scholarly journals Identification of differentially expressed genes between the colon and ileum of patients with inflammatory bowel disease by gene co-expression analysis

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 ◽  
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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Min Li ◽  
Wenye Zhu ◽  
Chu Wang ◽  
Yuanyuan Zheng ◽  
Shibo Sun ◽  
...  

Abstract Background Asthma is a heterogeneous disease that can be divided into four inflammatory phenotypes: eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma (MGA), and paucigranulocytic asthma (PGA). While research has mainly focused on EA and NA, the understanding of PGA is limited. In this study, we aimed to identify underlying mechanisms and hub genes of PGA. Methods Based on the dataset from Gene Expression Omnibus(GEO), weighted gene coexpression network analysis (WGCNA), differentially expressed genes (DEGs) analysis and protein–protein interaction (PPI) network analysis were conducted to construct a gene network and to identify key gene modules and hub genes. Functional enrichment analyses were performed to investigate the biological process, pathways and immune status of PGA. The hub genes were validated in a separate dataset. Results Compared to non-PGA, PGA had a different gene expression pattern, in which 449 genes were differentially expressed. One gene module significantly associated with PGA was identified. Intersection between the differentially expressed genes (DEGs) and the genes from the module that were most relevant to PGA were mainly enriched in inflammation and immune response regulation. The single sample Gene Set Enrichment Analysis (ssGSEA) suggested a decreased immune infiltration and function in PGA. Finally six hub genes of PGA were identified, including ADCY2, CXCL1, FPRL1, GPR109B, GPR109A and ADCY3, which were validated in a separate dataset of GSE137268. Conclusions Our study characterized distinct gene expression patterns, biological processes and immune status of PGA and identified hub genes, which may improve the understanding of underlying mechanism and provide potential therapeutic targets for PGA.


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.


2021 ◽  
Author(s):  
Feifei Liu ◽  
Yu Wang ◽  
Wenxue Li ◽  
Diancheng Li ◽  
Yuwei Xin ◽  
...  

Abstract Background: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system; the progression and prognosis of which are affected by a complicated network of genes and pathways. The aim of this study was to identify potential hub genes associated with the progression and prognosis of colorectal cancer (CRC).Methods: We obtained gene expression profiles from GEO database to search differentially expressed genes (DEGs) between CRC tissues and normal tissue. Subsequently, we conducted a functional enrichment analysis, generated a protein–protein interaction (PPI) network to identify the hub genes, and analyzed the expression validation of the hub genes. Kaplan–Meier plotter survival analysis tool was performed to evaluate the prognostic value of hub genes expression in CRC patients.Results: A total of 370 samples, involving CRC and normal tissues were enrolled in this article. 283 differentially expressed genes (DEGs), including 62 upregulated genes and 221 downregulated genes between CRC and normal tissues were selected. We finally filtered out 6 hub genes, including INSL5, MTIM, GCG, SPP1, HSD11B2, and MAOB. In the database of TCGA-COAD, the mRNA expression of INSL5, MT1M, HSD11B2, MAOB in tumor is lower than that in normal; the mRNA expression of SPP1 in tumor is higher than that in normal. In the HPA database, the expression of INSL5, GCG, HSD11B2, MAOB in tumor is lower than that in normal tissues; the expression of SPP1 in the tumor is higher than that in normal tissues. Survival analysis revealed that INSL5, GCG, SPP1 and MT1M may serve as prognostic biomarkers in CRC. Conclusions: We screened out six hub genes to predict the occurrence and prognosis of patients with CRC using bioinformatics methods, which may provide new targets and ideas for diagnosis, prognosis and individualized treatment for CRC.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
LongGui Ning ◽  
Guodong Shan ◽  
Zeyu Sun ◽  
Fenming Zhang ◽  
Chengfu Xu ◽  
...  

Inflammatory bowel disease (IBD) has become a major health challenge worldwide. However, the precise etiological and pathophysiological factors involved in IBD remain unclear. Proteomics can be used for large-scale protein identification analysis. In the current study, using tandem mass tag- (TMT-) based shotgun proteomics, proteomic differences between intestinal tissue from health controls, patients with Crohn’s disease (CD), and patients with ulcerative colitis (UC) were compared. Proteins with fold change >2 or <0.5 and P value < 0.05 between groups were considered differentially expressed. ProteinAtlas was used to analyze the tissue specificity of differentially expressed proteins (DEPs). Reactome pathway analysis was applied to cluster functional pathways. A total of 4786 proteins were identified, with 59 proteins showing higher levels and 43 showing lower levels in patients with IBD than in controls. Seventeen proteins, including angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme 1 (ACE), showed higher levels in CD than in UC. Several novel proteins such as CD38, chitinase 3-like 1 (CHI3L1), olfactomedin 4 (OLFM4), and intelectin 1 were screened out between patients with IBD and controls. When proteins with fold change >1.2 or <0.84 and P value < 0.05 between groups were considered differentially expressed, the expression of 10 proteins, including CD38, involved in the nicotinamide adenine dinucleotide (NAD) metabolism and signaling pathway showed significant changes in IBD. Using the NCBI GEO database, we confirmed increased CD38 mRNA expression in patients with UC and in mouse colitis models. Protein CD38 expression was higher in CD and UC than in normal controls. CD38 expression was higher in inflamed tissues than in noninflamed tissues, and CD38 was located in F4/80-positive cells. Our study may provide novel insights into the molecular pathogenesis of IBD. Further studies are required on the role of NAD metabolism and CD38 in intestinal inflammation.


2020 ◽  
Vol 21 (2) ◽  
pp. 147032032091963
Author(s):  
Xiaoxue Chen ◽  
Mindan Sun

Purpose: This study aims to identify immunoglobulin-A-nephropathy-related genes based on microarray data and to investigate novel potential gene targets for immunoglobulin-A-nephropathy treatment. Methods: Immunoglobulin-A-nephropathy chip data was obtained from the Gene Expression Omnibus database, which included 10 immunoglobulin-A-nephropathy and 22 normal samples. We used the limma package of R software to screen differentially expressed genes in immunoglobulin-A-nephropathy and normal glomerular compartment tissues. Functional enrichment (including cellular components, molecular functions, biological processes) and signal pathways were performed for the differentially expressed genes. The online analysis database (STRING) was used to construct the protein-protein interaction networks of differentially expressed genes, and Cytoscape software was used to identify the hub genes of the signal pathway. In addition, we used the Connectivity Map database to predict possible drugs for the treatment of immunoglobulin-A-nephropathy. Results: A total of 348 differentially expressed genes were screened including 107 up-regulated and 241 down-regulated genes. Functional analysis showed that up-regulated differentially expressed genes were mainly concentrated on leukocyte migration, and the down-regulated differentially expressed genes were significantly enriched in alpha-amino acid metabolic process. A total of six hub genes were obtained: JUN, C3AR1, FN1, AGT, FOS, and SUCNR1. The small-molecule drugs thapsigargin, ciclopirox and ikarugamycin were predicted therapeutic targets against immunoglobulin-A-nephropathy. Conclusion: Differentially expressed genes and hub genes can contribute to understanding the molecular mechanism of immunoglobulin-A-nephropathy and providing potential therapeutic targets and drugs for the diagnosis and treatment of immunoglobulin-A-nephropathy.


Reproduction ◽  
2017 ◽  
Vol 153 (5) ◽  
pp. 645-653 ◽  
Author(s):  
Miao Zhao ◽  
Wen-Qian Zhang ◽  
Ji-Long Liu

Although regional differences in mouse decidualization have been recognized for decades, the molecular mechanisms remain understudied. In the present study, by using RNA-seq, we compared transcriptomic differences between the anti-mesometrial (AM) region and the mesometrial (M) region of mouse uterus on day 8 of pregnancy. A total of 1423 differentially expressed genes were identified, of which 811 genes were upregulated and 612 genes were downregulated in the AM region compared to those in the M region. Gene ontology analysis showed that upregulated genes were generally involved in cell metabolism and differentiation, whereas downregulated genes were associated with lymphocyte themes and immune response. Through network analysis, we identified a total of 6 hub genes. These hub genes are likely more important than other genes due to their key positions in the network. We also examined the promoter regions of differentially expressed genes for the enrichment of transcription factor-binding sites. In the end, we demonstrated that a similar regional gene expression pattern can be observed in the artificial decidualization model. Our study contributes to an increase in the knowledge on the molecular mechanisms underlying regional decidualization in mice.


2021 ◽  
Author(s):  
Pejman Morovat ◽  
Saman Morovat ◽  
Arash M. Ashrafi ◽  
Shahram Teimourian

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, which has a high mortality rate and poor treatment outcomes with yet unknown molecular basis. It seems that gene expression plays a pivotal role in the pathogenesis of the disease. Circular RNAs (circRNAs) can interact with microRNAs (miRNAs) to regulate gene expression in various malignancies by acting as competitive endogenous RNAs (ceRNAs). However, the potential pathogenesis roles of the ceRNA network among circRNA/miRNA/mRNA in HCC are unclear. In this study, first, the HCC circRNA expression data were obtained from three Gene Expression Omnibus microarray datasets (GSE164803, GSE94508, GSE97332), and the differentially expressed circRNAs (DECs) were identified using R limma package. Also, the liver hepatocellular carcinoma (LIHC) miRNA and mRNA sequence data were retrieved from TCGA, and differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) were determined using the R DESeq2 package. Second, CSCD website was used to uncover the binding sites of miRNAs on DECs. The DECs' potential target miRNAs were revealed by conducting an intersection between predicted miRNAs from CSCD and downregulated DEMIs. Third, some related genes were uncovered by intersecting targeted genes predicted by miRWalk and targetscan online tools with upregulated DEGs. The ceRNA network was then built using the Cytoscape software. The functional enrichment and the overall survival time of these potential targeted genes were analyzed, and a PPI network was constructed in the STRING database. Network visualization was performed by Cytoscape, and ten hub genes were detected using the CytoHubba plugin tool. Four DECs (hsa_circ_0000520, hsa_circ_0008616, hsa_circ_0070934, hsa_circ_0004315) were obtained and six miRNAs (hsa-miR-542-5p, hsa-miR-326, hsa-miR-511-5p, hsa-miR-195-5p, hsa-miR-214-3p, and hsa-miR-424-5p) which are regulated by the above DECs were identified. Then 543 overlapped genes regulated by six miRNAs mentioned above were predicted. Functional enrichment analysis showed that these genes are mostly associated with cancer regulation functions. Ten hub genes (TTK،AURKB, KIF20A، KIF23، CEP55، CDC6، DTL، NCAPG، CENPF، PLK4) have been screened from the PPI network of the 204 survival-related genes. KIF20A, NCAPG, TTK, PLK4, and CDC6 were selected for the highest significant p-values. In the end, a circRNA-miRNA-mRNA regulatory axis was established for five final selected hub genes. This study implies the potential pathogenesis of the obtained network and proposes that the two DECs (has_circ_0070934 and has_circ_0004315) may be important prognostic factor for HCC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guofeng Zhou ◽  
Shaoyan Sun ◽  
Qiuyue Yuan ◽  
Run Zhang ◽  
Ping Jiang ◽  
...  

Heart failure with preserved ejection fraction (HFpEF) is a complex disease characterized by dysfunctions in the heart, adipose tissue, and cerebral arteries. The elucidation of the interactions between these three tissues in HFpEF will improve our understanding of the mechanism of HFpEF. In this study, we propose a multilevel comparative framework based on differentially expressed genes (DEGs) and differentially correlated gene pairs (DCGs) to investigate the shared and unique pathological features among the three tissues in HFpEF. At the network level, functional enrichment analysis revealed that the networks of the heart, adipose tissue, and cerebral arteries were enriched in the cell cycle and immune response. The networks of the heart and adipose tissues were enriched in hemostasis, G-protein coupled receptor (GPCR) ligand, and cancer-related pathway. The heart-specific networks were enriched in the inflammatory response and cardiac hypertrophy, while the adipose-tissue-specific networks were enriched in the response to peptides and regulation of cell adhesion. The cerebral-artery-specific networks were enriched in gene expression (transcription). At the module and gene levels, 5 housekeeping DEGs, 2 housekeeping DCGs, 6 modules of merged protein–protein interaction network, 5 tissue-specific hub genes, and 20 shared hub genes were identified through comparative analysis of tissue pairs. Furthermore, the therapeutic drugs for HFpEF-targeting these genes were examined using molecular docking. The combination of multitissue and multilevel comparative frameworks is a potential strategy for the discovery of effective therapy and personalized medicine for HFpEF.


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.


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