scholarly journals Aberrantly hydroxymethylated differentially expressed genes and the associated protein pathways in osteoarthritis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6425 ◽  
Author(s):  
Yang Fang ◽  
Pingping Wang ◽  
Lin Xia ◽  
Suwen Bai ◽  
Yonggang Shen ◽  
...  

Background The elderly population is at risk of osteoarthritis (OA), a common, multifactorial, degenerative joint disease. Environmental, genetic, and epigenetic (such as DNA hydroxymethylation) factors may be involved in the etiology, development, and pathogenesis of OA. Here, comprehensive bioinformatic analyses were used to identify aberrantly hydroxymethylated differentially expressed genes and pathways in osteoarthritis to determine the underlying molecular mechanisms of osteoarthritis and susceptibility-related genes for osteoarthritis inheritance. Methods Gene expression microarray data, mRNA expression profile data, and a whole genome 5hmC dataset were obtained from the Gene Expression Omnibus repository. Differentially expressed genes with abnormal hydroxymethylation were identified by MATCH function. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the genes differentially expressed in OA were performed using Metascape and the KOBAS online tool, respectively. The protein–protein interaction network was built using STRING and visualized in Cytoscape, and the modular analysis of the network was performed using the Molecular Complex Detection app. Results In total, 104 hyperhydroxymethylated highly expressed genes and 14 hypohydroxymethylated genes with low expression were identified. Gene ontology analyses indicated that the biological functions of hyperhydroxymethylated highly expressed genes included skeletal system development, ossification, and bone development; KEGG pathway analysis showed enrichment in protein digestion and absorption, extracellular matrix–receptor interaction, and focal adhesion. The top 10 hub genes in the protein–protein interaction network were COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL6A1, COL8A1, COL11A1, and COL24A1. All the aforementioned results are consistent with changes observed in OA. Conclusion After comprehensive bioinformatics analysis, we found aberrantly hydroxymethylated differentially expressed genes and pathways in OA. The top 10 hub genes may be useful hydroxymethylation analysis biomarkers to provide more accurate OA diagnoses and target genes for treatment of OA.

2020 ◽  
Author(s):  
Jingdi Yang ◽  
Bo Peng ◽  
Xianzheng Qin ◽  
Tian Zhou

Abstract Background: Although the morbidity and mortality of gastric cancer are declining, gastric cancer is still one of the most common causes of death. Early detection of gastric cancer is of great help to improve the survival rate, but the existing biomarkers are not sensitive to diagnose early gastric cancer. The aim of this study is to identify the novel biomarkers for gastric cancer.Methods: Three gene expression profiles (GSE27342, GSE63089, GSE33335) were downloaded from Gene Expression Omnibus database to select differentially expressed genes. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were performed to explore the biological functions of differentially expressed genes. Cytoscape was utilized to construct protein-protein interaction network and hub genes were analyzed by plugin cytoHubba of Cytoscape. Furthermore, Gene Expression Profiling Interactive Analysis and Kaplan-Meier plotter were used to verify the identified hub genes.Results: 35 overlapping differentially expressed genes were screened from gene expression datasets, which consisted of 11 up-regulated genes and 24 down-regulated genes. Gene Ontology functional enrichment analysis revealed that differentially expressed genes were significantly enriched in digestion, regulation of biological quality, response to hormone and steroid hormone, and homeostatic process. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed differentially expressed genes were enriched in the secretion of gastric acid and collecting duct acid, leukocyte transendothelial migration and ECM-receptor interaction. According to protein-protein interaction network, 10 hub genes were identified by Maximal Clique Centrality method.Conclusion: By using bioinformatics analysis, COL1A1, BGN, THY1, TFF2 and SST were identified as the potential biomarkers for early detection of gastric cancer.


Epigenomics ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1795-1809 ◽  
Author(s):  
Haiyu Cao ◽  
Dong Li ◽  
Huixiu Lu ◽  
Jing Sun ◽  
Haibin Li

Aim: The aim of this study was to find potential differentially expressed long noncoding RNAs (lncRNAs) and mRNAs in systemic lupus erythematosus. Materials & methods: Differentially expressed lncRNAs and mRNAs were obtained in the Gene Expression Omnibus dataset. Functional annotation of differentially expressed mRNAs was performed, followed by protein–protein interaction network analysis. Then, the interaction network of lncRNA-nearby targeted mRNA was built. Results: Several interaction pairs of lncRNA-nearby targeted mRNA including NRIR-RSAD2, RP11-153M7.5-TLR2, RP4-758J18.2-CCNL2, RP11-69E11.4-PABPC4 and RP11-496I9.1-IRF7/ HRAS/ PHRF1 were identified. Measles and MAPK were significantly enriched signaling pathways of differentially expressed mRNAs. Conclusion: Our study identified several differentially expressed lncRNAs and mRNAs. And their interactions may play a crucial role in the process of systemic lupus erythematosus.


2021 ◽  
Author(s):  
Yuxuan HUANG ◽  
Ge CUI

Abstract Aims: To utilize the bioinformatics to analyze the differentially expressed genes (DEGs), interaction proteins, perform gene enrichment analysis, protein-protein interaction network (PPI) and map the hub genes between colorectal cancer(CRC) and colorectal adenocarcinomas(CA).Methods: We analyzed a microarray dataset (GSE32323 and GSE4183) from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in tumor tissues and non-cancerous tissues were identified using the dplyr and Venn diagram packages of the R Studio software. Functional annotation of the DEGs was performed using the Gene Ontology (GO) website. Pathway enrichment (KEGG) used the WebGestalt to analyze the data and R Studio to generate the graph. We constructed a protein–protein interaction (PPI) network of DEGs using STRING and Cytoscape software was used for visualization. Survival analysis of the hub genes and was performed using the online platform GEPIA to determine the prognostic value of the expression of hub genes in cell lines from CRC patients. The expression of molecules with prognostic values was validated on the UALCAN database. The expression of hub genes was examined using the Human Protein Atlas. Results: Applying the GEO2R analysis and R studio, we identified a total of 471 upregulated and 278 downregulated DEGs. By using the online database WebGestalt, we identified the most relevant biological networks involving DEGs with statistically significant differences in expression were mainly associated with biological processes involved in the cell proliferation, cell cycle transition, cell homeostasis and indicated the role of each DEGs in cell cycle regulation pathways. We found 10 hub genes with prognostic values were overexpressed in the CRC and CA samples.Conclusion: we found out ten hub genes and three core genes closely associated with the pathogenesis and prognosis of CRC and CA, which is of great significance for colorectal tumor early detection and prognosis evaluation.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ke-Ying Fang ◽  
Wen-Chao Cao ◽  
Tian-Ao Xie ◽  
Jie Lv ◽  
Jia-Xin Chen ◽  
...  

Abstract Background In the novel coronavirus pandemic, the high infection rate and high mortality have seriously affected people’s health and social order. To better explore the infection mechanism and treatment, the three-dimensional structure of human bronchus has been employed in a better in-depth study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We downloaded a separate microarray from the Integrated Gene Expression System (GEO) on a human bronchial organoids sample to identify differentially expressed genes (DEGS) and analyzed it with R software. After processing with R software, Gene Ontology (GO) and Kyoto PBMCs of Genes and Genomes (KEGG) were analyzed, while a protein–protein interaction (PPI) network was constructed to show the interactions and influence relationships between these differential genes. Finally, the selected highly connected genes, which are called hub genes, were verified in CytoHubba plug-in. Results In this study, a total of 966 differentially expressed genes, including 490 upregulated genes and 476 downregulated genes were used. Analysis of GO and KEGG revealed that these differentially expressed genes were significantly enriched in pathways related to immune response and cytokines. We construct protein-protein interaction network and identify 10 hub genes, including IL6, MMP9, IL1B, CXCL8, ICAM1, FGF2, EGF, CXCL10, CCL2, CCL5, CXCL1, and FN1. Finally, with the help of GSE150728, we verified that CXCl1, CXCL8, CXCL10, CCL5, EGF differently expressed before and after SARS-CoV-2 infection in clinical patients. Conclusions In this study, we used mRNA expression data from GSE150819 to preliminarily confirm the feasibility of hBO as an in vitro model to further study the pathogenesis and potential treatment of COVID-19. Moreover, based on the mRNA differentiated expression of this model, we found that CXCL8, CXCL10, and EGF are hub genes in the process of SARS-COV-2 infection, and we emphasized their key roles in SARS-CoV-2 infection. And we also suggested that further study of these hub genes may be beneficial to treatment, prognostic prediction of COVID-19.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Binfeng Liu ◽  
Ang Li ◽  
Hongbo Wang ◽  
Jialin Wang ◽  
Gongwei Zhai ◽  
...  

The Corneal wound healing results in the formation of opaque corneal scar. In fact, millions of people around the world suffer from corneal scars, leading to loss of vision. This study aimed to identify the key changes of gene expression in the formation of opaque corneal scar and provided potential biomarker candidates for clinical treatment and drug target discovery. We downloaded Gene expression dataset GSE6676 from NCBI-GEO, and analyzed the Differentially Expressed Genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses, and protein-protein interaction (PPI) network. A total of 1377 differentially expressed genes were identified and the result of Functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) identification and protein-protein interaction (PPI) networks were performed. In total, 7 hub genes IL6 (interleukin-6), MMP9 (matrix metallopeptidase 9), CXCL10 (C-X-C motif chemokine ligand 10), MAPK8 (mitogen-activated protein kinase 8), TLR4 (toll-like receptor 4), HGF (hepatocyte growth factor), EDN1 (endothelin 1) were selected. In conclusion, the DEGS, Hub genes and signal pathways identified in this study can help us understand the molecular mechanism of corneal scar formation and provide candidate targets for the diagnosis and treatment of corneal scar.


2020 ◽  
Author(s):  
Zhongxiao Lu ◽  
Jian Wu ◽  
Yi-ming Li ◽  
Wen-xiang Chen ◽  
Qiang-feng Yu ◽  
...  

Abstract AimLiver cancer is a common malignant tumor whose molecular pathogenesis remains unclear. This study attempts to identify key genes related to liver cancer by bioinformatics analysis and analyze their biological functions.MethodsThe gene expression data of the microarray were downloaded from the Gene Expression Omnibus(GEO) database. The differentially expressed genes (DEGs) were then identified by the R software package “limma” and were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using DAVID. The protein-protein interaction (PPI) network was constructed via String, and the results were visualized in Cytoscape. Modules and hub genes were identified using the MCODE plugin, while the expression of hub genes and its effects were analyzed by GEPIA2. Additionally, the co-expression of the hub gene was explored in String, while the GO results were visualized using the R software. Finally, the targets of the hub gene were predicted through an online website. ResultsIn total, 43 differentially expressed genes were obtained. The GO analysis was mainly concentrated in the redox process and nuclear mitosis, while the KEGG pathway analysis was mainly enriched in retinol metabolism and the cell cycle. Moreover, four hub genes were identified in the PPI network, however, the Kaplan-Meier risk curve showed that only ECT2 and FCN3 affected the survival of liver cancer. ECT2 was found to be high expressed in liver cancer, carrying out signal transduction and targeting hsa-miR-27a-3p. FCN3 was observed to be lowly expressed in liver cancer and related to the immune response, targeting hsa-miR132-5p.ConclusionThe obtained findings suggest that two genes are significantly related to the prognosis of liver cancer, and the analysis of their biological function provided novel insight into the pathogenesis of liver cancer. Furthermore, FCN3 may serve as a promising biomarker for patients with liver cancer.


2021 ◽  
Author(s):  
Zhu Lili ◽  
Zhu YuKun ◽  
Zhuangzhuang Tian ◽  
Yongsheng Li ◽  
Liyu Cao

Abstract Background Classic Hodgkin lymphoma (CHL) is the most common HL in the modern society. Although the treatment of cHL has made great progress, its molecular mechanisms have yet to be deciphered. Objectives The purpose of this study is to find out the crucial potential genes and pathways associated with cHL. Methods We downloaded the cHL microarray dataset (GSE12453) from Gene Expression Omnibus (GEO) database and to identify the differentially expressed genes (DEGs) between cHL samples and normal samples through the limma package in R. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were carried out. Finally, we constructed the protein-protein interaction network to screen out the hub genes using Search Tool for the Retrieval of Interacting Genes (STRING) database. Results We screened out 788 DEGs in the cHL dataset, such as BATF3, IER3, RAB13 and FCRL2. GO functional enrichment analysis indicated that the DEGs were related with regulation of lymphocyte activation, secretory granule lumen and chemokine activity. KEGG pathway analysis showed that the genes enriched in Prion disease, Complement and coagulation cascades and Parkinson disease Coronavirus disease-COVID-19 pathway. Protein-protein interaction network construction identified 10 hub genes (IL6, ITGAM, CD86, FN1, MMP9, CXCL10, CCL5, CD19, IFNG, SELL, UBB) in the network. Conclusions In the present investigation, we identified several pathways and hub genes related to the occurrence and development of cHL, which may provide an important basis for further research and novel therapeutic targets and prognostic indicators for cHL.


2021 ◽  
Vol 20 ◽  
pp. 153303382199036
Author(s):  
Kai Cui ◽  
Jin-hui Chen ◽  
Yang-fan Zou ◽  
Shu-yuan Zhang ◽  
Bing Wu ◽  
...  

Background: Glioblastoma (GBM) is the most common clinical intracranial malignancy worldwide, and the most common supratentorial tumor in adults. GBM mainly causes damage to the brain tissue, which can be fatal. This research explored potential gene targets for the diagnosis and treatment of GBM using bioinformatic technology. Methods: Public data from patients with GBM and controls were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified by Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus 2R (GEO2R). Construction of the protein–protein interaction network and the identification of a significant module were performed. Subsequently, hub genes were identified, and their expression was examined and compared by real-time quantitative (RT-q)PCR between patients with GBM and controls. Results: GSE122498 (GPL570 platform), GSE104291 (GPL570 platform), GSE78703_DMSO (GPL15207 platform), and GSE78703_LXR (GPL15207 platform) datasets were obtained from the GEO. A total of 130 DEGs and 10 hub genes were identified by GEPIA and GEO2R between patients with GBM and controls. Of these, strong connections were identified in correlation analysis between CCNB1, CDC6, KIF23, and KIF20A. RT-qPCR showed that all 4 of these genes were expressed at significantly higher levels in patients with GBM compared with controls. Conclusions: The hub genes CCNB1, CDC6, KIF23, and KIF20A are potential biomarkers for the diagnosis and treatment of GBM.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 896-897
Author(s):  
W. Liu ◽  
X. Zhang

Background:Myositis, including dermatomyositis and polymyositis, is autoimmune disorders that is characterized by muscle degeneration in the proximal extremities, with the complications of weakness of muscles, interstitial lung disease and vascular lesions, even leading to death in an acute progressive process[1,2]. However, the molecular mechanisms of myositis are rarely understood.Objectives:Identify the candidate genes in myositis.Methods:Microarray datasets GSE128470, GSE48280 and GSE39454 were extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and function enrichment analyses were conducted. The protein-protein interaction network and the analyses of hub genes were performed with STRING and Cytoscape.Results:There were 98 DEGs, of which the function and pathways enrichment analyses showed defense response, immune response, response to virus, inflammatory response, response to wounding, cell adhesion, cell proliferation, cell death and macromolecule metabolic process. 20 hub genes were identified, of which 7 including IRF9 TRIM22 MX2 IFITM1 IFI6 IFI44 IFI44L had not been reported in the literature, related to the response to virus, immune response, transcription from RNA polymerase II promoter, cell apoptosis, cell death. The verification analysis about the 7 genes in GSE128314 showed significant differences in myositis.Conclusion:In conclusion, DEGs and hub genes identified in our study showed the potential molecular mechanisms in myositis, providing the helpful targets for diagnosis and clinical strategy of myositis.References:[1] Wu H, Geng D, Xu J. An approach to the development of interstitial lung disease in dermatomyositis: a study of 230 cases in China[J]. Journal of International Medical Research. 2013;41(2):493–501.[2] Fathi M, Dastmalchi M, Rasmussen E, Lundberg IE, Tornling G. Interstitial lung disease, a common manifestation of newly diagnosed polymyositis and dermatomyositis[J]. Annals of the Rheumatic Diseases. 2004;63(3):297–301.Figure 1.The protein-protein interaction network of 20 hub genesFigure 2.7 genes in GSE128314 showed significant differences in myositisAcknowledgments:The authors acknowledge the efforts of the Gene Expression Omnibus (GEO) database. The interpretation and reporting of these data are the sole responsibility of the authors.Disclosure of Interests:None declared


2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Jing Han ◽  
Xue Zhang ◽  
Yang Yang ◽  
Li Feng ◽  
Gui-Ying Wang ◽  
...  

Purpose. Colon adenocarcinoma (COAD) is the third most common malignancy globally and is further categorized as left colon adenocarcinoma (LCOAD) or right colon adenocarcinoma (RCOAD) depending on the location of the primary tumor. The therapeutic outcome and long-term prognosis for patients with COAD are less than satisfactory, and this may be associated with tumor location. Therefore, it is important to investigate the genetic differences in COAD at different sites. Patients and Methods. Public data associated with COAD were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using R software (version 3.5.3), and functional annotation of DEGs was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction network was constructed, hub genes were identified and analyzed, and data mining using Gene Expression Profiling Interactive Analysis (GEPIA) was conducted. Results. A total of 286 DEGs were identified between LCOAD and RCOAD. Additionally, 10 hub genes associated with COAD at different locations were screened, namely, CDKN2A, IGF1R, MDM2, SMAD3, SLC2A1, GRM5, PLCB4, FGFR1, UBE2V2, and TNFRSF10B. The expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) and solute carrier family 2 member 1 (SLC2A1) was significantly associated with pathological stage P<0.05. COAD patients with high expression levels of CDKN2A exhibited poorer overall survival (OS) times than those with low expression levels P<0.05. Conclusion. CDKN2A expression was significantly different between LCOAD and RCOAD and was closely related to the prognosis of COAD. It is of great value for further understanding of the pathogenesis of LCOAD and RCOAD.


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