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pmid:32669126
Identification of candidate biomarkers and pathways associated with psoriasis using bioinformatics analysis.
Yongqi Luo · Yangyang Luo · Jing Chang · Zhenghui Xiao · Bin Zhou
Hereditas · 2020 doi:10.1186/s41065-020-00141-1
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Complete file
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Then the differentially expressed genes (DEGs) with |logFC| > 2 and adjusted P < 0.05 were chosen. In addition, the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for DEGs were performed. Then, the GO terms with P < 0.05 and overlap coefficient greater than 0.5 were integrated by EnrichmentMap. Additionally, risk subpathways analysis for DEGs was also conducted by using the iSubpathwayMiner package to obtain more psoriasis-related DEGs and pathways. Finally, protein-protein interaction (PPI) network analysis was performed to identify the hub genes, and the DGIdb database was utilized to search for the candidate drugs for psoriasis.\nRESULTS: A total of 127 DEGs which were mostly associated with keratinization, keratinocyte differentiation, and epidermal cell differentiation biological processes were identified. Based on these GO terms, 3 modules (human skin, epidermis and cuticle differentiation, and enzyme activity) were constructed. Moreover, 9 risk subpathways such as steroid hormone biosynthesis, folate biosynthesis, and pyrimidine metabolism were screened. Finally, PPI network analysis demonstrated that CXCL10 was the hub gene with the highest degree, and CXCR2, CXCL10, IVL, OASL, and ISG15 were the potential gene targets of the drugs for treating psoriasis.\nCONCLUSION: Psoriasis may be mostly caused by keratinization, keratinocyte differentiation, and epidermal cell differentiation; the pathogeneses were more related with pathways such as steroid hormone biosynthesis, folate biosynthesis, and pyrimidine metabolism. Besides, some psoriasis-related genes such as SPRR genes, HSD11B1, GGH, CXCR2, IVL, OASL, ISG15, and CXCL10 may be important targets in psoriatic therapy.", "claims": [{"id": "claim-method", "statement": "After data preprocessing, the limma package [31] of R language was utilized to screen DEGs. 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differentially expressed genes (DEGs) in gene expression profile of psoriatic patients (P < 0.05)", "rows": [["ID", "Name", "Pvalue", "DEGs"], ["GO:0031424", "Keratinization", "6.15E-10", "SPRR2C, SPRR1A, SPRR1B, LCE3D, TGM1, CNFN, SPRR3, TGM3, SPRR2G, IVL"], ["GO:0030216", "Keratinocyte differentiation", "9.07E-10", "SPRR2C, S100A7, SPRR1A, SPRR1B, LCE3D, TGM1, CNFN, SPRR3, TGM3, SPRR2G, IVL"], ["GO:0009913", "Epidermal cell differentiation", "2.01E-09", "SPRR2C, S100A7, SPRR1A, SPRR1B, LCE3D, TGM1, CNFN, SPRR3, TGM3, SPRR2G, IVL"], ["GO:0007398", "Ectoderm development", "1.76E-08", "KRT6A, S100A7, LCE3D, SPRR2G, SPRR2C, KRT16, SPRR1A, SPRR1B, CNFN, TGM1, SPRR3, TGM3, ALOX12B, IVL"], ["GO:0030855", "Epithelial cell differentiation", "4.85E-08", "RHCG, SPRR2C, S100A7, SPRR1A, SPRR1B, LCE3D, TGM1, CNFN, SPRR3, TGM3, SPRR2G, IVL"], ["GO:0006952", "Defense response", "5.96E-08", "CXCL1, DCD, KYNU, IL8, S100A8, S100A7, S100A9, CXCL9, RSAD2, CXCR2, CCL18, S100A12, CXCL10, WFDC12, FOS, 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differentially expressed genes (DEGs) in psoriatic patients (P < 0.05)", "rows": [["ID", "Name", "Pvalue", "DEGs"], ["Path:00140_13", "Steroid hormone biosynthesis", "0.01561", "HSD11B1"], ["Path:00790_4", "Folate biosynthesis", "0.01561", "GGH"], ["Path:00240_21", "Pyrimidine metabolism", "0.019471", "CMPK2, RRM2"], ["Path:00240_16", "Pyrimidine metabolism", "0.030339", "CMPK2, RRM2"], ["Path:00531_3", "Glycosaminoglycan degradation", "0.041091", "HYAL4"], ["Path:00240_12", "Pyrimidine metabolism", "0.044307", "CMPK2, RRM2"], ["Path:00140_18", "Steroid hormone biosynthesis", "0.046108", "HSD11B1"], ["Path:00380_10", "Tryptophan metabolism", "0.046108", "KYNU"], ["Path:00480_6", "Glutathione metabolism", "0.046108", "RRM2"]], "row_count": 10, "column_count": 4, "numeric_cells": 20, "header_rows": 1, "locator": "section[6]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:32669126:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:acaaf17bb54aebb4afa54e67bc64b76179bdda331ec85945963a761deb91a1fc", "bytes": 530, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[1]#Tab4", "version": null, "note": "Top 16 proteins of the higher degrees in protein-protein interaction (PPI) network of differentially expressed genes (DEGs)", "structure": {"pmcid": "PMC7364515", "section_index": 7, "section_title": "Construction of protein-protein interaction network based on differentially expressed genes", "row_count": 17, "column_count": 2}, "table": {"label": "Table 4", "caption": "Top 16 proteins of the higher degrees in protein-protein interaction (PPI) network of differentially expressed genes (DEGs)", "rows": [["Proteins", "Degree"], ["CXCL10", "20"], ["STAT1", "15"], ["CXCL1", "13"], ["CXCL9", "12"], ["IRF7", "12"], ["IVL", "12"], ["MX1", "12"], ["S100A9", "12"], ["CXCR2", "11"], ["ISG15", "11"], ["OAS1", "11"], ["OASL", "11"], ["RSAD2", "11"], ["RTP4", "11"], ["SPRR1B", "11"], ["CMPK2", "10"]], "row_count": 17, "column_count": 2, "numeric_cells": 19, "header_rows": 1, "locator": "section[7]/table-wrap[1]#Tab4"}}, {"id": "asset:table:pmid:32669126:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b0d2c8f1f285284f4bf692d45161b6ee2d9d5d0afb0585e405072b207d98e908", "bytes": 2448, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#Tab5", "version": null, "note": "Candidate drugs targeting hub genes", "structure": {"pmcid": "PMC7364515", "section_index": 8, "section_title": "Drug-hub gene interaction", "row_count": 37, "column_count": 5}, "table": {"label": "Table 5", "caption": "Candidate drugs targeting hub genes", "rows": [["gene", "drug", "interaction_types", "sources", "pmids"], ["CXCR2", "PROPOFOL", "agonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "BENZPIPERYLON", "agonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "CHEMBL411250", "agonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "MEPHENTERMINE", "agonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "REPARIXIN", "allosteric modulator|modulator|antagonist", "GuideToPharmacologyInteractions|ChemblInteractions|TTD", "–"], ["CXCR2", "DANIRIXIN", "antagonist", "GuideToPharmacologyInteractions|ChemblInteractions", "–"], ["CXCR2", "NAVARIXIN", "antagonist", "GuideToPharmacologyInteractions|ChemblInteractions|TTD", "–"], ["CXCR2", "CHEMBL239767", "antagonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "NAVARIXIN HYDRATE", "antagonist", "ChemblInteractions", "–"], ["CXCR2", "ELUBRIXIN", "antagonist", "ChemblInteractions|TTD", "–"], ["CXCR2", "Ladarixin", "modulator", "ChemblInteractions", "–"], ["CXCR2", "BEVACIZUMAB", "–", "PharmGKB", "–"], ["CXCR2", "CYCLOPHOSPHAMIDE", "–", "PharmGKB", "–"], ["CXCR2", "ACETYLCYSTEINE", "–", "NCI", 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"TdgClinicalTrial", "–"], ["CXCL10", "STAVUDINE", "–", "NCI", "11,141,242"], ["CXCL10", "GONADOTROPIN, CHORIONIC", "–", "NCI", "15,590,984"], ["CXCL10", "RITONAVIR", "–", "NCI", "11,141,242"], ["CXCL10", "ATORVASTATIN", "–", "NCI", "10,559,511"]], "row_count": 37, "column_count": 5, "numeric_cells": 36, "header_rows": 1, "locator": "section[8]/table-wrap[1]#Tab5"}}, {"id": "asset:table:pmid:32669126:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b0d2c8f1f285284f4bf692d45161b6ee2d9d5d0afb0585e405072b207d98e908", "bytes": 2448, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#Tab5", "version": null, "note": "Candidate drugs targeting hub genes", "structure": {"pmcid": "PMC7364515", "section_index": 18, "section_title": "Drug-hub gene interaction", "row_count": 37, "column_count": 5}, "table": {"label": "Table 5", "caption": "Candidate drugs targeting hub genes", "rows": [["gene", "drug", "interaction_types", "sources", "pmids"], ["CXCR2", "PROPOFOL", "agonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "BENZPIPERYLON", "agonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "CHEMBL411250", "agonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "MEPHENTERMINE", "agonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "REPARIXIN", "allosteric modulator|modulator|antagonist", "GuideToPharmacologyInteractions|ChemblInteractions|TTD", "–"], ["CXCR2", "DANIRIXIN", "antagonist", "GuideToPharmacologyInteractions|ChemblInteractions", "–"], ["CXCR2", "NAVARIXIN", "antagonist", "GuideToPharmacologyInteractions|ChemblInteractions|TTD", "–"], ["CXCR2", "CHEMBL239767", "antagonist", "GuideToPharmacologyInteractions", "–"], ["CXCR2", "NAVARIXIN HYDRATE", "antagonist", "ChemblInteractions", "–"], ["CXCR2", "ELUBRIXIN", "antagonist", "ChemblInteractions|TTD", "–"], ["CXCR2", "Ladarixin", 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