scholarly journals Identification of Key Pathways and Genes in SARS-CoV-2 Infecting Human Intestines by Bioinformatics Analysis

Author(s):  
Ji-Chun Chen ◽  
Tian-Ao Xie ◽  
Zhen-Zong Lin ◽  
Yi-Qing Li ◽  
Yu-Fei Xie ◽  
...  

AbstractCOVID-19 is a serious infectious disease that has recently swept the world, and research on its causative virus, SARS-CoV-2, remains insufficient. Therefore, this study uses bioinformatics analysis techniques to explore the human digestive tract diseases that may be caused by SARS-CoV-2 infection. The gene expression profile data set, numbered GSE149312, is from the Gene Expression Omnibus (GEO) database and is divided into a 24-h group and a 60-h group. R software is used to analyze and screen out differentially expressed genes (DEGs) and then gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses are performed. In KEGG, the pathway of non-alcoholic fatty liver disease exists in both the 24-h group and 60-h group. STRING is used to establish a protein–protein interaction (PPI) network, and Cytoscape is then used to visualize the PPI and define the top 12 genes of the node as the hub genes. Through verification, nine statistically significant hub genes are identified: AKT1, TIMP1, NOTCH, CCNA2, RRM2, TTK, BUB1B, KIF20A, and PLK1. In conclusion, the results of this study can provide a certain direction and basis for follow-up studies of SARS-CoV-2 infection of the human digestive tract and provide new insights for the prevention and treatment of diseases caused by SARS-CoV-2.

2020 ◽  
Vol 23 (5) ◽  
pp. 411-418
Author(s):  
Zhongqiu Li ◽  
Peng Zhang ◽  
Feifei Feng ◽  
Qiao Zhang

Background: Osteosarcoma is one of the most serious primary malignant bone tumors that threaten the lives of children and adolescents. However, the mechanism underlying and how to prevent or treat the disease have not been well understood. Aims & Objective: This aim of the present study was to identify the key genes and explore novel insights into the molecular mechanism of miR-542-3p over-expressed Osteosarcoma. Materials & Methods: Gene expression profile data GDS5367 was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened using GEO2R, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID database. And protein-protein interaction (PPI) network was constructed by the STRING database. In addition, the most highly connected module was screened by plugin MCODE and hub genes by plugin CytoHubba. Furthermore, UALCAN and The Cancer Genome Atlas were performed for survival analysis. Result: In total, 1421 DEGs were identified, including 598 genes were up-regulated and 823 genes were down-regulated. GO analysis showed that DEGs were classified into three groups and DEGs mainly enriched in Steroid biosynthesis, Ubiquitin mediated proteolysis and p53 signaling pathway. Six hub genes (UBA52, RNF114, UBE2H, TRIP12, HNRNPC, and PTBP1) may be key genes with the progression of osteosarcoma. Conclusion: The results could better understand the mechanism of osteosarcoma, which may facilitate a novel insight into treatment targets.


2020 ◽  
Author(s):  
Qiangwei Chi ◽  
Shizuan Chen ◽  
Shaotang Li

Abstract Background Colon cancer is a common tumor of the digestive tract worldwide. Recent researches have revealed that colon cancer exhibits distinct differences in clinical and biological characteristics depending on the location of the tumor. However, the underlying genetic and molecular mechanism of the differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) are not fully understood. This study aimed to identify molecular potential biomarkers and therapeutic targets for precise treatment of right-sided and left-sided colon cancer using bioinformatics analysis. Methods The gene microarray profile, named GSE44076, from the Gene Expression Omnibus (GEO) public database was downloaded and processed to then select differentially expressed genes (DEGs) on the base of two sample groups of RCC and LCC. Also, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein–protein interaction (PPI) network construction, module analysis, validation of hub genes, and survival analysis. Results Finally, we obtained 2259 DEGs between RCC and LCC, 1300 of which were upregulated in RCC and 945 of which were upregulated in LCC. The results of GO and KEGG analysis of the DEGs indicated that the biological functions of DEGs in RCC and LCC were significantly different. CTLA4, IL10, IL2RB, IFNG, NCAM1, EGFR, MYC, SRC, CUL3, and NCBP2 were identified from the PPI networks as the hub genes of RCC and LCC. Among the hub genes, the log-rank tests for overall survival (OS) and disease free survival (DFS) were applied. Moreover, all hub genes, except CUL3, had differential expression levels of miRNA between tumor group and normal group. Conclusion These hub genes and pathways identified based on bioinformatics analysis might conduce to explain the differences between RCC and LCC, and most of the hub genes were specific to the malignant tissues. Notably, these hub genes, especially the genes associated with immunotherapy such as CTLA4, might be potential specific targets or prognostic markers for precise treatment of colon cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Weishuang Xue ◽  
Jinwei Li ◽  
Kailei Fu ◽  
Weiyu Teng

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects the quality of life of elderly individuals, while the pathogenesis of AD is still unclear. Based on the bioinformatics analysis of differentially expressed genes (DEGs) in peripheral blood samples, we investigated genes related to mild cognitive impairment (MCI), AD, and late-stage AD that might be used for predicting the conversions. Methods. We obtained the DEGs in MCI, AD, and advanced AD patients from the Gene Expression Omnibus (GEO) database. A Venn diagram was used to identify the intersecting genes. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) were used to analyze the functions and pathways of the intersecting genes. Protein-protein interaction (PPI) networks were constructed to visualize the network of the proteins coded by the related genes. Hub genes were selected based on the PPI network. Results. Bioinformatics analysis indicated that there were 61 DEGs in both the MCI and AD groups and 27 the same DEGs among the three groups. Using GO and KEGG analyses, we found that these genes were related to the function of mitochondria and ribosome. Hub genes were determined by bioinformatics software based on the PPI network. Conclusions. Mitochondrial and ribosomal dysfunction in peripheral blood may be early signs in AD patients and related to the disease progression. The identified hub genes may provide the possibility for predicting AD progression or be the possible targets for treatments.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Bojun Xu ◽  
Lei Wang ◽  
Huakui Zhan ◽  
Liangbin Zhao ◽  
Yuehan Wang ◽  
...  

Objectives. Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients. Methods. GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN. Results. There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN. Conclusions. We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Fanyan Meng ◽  
Ningna Du ◽  
Daoming Xu ◽  
Li Kuai ◽  
Lanying Liu ◽  
...  

Ankylosing spondylitis (AS) is an autoimmune disease that mainly affects the spinal joints, sacroiliac joints, and adjacent soft tissues. We conducted bioinformatics analysis to explore the molecular mechanism related to AS pathogenesis and uncover novel potential molecular targets for the treatment of AS. The profiles of GSE25101, containing gene expression data extracted from the blood of 16 AS patients and 16 matched controls, were acquired from the Gene Expression Omnibus (GEO) database. The background correction and standardization were carried out utilizing the transcript per million (TPM) method. After analysis of AS patients and the normal groups, we identified 199 differentially expressed genes (DEGs) with upregulation and 121 DEGs with downregulation by the limma R package. The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analysis revealed that the DEGs with upregulation were mainly associated with spliceosome, ribosome, RNA-catabolic process, electron transport chain, etc. And the DEGs with downregulation primarily participated in T cell-associated pathways and processes. After analysis of the protein-protein interaction (PPI) network, our data revealed that the hub genes, comprising MRPL13, MRPL22, LSM3, COX7A2, COX7C, EP300, PTPRC, and CD4, could be the treatment targets in AS. Our data furnish new hints to uncover the features of AS and explore more promising treatment targets towards AS.


2020 ◽  
Vol 77 (3) ◽  
pp. 1255-1265
Author(s):  
Hui Xu ◽  
Jianping Jia

Background: The pathogenesis of Alzheimer’s disease (AD) involves various immune-related phenomena; however, the mechanisms underlying these immune phenomena and the potential hub genes involved therein are unclear. An understanding of AD-related immune hub genes and regulatory mechanisms would help develop new immunotherapeutic targets. Objective: The aim of this study was to explore the hub genes and the mechanisms underlying the regulation of competitive endogenous RNA (ceRNA) in immune-related phenomena in AD pathogenesis. Methods: We used the GSE48350 data set from the Gene Expression Omnibus database and identified AD immune-related differentially expressed RNAs (DERNAs). We constructed protein–protein interaction (PPI) networks for differentially expressed mRNAs and determined the degree for screening hub genes. By determining Pearson’s correlation coefficient and using StarBase, DIANA-LncBase, and Human MicroRNA Disease Database (HMDD), the AD immune-related ceRNA network was generated. Furthermore, we assessed the upregulated and downregulated ceRNA subnetworks to identify key lncRNAs. Results: In total, 552 AD immune-related DERNAs were obtained. Twenty hub genes, including PIK3R1, B2M, HLA-DPB1, HLA-DQB1, PIK3CA, APP, CDC42, PPBP, C3AR1, HRAS, PTAFR, RAB37, FYN, PSMD1, ACTR10, HLA-E, ARRB2, GGH, ALDOA, and VAMP2 were identified on PPI network analysis. Furthermore, upon microRNAs (miRNAs) inhibition, we identified LINC00836 and DCTN1-AS1 as key lncRNAs regulating the aforementioned hub genes. Conclusion: AD-related immune hub genes include B2M, FYN, PIK3R1, and PIK3CA, and lncRNAs LINC00836 and DCTN1-AS1 potentially contribute to AD immune-related phenomena by regulating AD-related hub genes.


2021 ◽  
Author(s):  
Tian-Ao Xie ◽  
Hou-He Li ◽  
Zu-En Lin ◽  
Xiao-Ye Lin ◽  
Xin Meng ◽  
...  

Abstract Background: The Corona Virus Disease 2019 (COVID-19) pandemic poses a serious public health threat to the survival and health of people all over the world. We analyzed related mRNA data and gene expression profiles of human cell lines infected with SARS-CoV-2 obtained from GEO (GSE148729), using bioinformatics tools. Differentially expressed genes (DEGs) of human cells infected with SARS-CoV-2 were identified.Method: The GSE148729 datasets were downloaded from the Gene Expression Omnibus (GEO) database. To explore the Biological significance of DEGs, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the DEGs was performed. Protein-protein interaction (PPI) networks of the DEGs were constructed by using the STRING database. The hub genes were selected using the Cytoscape Software, and a t-test was performed to validate the hub genes.Result: A total of 1241 DEGs were screened, including 1049 up-regulated genes and 192 down-regulated genes. Besides, 10 hub genes were obtained from the PPI network, among which the expression level of CXCL2, Etv7, and HIST1H2BG was found to be statistically significant.Conclusion: In conclusion, bioinformatics analysis reveals genes and cellular pathways that are significantly altered in SARS-CoV-2 infected cells. This is conducive to further guide the clinical study of SARS-CoV-2 and provides new perspectives for vaccine development.


2020 ◽  
Author(s):  
Huatian Luo ◽  
Da-qiu Chen ◽  
Jing-jing Pan ◽  
Zhang-wei Wu ◽  
Can Yang ◽  
...  

Abstract Background: Pancreatic cancer has many pathologic types, among which pancreatic ductal adenocarcinoma (PDAC) is the most common one. Bioinformatics has become a very common tool for the selection of potentially pathogenic genes. Methods: Three data sets containing the gene expression profiles of PDAC were downloaded from the gene expression omnibus (GEO) database. The limma package of R language was utilized to explore the differentially expressed genes (DEGs). To analyze functions and signaling pathways, the Database Visualization and Integrated Discovery (DAVID) was used. To visualize the protein-protein interaction (PPI) of the DEGs ,Cytoscape was performed under the utilization of Search Tool for the Retrieval of Interacting Genes (STRING). With the usage of the plug-in cytoHubba in cytoscape software, the hub genes were found out. To verify the expression levels of hub genes, Gene Expression Profiling Interactive Analysis (GEPIA) was performed. Last but not least, UALCAN analysis online tool was implemented to analyze the overall survival. Results: The 376 DEGs were highly enriched in biological processes including signal transduction, apoptotic process and several pathways, mainly associated with Protein digestion and absorption and Pancreatic secretion pathway. The expression levels of nucleolar and spindle associated protein 1 (NUSAP1) and SHC binding and spindle associated 1 (SHCBP1) were discovered highly expressed in pancreatic ductal adenocarcinoma tissues. NUSAP1 and SHCBP1 had a high correlation with prognosis. Conclusions: The findings of this bioinformatics analysis indicate that NUSAP1 and SHCBP1 may be key factors in the prognosis and treatment of pancreatic cancer.


2021 ◽  
Author(s):  
Pegah Einaliyan ◽  
Ali Owfi ◽  
Mohammadamin Mahmanzar ◽  
Taha Aghajanzadeh ◽  
Morteza Hadizadeh ◽  
...  

AbstractBackgroundCurrently, non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world. Forecasting the short-term, up to 2025, NASH due to fibrosis is one of the leading causes of liver transplantation. Cohort studies revealed that non-alcoholic steatohepatitis (NASH) has a higher risk of fibrosis progression among NAFLD patients. Identifying differentially expressed genes helps to determine NASH pathogenic pathways, make more accurate diagnoses, and prescribe appropriate treatment.Methods and ResultsIn this study, we found 11 NASH datasets by searching in the Gene Expression Omnibus (GEO) database. Subsequently, NASH datasets with low-quality control scores were excluded. Four datasets were analyzed with packages of R/Bioconductor. Then, all integrated genes were Imported into Cytoscape to illustrate the protein-protein interactions network. All hubs and nodes degree has been calculated to determine the hub genes with critical roles in networks.Possible correlations between expression profiles of mutual DEGs were identified employing Principal Component Analysis (PCA). Primary analyzed data were filtered based on gene expression (logFC > 1, logFC < −1) and adj-P-value (<0.05). Ultimately, among 379 DEGs, we selected the top 10 genes (MYC, JUN, EGR1, FOS, CCL2, IL1B, CXCL8, PTGS2, IL6, SERPINE1) as candidates among up and down regulated genes, and critical pathways such as IL-6, IL-17, TGF β, and TNFα were identified.ConclusionThe present study suggests an important DEGs, biological processes, and critical pathways involved in the pathogenesis of NASH disease. Further investigations are needed to clarify the exact mechanisms underlying the development and progression of NASH disease.


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