scholarly journals Identification of Key Genes and Pathways in SARS-CoV-2 Infection using Bioinformatics Analysis

2020 ◽  
Author(s):  
Zhe Wang ◽  
Chenhao Jiang ◽  
Xuxuan Zhang ◽  
Yingna Zhang ◽  
Yan Ren ◽  
...  

Abstract Background: Coronavirus disease 2019 (COVID-19) is a disease that causes fatal disorders including severe pneumonia. Our study aimed to utilize bioinformatics method to analyze the expression profiling by high throughput sequencing in human bronchial organoids/primary human airway epithelial infected with SARS-CoV-2 to identify the potentially crucial genes and pathways associated with COVID-19.Methods: We analyzed microarray datasets GSE153970 and GSE150819 derived from the GEO database. Firstly, the Differentially expressed genes (DEGs) in human bronchial organoids/primary human airway epithelial infected with SARS-CoV-2. Next, the DEGs were used for GO and KEGG pathway enrichment analysis. Then, the PPI network was constructed and Cytoscape was used to find the key genes.Results: Gene expression profiles of GSE153970 and GSE150819, in all 12 samples were analyzed. A total of 145 DEGs and 5 hub genes were identified in SARS-CoV-2. Meanwhile, we found that the 145 genes are associated with immune responses and the top 5 hub genes including CXCL8, CXCL1, CXCL2, CCL20, and CSF2 were mainly related to leukocyte migration, endoplasmic reticulum lumen, receptor ligand activity. In addition, the results also showed that the hub genes were associated with Cytokine−cytokine receptor interaction, IL−17 signaling pathway, and Rheumatoid arthritis in SARS-CoV-2 infection.Conclusion: The five crucial genes consisting of CXCL8, CXCL1, CXCL2, CCL20, and CSF2 were considered as hub genes of SARS-CoV-2, which may be used as diagnostic biomarkers or molecular targets for the treatment of SARS-CoV-2. It is evidenced that bioinformatics analyses in SARS-CoV-2 can be useful for understanding the underlying molecular mechanism and exploring effective therapeutic targets.

2021 ◽  
Author(s):  
Weina Lu ◽  
Ran Ji

Abstract Background and Aims: Acute respiratory distress syndrome (ARDS) is one of the most common acute thoracopathy with complicated pathogenesis in ICU. The study is to explore the differentially expressed genes (DEGs) in the lung tissue and underlying altering mechanisms in ARDS.Methods: Gene expression profiles of GSE2411 and GSE130936 were available from GEO database, both of them included in GPL 339. Then, an integrated analysis of these genes was performed, including gene ontology (GO) and KEGG pathway enrichment analysis, protein-protein interaction (PPI) network construction, Transcription Factors (TFs) forecasting, and their expression in varied organs.Results: A total of 39 differential expressed genes were screened from the datasets, including 39 up-regulated genes and 0 down-regulated genes. The up-regulated genes were mainly enriched in the biological process, such as immune system process, innate immune response, inflammatory response, cellular response to interferon-beta and also involved in some signal pathways, including cytokine-cytokine receptor interaction, salmonella infection, legionellosis, chemokine, and Toll-like receptor signal pathway. GBP2, IFIT2 and IFIT3 were identified as hub genes in the lung by PPI network analysis with MCODE plug-in, as well as GO and KEGG re-enrichment. All of the three hub genes were regulated by the predictive common TFs, including STAT1, E2F1, IRF1, IRF2, and IRF9. Conclusions: This study implied that hub gene GBP2, IFIT2 and IFIT3, which might be regulated by STAT1, E2F1, IRF1, IRF2, or IRF9, played significant roles in ARDS. They could be potential diagnostic or therapeutic targets for ARDS patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Weina Lu ◽  
Ran Ji

Abstract Background and aims Acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) is one of the most common acute thoracopathy with complicated pathogenesis in ICU. The study is to explore the differentially expressed genes (DEGs) in the lung tissue and underlying altering mechanisms in ARDS. Methods Gene expression profiles of GSE2411 and GSE130936 were available from GEO database, both of them included in GPL339. Then, an integrated analysis of these genes was performed, including gene ontology (GO) and KEGG pathway enrichment analysis in DAVID database, protein–protein interaction (PPI) network construction evaluated by the online database STRING, Transcription Factors (TFs) forecasting based on the Cytoscape plugin iRegulon, and their expression in varied organs in The Human Protein Atlas. Results A total of 39 differential expressed genes were screened from the two datasets, including 39 up-regulated genes and 0 down-regulated genes. The up-regulated genes were mainly enriched in the biological process, such as immune system process, innate immune response, inflammatory response, and also involved in some signal pathways, including cytokine–cytokine receptor interaction, Salmonella infection, Legionellosis, Chemokine, and Toll-like receptor signal pathway with an integrated analysis. GBP2, IFIT2 and IFIT3 were identified as hub genes in the lung by PPI network analysis with MCODE plug-in, as well as GO and KEGG re-enrichment. All of the three hub genes were regulated by the predictive common TFs, including STAT1, E2F1, IRF1, IRF2, and IRF9. Conclusions This study implied that hub gene GBP2, IFIT2 and IFIT3, which might be regulated by STAT1, E2F1, IRF1, IRF2, or IRF9, played significant roles in ARDS. They could be potential diagnostic or therapeutic targets for ARDS patients.


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):  
Perumal Jayaraj ◽  
Seema Sen ◽  
Pranjal Vats ◽  
Shefali Dahiya ◽  
Vanshika Mohindroo

Background: Eyelid BCC accounts for more than 90% of Eyelid malignant neoplasms. Various aberrant signalling pathways and genes in Non-Ocular BCC have been found whereas Eyelid bcc remains elusive. Objective: This study aims to find the common DEGs of Eyelid and Non-Ocular BCC using bioinformatic analysis and text mining to gain more insights into the molecular aspects common to both BCC non-ocular and Eyelid BCC and to identify common potential prognostic markers. Material and method: The Gene Expression profiles of Eyelid BCC (GSE103439) and Non-Ocular BCC (GSE53462) were obtained from the NCBI GEO database followed by identification of common DEGs. Protein-Protein interaction and Pathway Enrichment analysis of these screened genes was done using bioinformatic tools like STRING, Cytoscape and BiNGO, DAVID, KEGG respectively. Results: A total of 181 genes were found common in both datasets. A PPI network was formed for the screened genes and 20 HUB genes were sorted which included CTNNB1, MAPK14, BTRC, EGFR, ADAM17. Pathway enrichment of HUB genes showed that they were dysregulated in carcinogenic and apoptotic pathways that seem to play a role in the progression of both the BCC. Conclusion: The result and findings of bioinformatic analysis highlighted the molecular pathways and genes enriched in both Eyelid BCC as well as Non- Ocular BCC. The identified pathways should be studied further to recognise common molecular events that would lead to the progression of BCC. This may provide a window to explore the prognostic and therapeutic strategies common to both BCC. Keywords: Basal cell carcinoma (BCC), Cancer, Microarray, Ophthalmology, Tumour marker


2021 ◽  
pp. 153537022110487
Author(s):  
Zirui Zhu ◽  
Rui Huang ◽  
Baojun Huang

Gastric cancer (GC) remains one of the most prevalent types of malignancies worldwide, and also one of the most reported lethal tumor-related diseases. Circular RNAs (circRNAs) have been certified to be trapped in multiple aspects of GC pathogenesis. Yet, the mechanism of this regulation is mostly undefined. This research is designed to discover the vital circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in GC. Expression profiles with diverse levels including circRNAs, miRNAs, and mRNAs were all determined using microarray public datasets from Gene Expression Ominous (GEO). The differential circRNAs expressions were recognized against the published robust rank aggregation algorithm. Besides, a circRNA-based competitive endogenous RNA (ceRNA) interaction network was visualized via Cytoscape software (version 3.8.0). Functional and pathway enrichment analysis associated with differentially expressed targeted mRNAs were conducted using Cytoscape and an online bioinformatics database. Furthermore, an interconnected protein–protein interaction association network which consisted of 51 mRNAs was predicted, and hub genes were screened using STRING and CytoHubba. Then, several hub genes were chosen to explore their expression associated with survival rate and clinical stage in GEPIA and Kaplan-Meier Plotter databases. Finally, a carefully designed circRNA-related ceRNA regulatory subnetwork including four circRNAs, six miRNAs, and eight key hub genes was structured using the online bioinformatics tool.


2020 ◽  
Author(s):  
Basavaraj Vastrad ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti

AbstractSporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. Pathway and GO enrichment analyses of DEGs were performed. Furthermore, the protein-protein interaction (PPI) network was predicted using the IntAct Molecular Interaction Database and visualized with Cytoscape software. In addition, hub genes and important modules were selected based on the network. Finally, we constructed target genes - miRNA regulatory network and target genes - TF regulatory network. Hub genes were validated. A total of 891 DEGs 448 of these DEGs presented significant up regulated, and the remaining 443 down regulated were obtained. Pathway enrichment analysis indicated that up regulated genes were mainly linked with glutamine degradation/glutamate biosynthesis, while the down regulated genes were involved in melatonin degradation. GO enrichment analyses indicated that up regulated genes were mainly linked with chemical synaptic transmission, while the down regulated genes were involved in regulation of immune system process. hub and target genes were selected from the PPI network, modules, and target genes - miRNA regulatory network and target genes - TF regulatory network namely YWHAZ, GABARAPL1, EZR, CEBPA, HSPB8, TUBB2A and CDK14. The current study sheds light on the molecular mechanisms of sCJD and may provide molecular targets and diagnostic biomarkers for sCJD.


2018 ◽  
Vol 96 (8) ◽  
pp. 701-709 ◽  
Author(s):  
Jing Gao ◽  
Yuhong Li ◽  
Tongmei Wang ◽  
Zhuo Shi ◽  
Yiqi Zhang ◽  
...  

The aim of this study was to identify the key genes involved in the cardiac hypertrophy (CH) induced by pressure overload. mRNA microarray data sets GSE5500 and GSE18801 were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were screened using the Limma package; then, functional and pathway enrichment analysis were performed for common DEGs using the Database for Annotation, Visualization and Integrated Discovery database. Furthermore, the top DEGs were further validated using quantitative PCR in the hypertrophic heart tissue induced by isoprenaline. A total of 113 common DEGs with absolute fold change > 0.5, including 60 significantly upregulated DEGs and 53 downregulated DEGs, were obtained. Gene ontology term enrichment analysis suggested that common upregulated DEG were mainly enriched in neutrophil chemotaxis, extracellular fibril organization, and cell proliferation; and the common downregulated genes were significantly enriched in ion transport, endoplasmic reticulum, and dendritic spine. Kyoto Encyclopedia of Genes and Genomes pathway analysis found that the common DEGs were mainly enriched in extracellular matrix receptor interaction, phagosome, and focal adhesion. Additionally, the expression of Mfap4, Ltbp2, Aspn, Serpina3n, and Cnksr1 were upregulated in the model of CH, while the expression of Anp32a was downregulated. The current study identified the key deregulated genes and pathways involved in the CH, which could shed new light to understand the mechanism of CH.


2021 ◽  
Author(s):  
Kainan Lin ◽  
Zhenyan Pan ◽  
Renke He ◽  
Hanchu Wang ◽  
Kai Zhou ◽  
...  

Abstract Purpose Endometriosis is a common gynaecological disease; however, the specific mechanism and the key molecules involved in endometriosis have not been elucidated. This study aimed to identify key genes associated with poor prognosis and further uncover underlying mechanisms. Methods Data regarding mRNA expression profiles used in this study were retrieved from the Gene Expression Omnibus (GEO) database, and a total of three mRNA expression profiles were included in subsequent analyses (GSE31515, GSE58178 and GSE120103). We divided all differentially expressed genes (DEGs) into up-regulated and down-regulated groups. Then, we conducted Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) analysis using R software.Results A total of 304 DEGs were identified between endometriosis tissues and normal endometrium tissues using integrated analysis, including 185 up-regulated genes and 119 down-regulated genes. GO analysis revealed that the up-regulated DEGs of endometriosis were closely associated with voltage-gated calcium channel activity, whereas the down-regulated DEGs were enriched in uterus development. KEGG pathway enrichment analysis indicated that the up-regulated DEGs were mainly involved in cytokine-cytokine receptor interaction, whereas down-regulated DEGs were enriched in protein processing in the endoplasmic reticulum. In addition, PPIs of these DEGs were visualized using the Cytoscape platform and the Search Tool for the Retrieval of Interacting Genes (STRING). PPI analysis identified 10 potential DEG-related protein targets, including CCND1, IL6, CCL2, COL1A2, PTGS2, VCAM1, COL3A1, ELN, SERPINE1, and HSP90B1. Conclusion In conclusion, the present study reveals that voltage-gated calcium channel activity, uterus development, cytokine-cytokine receptor interaction and protein processing in the endoplasmic reticulum may be involved in the development of endometriosis. In addition, these identified DEGs may exhibit clinical significance for the diagnosis and treatment of endometriosis.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yanmin Lyu ◽  
Xiangjing Chen ◽  
Qing Xia ◽  
Shanshan Zhang ◽  
Chengfang Yao

Background. Pinellia ternata (PT), a medicinal plant, has had an extensive application in the treatment of asthma in China, whereas its underlying pharmacological mechanisms remain unclear. Methods. Firstly, a network pharmacology method was adopted to collect activated components of PT from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets of PT were assessed by exploiting the PharmMapper website; asthma-related targets were collected from the OMIM website, and target-target interaction networks were built. Secondly, critical nodes exhibiting high possibility were identified as the hub nodes in the network, which were employed to conduct Gene Ontology (GO) comment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the tissue expression profiles of key candidate genes were identified by the Gene Expression Omnibus (GEO) database, and the therapeutic effect of PT was verified by an animal experiment. Results. 57 achievable targets of PT on asthma were confirmed as hub nodes through using the network pharmacology method. As revealed from the KEGG enrichment analysis, the signaling pathways were notably enriched in pathways of the T-cell receptor signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction. The expression profiles of candidate genes including Mmp2, Nr3c1, il-10, il-4, il-13, il-17a, il-2, tlr4, tlr9, ccl2, csf2, and vefgα were identified. Moreover, according to transcriptome RNA sequencing data from lung tissues of allergic mice compared to normal mice, the mRNA level of Mmp2 and il-4 was upregulated ( P < 0.001 ). In animal experiments, PT could alleviate the allergic response of mice by inhibiting the activation of T-helper type 2 (TH2) cells and the expression of Mmp2 and il-4. Conclusions. Our study provides candidate genes that may be either used for future studies related to diagnosis/prognosis or as targets for asthma management. Besides, animal experiments showed that PT could treat asthma by regulating the expression of Mmp2 and il-4.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xingsheng Liu ◽  
Kun Qian ◽  
Gaojun Lu ◽  
Peng Chen ◽  
Yi Zhang

Abstract Background Malignant pleural mesothelioma (MPM) is a rare tumor in the pleura. This study was carried out to identify key genes and pathways that may be involved in MPM. Methods Microarray datasets GSE51024 and GSE2549 were analyzed for differentially expressed genes (DEGs) between normal and MPM tissues. The identified DEGs were subjected to functional analyses using bioinformatics tools. Results A total of 276 DEGs were identified, consisting of 187 downregulated and 79 upregulated genes. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis indicated that the DEGs were enriched in extracellular structure organization, extracellular matrix, and ECM−receptor interaction. Due to high degree of connectivity among 24 hub genes, EZH2 and HMMR are likely to play roles in the carcinogenesis and progression of MPM. The two genes were found over-expressed in MPM tissues. Patients with elevated EZH2 and HMMR expressions had poor overall survival. Conclusions EZH2 and HMMR are identified to be the hub genes for MPM and they may be further characterized to better understand the molecular mechanisms underlying the carcinogenesis of MPM.


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