNA"], ["IL-7 Signal Transduction", "Down", "4.77×10−6", "BCL2, FYN, PIK3R1"], ["Colorectal cancer", "–", "5.72×10−6", "BIRC5, CCND1, BCL2, PIK3R1"], ["p53 signaling pathway", "–", "1.00×10−5", "CCND1, IGF1, CDK1, CCNB1"], ["Melanoma", "–", "1.00×10−5", "FGF2, CCND1, IGF1, PIK3R1"], ["Cyclins and Cell Cycle Regulation", "Up", "1.23×10−5", "CCND1, CDK1, CCNB1"], ["Platinum drug resistance", "–", "1.25×10−5", "BIRC5, BCL2, PIK3R1, TOP2A"], ["Regulation of BAD phosphorylation", "Down", "1.80×10−5", "BCL2, IGF1, PIK3R1"], ["Prostate cancer", "–", "2.52×10−5", "CCND1, BCL2, IGF1, PIK3R1"], ["Endocrine resistance", "–", "3.71×10−5", "CCND1, BCL2, IGF1, PIK3R1"], ["Proteoglycans in cancer", "–", "4.47×10−5", "FGF2, CCND1, IGF1, PIK3R1, VEGFA"], ["Bladder cancer", "Up", "7.25×10−5", "CCND1, CXCL8, VEGFA"], ["Sphingolipid signaling pathway", "–", "8.32×10−5", "BCL2, PPP2R5C, FYN, PIK3R1"], ["FoxO signaling pathway", "–", "1.29×10−4", "CCND1, IGF1, PIK3R1, CCNB1"], ["Systemic lupus erythematosus", "Up", "1.32×10−4", "H2AFZ, HIST1H2BD, HIST1H2BH, HIST1H2BK"], ["NFAT and Hypertrophy of the heart (Transcription in the broken heart)", "Down", "1.66×10−4", "FGF2, IGF1, PIK3R1"], ["Breast cancer", "–", "1.80×10−4", "FGF2, CCND1, IGF1, PIK3R1"], ["Activation of Src by Protein-tyrosine phosphatase alpha", "Up", "2.11×10−4", "CDK1, CCNB1"], ["Sonic Hedgehog (SHH) Receptor Ptc1 Regulates cell cycle", "Up", "2.11×10−4", "CDK1, CCNB1"], ["AKAP95 role in mitosis and chromosome dynamics", "Up", "2.52×10−4", "CDK1, CCNB1"], ["Glioma", "–", "2.75×10−4", "CCND1, IGF1, PIK3R1"], ["Pancreatic cancer", "–", "2.75×10−4", "CCND1, PIK3R1, VEGFA"], ["Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases.", "Up", "2.98×10−4", "CCND1, CCNA2"], ["The IGF-1 Receptor and Longevity", "Down", "4.00×10−4", "IGF1, PIK3R1"], ["Alcoholism", "Up", "4.22×10−4", "H2AFZ, HIST1H2BD, HIST1H2BH, HIST1H2BK"], ["B Cell Survival Pathway", "–", "4.57×10−4", "BIRC5, PIK3R1"], ["Small cell lung cancer", "–", "6.12×10−4", "CCND1, BCL2, PIK3R1"], ["Stathmin and breast cancer resistance to antimicrotubule agents", "Up", "6.48×10−4", "CDK1, CCNB1"], ["Epstein-Barr virus infection", "–", "6.64×10−4", "BCL2, CDK1, PIK3R1, CCNA2"], ["Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway", "Down", "7.19×10−4", "IGF1, PIK3R1"], ["Rap1 signaling pathway", "–", "7.54×10−4", "FGF2, IGF1, PIK3R1, VEGFA"], ["IGF-1 Signaling Pathway", "Down", "7.94×10−4", "IGF1, PIK3R1"], ["Ras signaling pathway", "–", "1.01×10−3", "FGF2, IGF1, PIK3R1, VEGFA"], ["Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia", "Down", "1.04×10−3", "FYN, PIK3R1"], ["Cell Cycle: G2/M Checkpoint", "Up", "1.04×10−3", "CDK1, CCNB1"], ["Influence of Ras and Rho proteins on G1 to S Transition", "–", "1.22×10−3", "CCND1, PIK3R1"], ["Genes related to IL4 rceptor signaling in B lymphocytes", "Down", "1.32×10−3", "BCL2, PIK3R1"], ["Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages", "Up", "1.32×10−3", "CCND1, PIK3R1"], ["Cholinergic synapse", "Down", "1.41×10−3", "BCL2, FYN, PIK3R1"], ["Cell Cycle: G1/S Check Point", "Up", "1.42×10−3", "CCND1, CDK1"], ["VEGF, Hypoxia, and Angiogenesis", "–", "1.52×10−3", "PIK3R1, VEGFA"], ["HTLV–I infection", "–", "1.57×10−3", "CCND1, CDC20, PIK3R1, PCNA"], ["Control of skeletal myogenesis by HDAC and calcium/calmodulin-dependent kinase (CaMK)", "Down", "1.63×10−3", "IGF1, PIK3R1"], ["Apoptosis-multiple species", "–", "1.97×10−3", "BIRC5, BCL2"], ["How Progesterone Initiates Oocyte Membrane", "Up", "2.09×10−3", "CDK1, CCNB1"], ["Measles", "–", "2.36×10−3", "CCND1, FYN, PIK3R1"], ["Aldosterone-regulated sodium reabsorption", "Down", "2.47×10−3", "IGF1, PIK3R1"], ["Apoptosis", "–", "2.56×10−3", "BIRC5, BCL2, PIK3R1"], ["IL-2 Receptor Beta Chain in T cell Activation", "Down", "2.60×10−3", "BCL2, PIK3R1"], ["Signaling pathways regulating pluripotency of stem cells", "Down", "2.62×10−3", "FGF2, IGF1, PIK3R1"], ["Fluid shear stress and atherosclerosis", "–", "2.78×10−3", "BCL2, PIK3R1, VEGFA"], ["Phospholipase D signaling pathway", "–", "3.01×10−3", "FYN, PIK3R1, CXCL8"], ["Jak-STAT signaling pathway", "–", "3.63×10−3", "CCND1, BCL2, PIK3R1"], ["Members of the BCR signaling pathway", "Down", "3.80×10−3", "BCL2, PIK3R1"], ["Hedgehog signaling pathway", "–", "3.96×10−3", "CCND1, BCL2"], ["T Cell Receptor Signaling Pathway", "Down", "3.96×10−3", "FYN, PIK3R1"], ["Endometrial cancer", "–", "4.47×10−3", "CCND1, PIK3R1"], ["Genes encoding secreted soluble factors", "–", "4.58×10−3", "FGF2, IGF1, CXCL8, VEGFA"], ["Acute myeloid leukemia", "–", "5.39×10−3", "CCND1, PIK3R1"], ["Non-small cell lung cancer", "–", "5.97×10−3", "CCND1, PIK3R1"], ["VEGF signaling pathway", "–", "6.18×10−3", "PIK3R1, VEGFA"], ["Viral myocarditis", "–", "6.18×10−3", "CCND1, FYN"], ["Longevity regulating pathway-multiple species", "Down", "6.80×10−3", "IGF1, PIK3R1"], ["Renal cell carcinoma", "–", "7.45×10−3", "PIK3R1, VEGFA"], ["Fc epsilon RI signaling pathway", "–", "8.13×10−3", "FYN, PIK3R1"], ["Prolactin signaling pathway", "–", "8.60×10−3", "CCND1, PIK3R1"], ["Chronic myeloid leukemia", "–", "8.84×10−3", "CCND1, PIK3R1"], ["Longevity regulating pathway", "–", "1.36×10−2", "IGF1, PIK3R1"], ["Genes related to Wnt-mediated signal transduction", "Up", "1.36×10−2", "CCND1, GAPDH"], ["Rheumatoid arthritis", "Up", "1.39×10−2", "CXCL8, VEGFA"], ["NF-kappa B signaling pathway", "–", "1.54×10−2", "BCL2, CXCL8"], ["Amoebiasis", "–", "1.57×10−2", "PIK3R1, CXCL8"], ["Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition.", "Up", "1.60×10−2", "CDK1"], ["Inflammatory mediator regulation of TRP channels", "Down", "1.60×10−2", "IGF1, PIK3R1"]], "row_count": 87, "column_count": 4, "numeric_cells": 100, "header_rows": 1, "locator": "section[16]/table-wrap[1]#tII-ol-0-0-10371"}}, {"id": "asset:table:pmid:31289534:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:85d8c2990d39974133b6b8ec97e3b3308a1e53b8a7633ab612ad78c6a62ae41f", "bytes": 1700, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#tI-ol-0-0-10371", "version": null, "note": "Topological parameters of the hub genes.", "structure": {"pmcid": "PMC6539991", "section_index": 14, "section_title": "Hub genes and PPI network", "row_count": 27, "column_count": 6}, "table": {"label": "Table I.", "caption": "Topological parameters of the hub genes.", "rows": [["Gene", "Degree", "Betweeness", "Closeness", "Group", "Regulation"], ["Mean", "13", "2081.81034", "3.73×10−4", "–", "–"], ["CDK1", "115", "20448.4838", "5.21×10−4", "CC/EC", "Up"], ["CCNB1", "100", "16335.9142", "5.23×10−4", "CC/EC", "Up"], ["CDC20", "92", "8148.54809", "4.76×10−4", "EC", "Up"], ["CCNA2", "91", "8126.90458", "4.89×10−4", "CC/EC/VC", "Up"], ["AURKA", "90", "9181.94344", "4.76×10−4", "EC/VC", "Up"], ["TOP2A", "87", "21409.6376", "5.15×10−4", "EC/VC", "Up"], ["UBE2C", "82", "14916.6491", "4.82×10−4", "EC/VC", "Up"], ["BIRC5", "80", "16279.0157", "5.13×10−4", "EC/VC", "Up"], ["PCNA", "62", "26080.2036", "5.25×10−4", "CC/EC", "Up"], ["VEGFA", "56", "32712.0335", "5.43×10−4", "VC", "Up"], ["PIK3R1", "46", "24576.8505", "4.91×10−4", "VC", "Down"], ["HIST1H2BK", "43", "8689.20717", "4.70×10−4", "CC/VC", "Up"], ["HIST1H2BD", "43", "8689.20717", "4.70×10−4", "VC", "Up"], ["HIST1H2BH", "42", "8291.98846", "4.70×10−4", "VC", "Up"], ["ACACB", "41", "40853.547", "4.98×10−4", "VC", "Down"], ["CXCL8", "40", "28927.396", "5.16×10−4", "VC", "Up"], ["H2AFZ", "39", "8793.56814", "4.67×10−4", "CC", "Up"], ["IGF1", "38", "16278.2011", "5.07×10−4", "CC/VC", "Down"], ["ACLY", "37", "34157.4527", "4.81×10−4", "EC", "Up"], ["CCND1", "36", "28548.907", "5.39×10−4", "EC", "Up"], ["GAPDH", "33", "41598.1258", "5.39×10−4", "EC", "Up"], ["PPP2R5C", "32", "10238.8057", "4.75×10−4", "CC", "UP"], ["FYN", "32", "17254.3572", "5.22×10−4", "CC/VC", "Down"], ["FGF2", "32", "19465.3169", "5.20×10−4", "EC", "Down"], ["BCL2", "32", "17923.6004", "4.86×10−4", "VC", "Down"]], "row_count": 27, "column_count": 6, "numeric_cells": 79, "header_rows": 1, "locator": "section[14]/table-wrap[1]#tI-ol-0-0-10371"}}, {"id": "asset:table:pmid:31289534:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1d54a4c1bbaf44a10ef2f324a0f436ec59d065cbfbc52d0def7092c7b61850b7", "bytes": 7242, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#tII-ol-0-0-10371", "version": null, "note": "Pathways enriched in three types of gynecological cancer.", "structure": {"pmcid": "PMC6539991", "section_index": 16, "section_title": "Pathway enrichment analysis of the hub genes", "row_count": 87, "column_count": 4}, "table": {"label": "Table II.", "caption": "Pathways enriched in three types of gynecological cancer.", "rows": [["Pathway", "Regulation", "P-value", "Genes in the pathway"], ["Viral carcinogenesis", "–", "3.43×10−9", "HIST1H2BD, CCND1, CDK1, HIST1H2BH, CDC20, PIK3R1, HIST1H2BK, CCNA2"], ["Hepatitis B", "–", "9.66×10−9", "BIRC5, CCND1, BCL2, PIK3R1, PCNA, CXCL8, CCNA2"], ["AMPK signaling pathway", "–", "1.13×10−7", "CCND1, PPP2R5C, IGF1, ACACB, PIK3R1, CCNA2"], ["Oocyte meiosis", "–", "1.31×10−7", "AURKA, PPP2R5C, IGF1, CDK1, CDC20, CCNB1"], ["Cell cycle", "Up", "1.31×10−7", "CCND1, CDK1, CDC20, PCNA, CCNA2, CCNB1"], ["EGFR tyrosine kinase inhibitor resistance", "–", "4.35×10−7", "FGF2, BCL2, IGF1, PIK3R1, VEGFA"], ["Pathways in cancer", "–", "6.44×10−7", "FGF2, BIRC5, CCND1, BCL2, IGF1, PIK3R1, CXCL8, VEGFA"], ["Progesterone-mediated oocyte maturation", "–", "1.15×10−6", "IGF1, CDK1, PIK3R1, CCNA2, CCNB1"], ["AGE-RAGE signaling pathway in diabetic complications", "–", "1.35×10−6", "CCND1, BCL2, PIK3R1, CXCL8, VEGFA"], ["HIF-1 signaling pathway", "–", "1.49×10−6", "BCL2, IGF1, GAPDH, PIK3R1, VEGFA"], ["Focal adhesion", "–", "2.13×10−6", "CCND1, BCL2, IGF1, FYN, PIK3R1, VEGFA"], ["PI3K-Akt signaling pathway", "–", "3.48×10−6", "FGF2, CCND1, BCL2, PPP2R5C, IGF1, PIK3R1, VEGFA"], ["p53 Signaling Pathway", "–", "3.94×10−6", "CCND1, BCL2, PCNA"], ["IL-7 Signal Transduction", "Down", "4.77×10−6", "BCL2, FYN, PIK3R1"], ["Colorectal cancer", "–", "5.72×10−6", "BIRC5, CCND1, BCL2, PIK3R1"], ["p53 signaling pathway", "–", "1.00×10−5", "CCND1, IGF1, CDK1, CCNB1"], ["Melanoma", "–", "1.00×10−5", "FGF2, CCND1, IGF1, PIK3R1"], ["Cyclins and Cell Cycle Regulation", "Up", "1.23×10−5", "CCND1, CDK1, CCNB1"], ["Platinum drug resistance", "–", "1.25×10−5", "BIRC5, BCL2, PIK3R1, TOP2A"], ["Regulation of BAD phosphorylation", "Down", "1.80×10−5", "BCL2, IGF1, PIK3R1"], ["Prostate cancer", "–", "2.52×10−5", "CCND1, BCL2, IGF1, PIK3R1"], ["Endocrine resistance", "–", "3.71×10−5", "CCND1, BCL2, IGF1, PIK3R1"], ["Proteoglycans in cancer", "–", "4.47×10−5", "FGF2, CCND1, IGF1, PIK3R1, VEGFA"], ["Bladder cancer", "Up", "7.25×10−5", "CCND1, CXCL8, VEGFA"], ["Sphingolipid signaling pathway", "–", "8.32×10−5", "BCL2, PPP2R5C, FYN, PIK3R1"], ["FoxO signaling pathway", "–", "1.29×10−4", "CCND1, IGF1, PIK3R1, CCNB1"], ["Systemic lupus erythematosus", "Up", "1.32×10−4", "H2AFZ, HIST1H2BD, HIST1H2BH, HIST1H2BK"], ["NFAT and Hypertrophy of the heart (Transcription in the broken heart)", "Down", "1.66×10−4", "FGF2, IGF1, PIK3R1"], ["Breast cancer", "–", "1.80×10−4", "FGF2, CCND1, IGF1, PIK3R1"], ["Activation of Src by Protein-tyrosine phosphatase alpha", "Up", "2.11×10−4", "CDK1, CCNB1"], ["Sonic Hedgehog (SHH) Receptor Ptc1 Regulates cell cycle", "Up", "2.11×10−4", "CDK1, CCNB1"], ["AKAP95 role in mitosis and chromosome dynamics", "Up", "2.52×10−4", "CDK1, CCNB1"], ["Glioma", "–", "2.75×10−4", "CCND1, IGF1, PIK3R1"], ["Pancreatic cancer", "–", "2.75×10−4", "CCND1, PIK3R1, VEGFA"], ["Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases.", "Up", "2.98×10−4", "CCND1, CCNA2"], ["The IGF-1 Receptor and Longevity", "Down", "4.00×10−4", "IGF1, PIK3R1"], ["Alcoholism", "Up", "4.22×10−4", "H2AFZ, HIST1H2BD, HIST1H2BH, HIST1H2BK"], ["B Cell Survival Pathway", "–", "4.57×10−4", "BIRC5, PIK3R1"], ["Small cell lung cancer", "–", "6.12×10−4", "CCND1, BCL2, PIK3R1"], ["Stathmin and breast cancer resistance to antimicrotubule agents", "Up", "6.48×10−4", "CDK1, CCNB1"], ["Epstein-Barr virus infection", "–", "6.64×10−4", "BCL2, CDK1, PIK3R1, CCNA2"], ["Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway", "Down", "7.19×10−4", "IGF1, PIK3R1"], ["Rap1 signaling pathway", "–", "7.54×10−4", "FGF2, IGF1, PIK3R1, VEGFA"], ["IGF-1 Signaling Pathway", "Down", "7.94×10−4", "IGF1, PIK3R1"], ["Ras signaling pathway", "–", "1.01×10−3", "FGF2, IGF1, PIK3R1, VEGFA"], ["Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia", "Down", "1.04×10−3", "FYN, PIK3R1"], ["Cell Cycle: G2/M Checkpoint", "Up", "1.04×10−3", "CDK1, CCNB1"], ["Influence of Ras and Rho proteins on G1 to S Transition", "–", "1.22×10−3", "CCND1, PIK3R1"], ["Genes related to IL4 rceptor signaling in B lymphocytes", "Down", "1.32×10−3", "BCL2, PIK3R1"], ["Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages", "Up", "1.32×10−3", "CCND1, PIK3R1"], ["Cholinergic synapse", "Down", "1.41×10−3", "BCL2, FYN, PIK3R1"], ["Cell Cycle: G1/S Check Point", "Up", "1.42×10−3", "CCND1, CDK1"], ["VEGF, Hypoxia, and Angiogenesis", "–", "1.52×10−3", "PIK3R1, VEGFA"], ["HTLV–I infection", "–", "1.57×10−3", "CCND1, CDC20, PIK3R1, PCNA"], ["Control of skeletal myogenesis by HDAC and calcium/calmodulin-dependent kinase (CaMK)", "Down", "1.63×10−3", "IGF1, PIK3R1"], ["Apoptosis-multiple species", "–", "1.97×10−3", "BIRC5, BCL2"], ["How Progesterone Initiates Oocyte Membrane", "Up", "2.09×10−3", "CDK1, CCNB1"], ["Measles", "–", "2.36×10−3", "CCND1, FYN, PIK3R1"], ["Aldosterone-regulated sodium reabsorption", "Down", "2.47×10−3", "IGF1, PIK3R1"], ["Apoptosis", "–", "2.56×10−3", "BIRC5, BCL2, PIK3R1"], ["IL-2 Receptor Beta Chain in T cell Activation", "Down", "2.60×10−3", "BCL2, PIK3R1"], ["Signaling pathways regulating pluripotency of stem cells", "Down", "2.62×10−3", "FGF2, IGF1, PIK3R1"], ["Fluid shear stress and atherosclerosis", "–", "2.78×10−3", "BCL2, PIK3R1, VEGFA"], ["Phospholipase D signaling pathway", "–", "3.01×10−3", "FYN, PIK3R1, CXCL8"], ["Jak-STAT signaling pathway", "–", "3.63×10−3", "CCND1, BCL2, PIK3R1"], ["Members of the BCR signaling pathway", "Down", "3.80×10−3", "BCL2, PIK3R1"], ["Hedgehog signaling pathway", "–", "3.96×10−3", "CCND1, BCL2"], ["T Cell Receptor Signaling Pathway", "Down", "3.96×10−3", "FYN, PIK3R1"], ["Endometrial cancer", "–", "4.47×10−3", "CCND1, PIK3R1"], ["Genes encoding secreted soluble factors", "–", "4.58×10−3", "FGF2, IGF1, CXCL8, VEGFA"], ["Acute myeloid leukemia", "–", "5.39×10−3", "CCND1, PIK3R1"], ["Non-small cell lung cancer", "–", "5.97×10−3", "CCND1, PIK3R1"], ["VEGF signaling pathway", "–", "6.18×10−3", "PIK3R1, VEGFA"], ["Viral myocarditis", "–", "6.18×10−3", "CCND1, FYN"], ["Longevity regulating pathway-multiple species", "Down", "6.80×10−3", "IGF1, PIK3R1"], ["Renal cell carcinoma", "–", "7.45×10−3", "PIK3R1, VEGFA"], ["Fc epsilon RI signaling pathway", "–", "8.13×10−3", "FYN, PIK3R1"], ["Prolactin signaling pathway", "–", "8.60×10−3", "CCND1, PIK3R1"], ["Chronic myeloid leukemia", "–", "8.84×10−3", "CCND1, PIK3R1"], ["Longevity regulating pathway", "–", "1.36×10−2", "IGF1, PIK3R1"], ["Genes related to Wnt-mediated signal transduction", "Up", "1.36×10−2", "CCND1, GAPDH"], ["Rheumatoid arthritis", "Up", "1.39×10−2", "CXCL8, VEGFA"], ["NF-kappa B signaling pathway", "–", "1.54×10−2", "BCL2, CXCL8"], ["Amoebiasis", "–", "1.57×10−2", "PIK3R1, CXCL8"], ["Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition.", "Up", "1.60×10−2", "CDK1"], ["Inflammatory mediator regulation of TRP channels", "Down", "1.60×10−2", "IGF1, PIK3R1"]], "row_count": 87, "column_count": 4, "numeric_cells": 100, "header_rows": 1, "locator": "section[16]/table-wrap[1]#tII-ol-0-0-10371"}}], "gaps": ["asset:data:geo:GSE63678 not downloaded", "asset:data:geo:GSE63678 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Subsequently, the GEO2R (10) tool and limma package (11) available through Bioconductor (version 3.8) of R Studio (version 3.5) were used to compare the gene expression of the CC, EC and VC groups. P<0.05 and a fold-change >2 were considered to indicate a DEG."}}, {"id": "method-2", "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-3", "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": 0.8, "band": "high", "quote": "GO enrichment"}}], "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE63678"], "resolved_accessions": ["GSE63678"], "statements": ["The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE63678 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:31289534", "data:geo:GSE63678", "asset:table:pmid:31289534:1", "asset:table:pmid:31289534:2", "asset:table:pmid:31289534:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE63678"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:15:24Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 37083, "completion_tokens": 937, "cached_tokens": 785}}, "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:31289534", "type": "paper", "label": "pmid:31289534"}, {"id": "source:pmid:31289534", "type": "manuscript", "label": "PMID 31289534 full text"}, {"id": "data:geo:GSE63678", "type": "dataset", "label": "GEO GSE63678"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:31289534", "type": "paper", "label": "pmid:31289534"}, {"id": "source:pmid:31289534", "type": "manuscript", "label": "PMID 31289534 full text"}, {"id": "data:geo:GSE63678", "type": "dataset", "label": "GEO GSE63678"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-31289534", "type": "extraction", "used": ["source:pmid:31289534"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE63678", "type": "accession_resolution", "used": ["data:geo:GSE63678"], "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:31289534", "parent_hash": "sha256:744397fa4cb82d4339305af6bf26314d549136040890aa674e9047447e9938f7", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE63678 licence not read", "asset:data:geo:GSE63678 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Subsequently, the GEO2R (10) tool and limma package (11) available through Bioconductor (version 3.8) of R Studio (version 3.5) were used to compare the gene expression of the CC, EC and VC groups. P<0.05 and a fold-change >2 were considered to indicate a DEG."], "order_basis": "analysis_only", "id": "assay:1"}]}