Screening and identification of differentially expressed genes between diabetic nephropathy glomerular and normal glomerular via bioinformatics technology

Author(s):  
Junjie Du ◽  
Jihong Yang ◽  
Lingbing Meng

Background: Diabetes is a chronic metabolic disease characterized by disorders of glucose and lipid metabolism. Its most serious microvascular complication is diabetic nephropathy (DN), which is characterized by varying degrees of proteinuria and progressive glomerulosclerosis, eventually progressing to end-stage renal failure. Objective: The aim of this research is to identify hub genes which might serve as genetic markers to enhance the diagnosis, treatment, and prognosis of DN. Method: The procedures of the study include access to public data, identification of differentially expressed genes (DEGs) by GEO2R, and functional annotation of DEGs using enrichment analysis. Subsequently, construction of the protein-protein interaction (PPI) network and identification of significant modules were performed. Finally, the hub genes were identified and analyzed, including clustering analysis, Pearson's correlation coefficient analysis, and multivariable linear regression analysis. Results: Between the GSE30122 and GSE1009 datasets a total of 142 DEGs were identified, which were mainly enriched in cell migration, platelet activation, glomerulus development, glomerular basement membrane development, focal adhesion, regulation of actin cytoskeleton, and the PI3K-AKT signaling pathway. The PPI network was composed of 205 edges and 142 nodes. A total of 10 hub genes (VEGFA, NPHS1, WT1, PODXL, TJP1, FYN, SULF1, ITGA3, COL4A3, and FGF1) were identified from the PPI network. Conclusion: The DEGs between DN and control glomeruli samples may be involved in the occurrence and development of DN. We speculated that hub genes may be important inhibitory genes in the pathogenesis of diabetic nephropathy, so they are expected to become the new gene targets for the treatment of DN.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Feng Yao ◽  
Zhao Feng Zhu ◽  
Jun Wen ◽  
Fu Yong Zhang ◽  
Zheng Zhang ◽  
...  

Abstract Background Osteosarcoma was the most common primary bone malignancy in children and adolescents. It was imperative to identify effective prognostic biomarkers for this cancer. This study was aimed to identify potential crucial genes of osteosarcoma by integrated bioinformatics analysis. Methods Identification of differentially expressed genes from public data gene expression profiles (GSE42352), functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction and module analysis, Cox regression and survival analysis was conducted. Results Totally 17 co-differential genes were found to be differentially expressed. These genes were enriched in biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway of inflammatory immune response. PPI network was constructed with 63 differentially expressed genes that co-existed between the test set and the validation set. The area under the receiver operating characteristic curve (AUC value) was 0.855, which indicated that the expression of PODN had a good diagnostic value for osteosarcoma. Furthermore, Cox regression and survival analysis revealed 5 genes were statistically significant. Conclusions PODN was regarded as a potential biomarker for the diagnosis and prognosis of osteosarcoma, ACTA2, COL6A1, FAP, OLFML2B and COL6A3, can be used as potential prognostic indicators for osteosarcoma.


2020 ◽  
Author(s):  
Rongrong Xiao ◽  
Ping Wang ◽  
Tian Xia ◽  
Chun-Yi Li ◽  
Ting Jiang ◽  
...  

Abstract Background Tumor microenvironment plays important roles in the development of cancer. The aim of our study was to examine the expression of genes in colorectal cancer and also to evaluate the association value between expression level of these genes and clinical features. Methods We combined The Cancer Genome Atlas (TCGA) datasets to identify differentially expressed genes in colon cancer. Using these differentially expressed genes, we constructed protein-protein interaction network and conducted functional enrichment analysis. Genes with degree beyond 10 in the PPI network were regarded as hub genes. Then, we verified of the expression of molecules in Oncomine datasets and conducted Kaplan-Meier curve and log-rank test and functional enrichment analysis on these hub genes. Finally, we analyzed the relationship clinicopathological features analysis with the key gene. Results There were 719 differentially expressed genes identified to be associated with colon cancer microenvironment. We screened out 10 hub genes by construction of PPI network. The functions of these hub genes were enriched in cytokine-cytokine receptor interaction, alcoholism and systemic lupus erythematosus, which provided further insight into the roles of these genes in the tumor microenvironment. GNG4, with the highest degrees in the PPI network, were highly exprepressed in metastasis(P = 9.5-05) ,N1(P = 0.0025) and N2(,0.037).It was a relationship with stage. It was significantly different between with stage I and IV, II and III, II and IV,III and IV (P = 0.0015,0.029,3.9-05,0.00074,0.01,respectively) Conclusions We identified GNG4 can be regarded as a prognostic biomarker in colon cancer.


Author(s):  
Xitong Yang ◽  
Pengyu Wang ◽  
Shanquan Yan ◽  
Guangming Wang

AbstractStroke is a sudden cerebrovascular circulatory disorder with high morbidity, disability, mortality, and recurrence rate, but its pathogenesis and key genes are still unclear. In this study, bioinformatics was used to deeply analyze the pathogenesis of stroke and related key genes, so as to study the potential pathogenesis of stroke and provide guidance for clinical treatment. Gene Expression profiles of GSE58294 and GSE16561 were obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IS and normal control group. The different expression genes (DEGs) between IS and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA), the function and pathway enrichment analysis of DEGS were performed. Then, a protein–protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. A total of 85 DEGs were screened out in this study, including 65 upward genes and 20 downward genes. In addition, 3 KEGG pathways, cytokine − cytokine receptor interaction, hematopoietic cell lineage, B cell receptor signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the PPI network and CytoHubba, 10 hub genes including CEACAM8, CD19, MMP9, ARG1, CKAP4, CCR7, MGAM, CD79A, CD79B, and CLEC4D were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including hsa-mir-146a-5p, hsa-mir-7-5p, hsa-mir-335-5p, and hsa-mir-27a- 3p, were predicted as possibly the key miRNAs. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of ischemic stroke, and provide a new strategy for clinical therapy.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Baojie Wu ◽  
Shuyi Xi

Abstract Background This study aimed to explore and identify key genes and signaling pathways that contribute to the progression of cervical cancer to improve prognosis. Methods Three gene expression profiles (GSE63514, GSE64217 and GSE138080) were screened and downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) were screened using the GEO2R and Venn diagram tools. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Gene set enrichment analysis (GSEA) was performed to analyze the three gene expression profiles. Moreover, a protein–protein interaction (PPI) network of the DEGs was constructed, and functional enrichment analysis was performed. On this basis, hub genes from critical PPI subnetworks were explored with Cytoscape software. The expression of these genes in tumors was verified, and survival analysis of potential prognostic genes from critical subnetworks was conducted. Functional annotation, multiple gene comparison and dimensionality reduction in candidate genes indicated the clinical significance of potential targets. Results A total of 476 DEGs were screened: 253 upregulated genes and 223 downregulated genes. DEGs were enriched in 22 biological processes, 16 cellular components and 9 molecular functions in precancerous lesions and cervical cancer. DEGs were mainly enriched in 10 KEGG pathways. Through intersection analysis and data mining, 3 key KEGG pathways and related core genes were revealed by GSEA. Moreover, a PPI network of 476 DEGs was constructed, hub genes from 12 critical subnetworks were explored, and a total of 14 potential molecular targets were obtained. Conclusions These findings promote the understanding of the molecular mechanism of and clinically related molecular targets for cervical cancer.


2021 ◽  
Author(s):  
Li Guoquan ◽  
Du Junwei ◽  
He Qi ◽  
Fu Xinghao ◽  
Ji Feihong ◽  
...  

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.


2021 ◽  
Author(s):  
Ke-Ying Fang ◽  
Gui-Ning Liang ◽  
Zhuo-Qing Zhuang ◽  
Yong-Xin Fang ◽  
Yu-Qian Dong ◽  
...  

Abstract Background: With the worldwide spread of COVID-19, people’s health and social order have been exposed to enormous risks. After encountering patients who test positive again after discharge, our study analyzed the pathogenesis to further assess the risk and possibility of virus reactivation.Methods: A separate microarray was acquired from the Integrated Gene Expression System (GEO), and its samples were divided into two groups: a “convalescent-RTP” group consisting of recovery and “retesting-positive” (RTP) patients (group CR) and a “health-RTP” group consisting of healthy control and RTP patients (group HR). The enrichment analysis was performed with R software, obtaining the gene ontology (GO) and Kyoto pluripotent stem cells (KEGG) of the genes and genomes. Subsequently, the protein–protein interaction (PPI) networks of each group were established and the hub genes were discovered using the cytoHubba plug-in.Results: In this study, 20 differentially expressed genes were identified, and 6622 genes were identified in the group CR, consisting of 5003 up-regulated and 1619 down-regulated genes. Meanwhile, 7335 genes were screened in the group HR, including 4323 up-regulated and 3012 down-regulated ones. The GO and KEGG analysis of the two groups revealed significant enrichment of these differentially expressed genes in pathways associated with immune response and apoptosis. In the PPI network constructed, 10 hub genes in group CR were identified, including TP53BP1, SNRPD1, SNRPD2, SF3B1, SNRNP200, MRPS16, MRPS9, CALM1, PPP2R1A, YWHAZ. Similarly, TP53BP1, RPS15, EFTUD2, MRPL16, MRPL17, MRPS14, RPL35A, MRPL32, MRPS6, POLR2G were selected as hub genes.Conclusions: Using the messenger ribonucleic acid (mRNA) expression data from GSE166253, we explore the pathogenesis of retesting positive in COVID-19 from the immune mechanism and molecular level. We found TP53BP1, SNRPD1 and SNRPD2 as hub genes in RTP patients. Hence, their regulatory pathway is vital to the management and prognostic prediction of RTP patients, rendering the further study of these hub genes necessary.


2020 ◽  
Author(s):  
Chao Xu ◽  
HuiFang Li ◽  
YunPeng Zhang ◽  
TianYu Liu ◽  
Yi Feng

Abstract Background: Neuropathic pain can cause significant physical and economic burden to people, and there are no effective long-term treatment methods for this condition. We conducted a bioinformatics analysis of microarray data to identify related mechanisms to determine strategies for more effective treatments of neuropathic pain.Methods: GSE24982 and GSE63442 microarray datasets were extracted from the Gene Expression Omnibus (GEO) database to analyze transcriptome differences of neuropathic pain in the dorsal root ganglions caused by spinal nerve ligation. We filtered the differentially expressed genes (DEGs) in the two datasets and Webgestalt was applied to conduct GeneOntology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the shared DEGs. String Database and Cytoscape software were used to construct the Protein-Protein Interaction (PPI) network to determine the hub genes, which were subsequently verified in the GSE30691 dataset. Finally, miRDB and miRWalk Databases were used to predict potential miRNA of the selected DEGs.Results: A total of 182 overlapped DEGs were found between GSE24982 and GSE63442 datasets. The GO functional analysis and KEGG enrichment analysis showed that the selected DEGs were mainly enriched in infection, transmembrane transport of ion channels, and synaptic transmission. Combining the results of PPI analysis and the verification of the GSE30691 dataset, we identified seven hub genes related to neuropathic pain (Atf3, Aif1, Ctss, Gfap, Scg2, Jun, and Vgf). Predicted miRNA targeting each selected hub genes were identified.Conclusion: Seven hub genes related to the pathogenesis of neuropathic pain and potential targeting miRNA were identified, expanding understanding of the mechanism of neuropathic pain and facilitating treatment development.


2019 ◽  
Vol 48 (5) ◽  
pp. 030006051988726
Author(s):  
Yuting Zhang ◽  
Bo Shen ◽  
Liya Zhuge ◽  
Yong Xie

Objective We aimed to identify differentially expressed genes (DEG) in patients with inflammatory bowel disease (IBD). Methods RNA-seq data were obtained from the Array Express database. DEG were identified using the edgeR package. A co-expression network was constructed and key modules with the highest correlation with IBD inflammatory sites were identified for analysis. The Cytoscape MCODE plugin was used to identify key sub-modules of the protein–protein interaction (PPI) network. The genes in the sub-modules were considered hub genes, and functional enrichment analysis was performed. Furthermore, we constructed a drug–gene interaction network. Finally, we visualized the hub gene expression pattern between the colon and ileum of IBD using the ggpubr package and analyzed it using the Wilcoxon test. Results DEG were identified between the colon and ileum of IBD patients. Based on the co-expression network, the green module had the highest correlation with IBD inflammatory sites. In total, 379 DEG in the green module were identified for the PPI network. Nineteen hub genes were differentially expressed between the colon and ileum. The drug–gene network identified these hub genes as potential drug targets. Conclusion Nineteen DEG were identified between the colon and ileum of IBD patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jiahuan Luo ◽  
Li Zhu ◽  
Ning Zhou ◽  
Yuanyuan Zhang ◽  
Lirong Zhang ◽  
...  

Background: Many studies on circular RNAs (circRNAs) have recently been published. However, the function of circRNAs in recurrent implantation failure (RIF) is unknown and remains to be explored. This study aims to determine the regulatory mechanisms of circRNAs in RIF.Methods: Microarray data of RIF circRNA (GSE147442), microRNA (miRNA; GSE71332), and messenger RNA (mRNA; GSE103465) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed circRNA, miRNA, and mRNA. The circRNA–miRNA–mRNA network was constructed by Cytoscape 3.8.0 software, then the protein–protein interaction (PPI) network was constructed by STRING database, and the hub genes were identified by cytoHubba plug-in. The circRNA–miRNA–hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in RIF. Finally, the Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the hub genes were performed by clusterProfiler package of Rstudio software, and Reactome Functional Interaction (FI) plug-in was used for reactome analysis to comprehensively analyze the mechanism of hub genes in RIF.Results: A total of eight upregulated differentially expressed circRNAs (DECs), five downregulated DECs, 56 downregulated differentially expressed miRNAs (DEmiRs), 104 upregulated DEmiRs, 429 upregulated differentially expressed genes (DEGs), and 1,067 downregulated DEGs were identified regarding RIF. The miRNA response elements of 13 DECs were then predicted. Seven overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 56 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of seven miRNAs with 1,496 DEGs. The circRNA–miRNA–mRNA network and PPI network were constructed through six circRNAs, seven miRNAs, and 56 mRNAs; and four hub genes (YWHAZ, JAK2, MYH9, and RAP2C) were identified. The circRNA–miRNA–hub gene regulatory subnetwork with nine regulatory axes was formed in RIF. Functional enrichment analysis and reactome analysis showed that these four hub genes were closely related to the biological functions and pathways of RIF.Conclusion: The results of this study provide further understanding of the potential pathogenesis from the perspective of circRNA-related competitive endogenous RNA network in RIF.


2021 ◽  
Author(s):  
Churen Zhang ◽  
Ruoran Sun

Abstract Background. Among the diseases of oral mucosa, oral lichen planus (OLP) is characterized by chronic autoimmune/autoinflammation. However, the etiology and pathogenesis of OLP were still limited. The aim of this research was to identify the differentially expressed genes and their potentially interacted miRNAs in OLP to provide a possible explanation of the pathogenesis of OLP and therapeutic biomarkers.Methods. The OLP microarray dataset (GSE52130) was download from the Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes between the OLP samples and normal oral mucosa. Functional enrichment analysis of DEGs, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, were conducted. Protein–protein interaction (PPI) network analysis was performed in the STRING database. CytoHubba in the Cytoscape software was applied to determining the top 10 hub genes, whose relative miRNA was identified through RNA Interactome Database.Results. Overall, 627 DEGs was identified in OLP samples, including 351 highly expressed genes and 276 lowly expressed genes. GO analysis indicated that the epidermal differentiation was mostly enriched. For the KEGG pathway, the DEGs in OLP samples were mostly involved in Staphylococcus aureus infection, Estrogen signaling pathway, Serotonergic synapse and Histidine metabolism. Top 10 hub genes including LOR, LCE3D, LCE3E, LCE1B, LCE2B, SPRR2E, SPRR2G, LCE2A, RPTN and CDSN were identified from the PPI network. The miRNA (hsa-miR-98-5p) was regarded as the mostly possible miRNA involved in OLP.


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