Bioinformatics analysis of fibroblasts exposed to TGF‑β at the early proliferation phase of wound repair.

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The gene expression profiles of GSE79621 and GSE27165 were obtained from GEO database. Differentially expressed genes (DEGs) were identified using Morpheus and co‑expressed DEGs were selected using Venn Diagram. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. Protein‑protein interaction (PPI) networks of the DEGs were constructed using Cytoscape software. PPI interaction network was divided into subnetworks using the MCODE algorithm and the function of the top one module was analyzed using DAVID. The results revealed that upregulated DEGs were significantly enriched in biological process, including the Arp2/3 complex‑mediated actin nucleation, positive regulation of hyaluronan cable assembly, purine nucleobase biosynthetic process, de novo inosine monophosphate biosynthetic process, positive regulation of epithelial cell proliferation, whereas the downregulated DEGs were enriched in the regulation of blood pressure, negative regulation of cell proliferation, ossification, negative regulation of gene expression and type I interferon signaling pathway. KEGG pathway analysis showed that the upregulated DEGs were enriched in shigellosis, pathogenic Escherichia coli infection, the mitogen‑activated protein kinase signaling pathway, Ras signaling pathway and bacterial invasion of epithelial cells. The downregulated DEGs were enriched in systemic lupus erythematosus, lysosome, arachidonic acid metabolism, thyroid cancer and allograft rejection. The top 10 hub genes were identified from the PPI network. The top module analysis revealed that the included genes were involved in ion channel, neuroactive ligand‑receptor interaction pathway, purine metabolism and intestinal immune network for IgA production pathway. The functional analysis revealed that TGF‑β may promote fibroblast migration and proliferation and defend against microorganisms at the early proliferation stage of wound repair. Furthermore, these results may provide references for chronic wound repair.", "claims": [{"id": "claim-method", "statement": "The data was processed using web-based tool Morpheus (https://software.broadinstitute.org/morpheus/), which is a matrix visualization and analysis platform designed to support visual data exploration.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28983581", "locator": "sections[5] \"Identification of DEGs\" paragraph 2", "quote": "The data was processed using web-based tool Morpheus (https://software.broadinstitute.org/morpheus/), which is a matrix visualization and analysis platform designed to support visual data exploration."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Gene expression omnibus (GEO; www.ncbi.nlm.nih.gov/geo) contains original submitter-supplied records and curated DataSets, which is freely available to users. Two gene expression profiles (GSE79621 and GSE27165) were obtained from the GEO database. Data of fibroblast samples and TGF-β 24 h treated fibroblasts samples from the two gene expression profiles. The GSE79621 contained 3 fibroblast samples and 3TGF-β 24 h-treated fibroblast samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28983581", "locator": "sections[4] \"Microarray data\" paragraph 2", "quote": "Gene expression omnibus (GEO; www.ncbi.nlm.nih.gov/geo) contains original submitter-supplied records and curated DataSets, which is freely available to users. Two gene expression profiles (GSE79621 and GSE27165) were obtained from the GEO database. Data of fibroblast samples and TGF-β 24 h treated fibroblasts samples from the two gene expression profiles. 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Top 5 terms were selected according to P-value when more than five terms enriched terms were identified in each category.", "structure": {"pmcid": "PMC5779900", "section_index": 12, "section_title": "KEGG pathway analysis", "row_count": 17, "column_count": 5}, "table": {"label": "Table II.", "caption": "KEGG pathway analysis of upregulated and downregulated differentially expressed genes. 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"section[13]/table-wrap[1]#tIII-mmr-16-06-8146", "version": null, "note": "Degree of top 10 genes.", "structure": {"pmcid": "PMC5779900", "section_index": 13, "section_title": "PPI network construction and module analysis", "row_count": 11, "column_count": 4}, "table": {"label": "Table III.", "caption": "Degree of top 10 genes.", "rows": [["Gene ID", "Gene name", "Degree", "Expression"], ["GAPDH", "Glyceraldehyde-3-phosphate dehydrogenase", "83", "Upregulation"], ["MYC", "Myc proto-oncogene protein", "55", "Upregulation"], ["CDK1", "Cyclin-dependent kinase 1", "51", "Downregulation"], ["ACTB", "Actin, cytoplasmic 1", "50", "Upregulation"], ["APP", "Amyloid beta A4 protein", "40", "Downregulation"], ["PRKACB", "cAMP-dependent protein kinase catalytic subunit beta", "36", "Upregulation"], ["MAKP11", "Mitogen-activated protein kinase 11", "35", "Upregulation"], ["ACACB", "Acetyl-CoA carboxylase 2", "34", "Downregulation"], ["HSPA4", "Heat shock 70 kDa protein 4", "31", "Upregulation"], ["CAT", "Catalase", "31", "Downregulation"]], "row_count": 11, "column_count": 4, "numeric_cells": 17, "header_rows": 1, "locator": "section[13]/table-wrap[1]#tIII-mmr-16-06-8146"}}, {"id": "asset:table:pmid:28983581:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f8b102316a40b4d8f99ea68fcbc38f640dfd13c7d61eaf4a27028e72fd08d8e1", "bytes": 1012, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#tIV-mmr-16-06-8146", "version": null, "note": "Six modules from the protein-protein interaction network satisfied the criteria of MCODE scores ≥4 and number of nodes >4.", "structure": {"pmcid": "PMC5779900", "section_index": 13, "section_title": "PPI network construction and module analysis", "row_count": 7, "column_count": 5}, "table": {"label": "Table IV.", "caption": "Six modules from the protein-protein interaction network satisfied the criteria of MCODE scores ≥4 and number of nodes >4.", "rows": [["Cluster", "Score", "Nodes", "Edges", "Node IDs"], ["1", "6.353", "35", "108", "FXYD1, ANO1, FXYD3, CD34, POLR3A, GCH1, GNA14, CCR2, NME4, EDNRA, NME2, GUCY1A3, GUCY1A2, PTGER3, PROKR1, HDAC9, TNFSF13B, TUBA4A, DNAJC10, CCT3, GLRB, GLRA1, IARS, CLIC4, CXCL12, CXCR4, RAD51C, GRM7, F2R, RAD51, GAPDH, MKKS, APP, SAA1, ATF3"], ["2", "4.8", "6", "12", "MRAS, LRRC2, FMOD, RAP2C, MST4, PDE7B"], ["3", "4.5", "9", "18", "HLA-B, IRF4, GLDC, ACACB, OAS3, GART, PMPCB, IFIT3, HLA-C"], ["4", "4.5", "5", "9", "WDR4, CECR1, WDR12, PUS1, PUS7"], ["5", "4.3", "21", "43", "MYC, DHX9, MDM2, MCL1, VAMP1, YWHAG, RABL6, UPF2, STX16, TUBB, NUDT21, RAB6A, NSF, RPL37, RPL22, TUBB4Q, PHF5A, ACTB, VAMP4, STX6, AR"], ["6", "4", "4", "6", "COL6A2, COL13A1, COL4A4, COL11A1"]], "row_count": 7, "column_count": 5, "numeric_cells": 28, "header_rows": 1, "locator": "section[13]/table-wrap[2]#tIV-mmr-16-06-8146"}}, {"id": "asset:table:pmid:28983581:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:fff161b4992fad501e0c724cdd2ebb7367a659dd15d145f570b4c0dde20e3f2e", "bytes": 1508, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[3]#tV-mmr-16-06-8146", "version": null, "note": "Functional and pathway enrichment analysis of the genes in module. Top 3 terms were selected according to P-value when more than 3 terms enriched terms were identified in each category.", "structure": {"pmcid": "PMC5779900", "section_index": 13, "section_title": "PPI network construction and module analysis", "row_count": 22, "column_count": 5}, "table": {"label": "Table V.", "caption": "Functional and pathway enrichment analysis of the genes in module. Top 3 terms were selected according to P-value when more than 3 terms enriched terms were identified in each category.", "rows": [["A, Biological processes"], [""], ["Term", "Name", "Count", "P-value", "Genes"], ["GO:1902476", "Chloride transmembrane transport", "6", "1.15×10−6", "FXYD1, GLRB, FXYD3, GLRA1, CLIC4, ANO1"], ["GO:0006821", "Chloride transport", "5", "1.22×10−6", "FXYD1, FXYD3, GLRA1, CLIC4, ANO1"], ["GO:0007204", "Positive regulation of cytosolic calcium ion concentration", "6", "8.60×10−6", "EDNRA, PTGER3, CXCR4, SAA1, CCR2, F2R"], [""], ["B, Molecular functions"], [""], ["Term", "Name", "Count", "P-value", "Genes"], [""], ["GO:0005254", "Chloride channel activity", "4", "2.02×10−4", "FXYD1, FXYD3, CLIC4, ANO1"], ["GO:0005525", "GTP binding", "5", "0.007953298", "GNA14, GUCY1A2, GUCY1A3, TUBA4A, GCH1"], ["GO:0016934", "Extracellular-glycine-gated chloride channel activity", "2", "0.010379054", "GLRB, GLRA1"], [""], ["C, KEGG pathways"], [""], ["Term", "Name", "Count", "P-value", "Genes"], [""], ["hsa04080", "Neuroactive ligand-receptor interaction", "6", "0.003899897", "EDNRA, GLRB, PTGER3, GLRA1, GRM7, F2R"], ["hsa00230", "Purine metabolism", "5", "0.00451383", "NME4, NME2, GUCY1A2, GUCY1A3, POLR3A"], ["hsa04672", "Intestinal immune network for IgA production", "3", "0.014264846", "TNFSF13B, CXCR4, CXCL12"]], "row_count": 22, "column_count": 5, "numeric_cells": 29, "header_rows": 3, "locator": "section[13]/table-wrap[3]#tV-mmr-16-06-8146"}}], "gaps": ["asset:data:geo:GSE27165 not downloaded", "asset:data:geo:GSE27165 licence not read", "asset:data:geo:GSE79621 not downloaded", "asset:data:geo:GSE79621 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": "PPI"}}, {"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": "Morpheus", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The data was processed using web-based tool Morpheus (https://software.broadinstitute.org/morpheus/), which is a matrix visualization and analysis platform designed to support visual data exploration."}}], "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. 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