scholarly journals Bioinformatics Analysis for Identifying Pertinent Pathways and Genes in Sepsis

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yiran Li ◽  
Hongyan Zhang ◽  
Jinyan Shao ◽  
Jindong Chen ◽  
Tiancheng Zhang ◽  
...  

Purpose. Sepsis becomes the main death reason in hospitals with rising incidence, causing a growing economic and medical burden. However, the genes related to the pathogenesis and prognosis of sepsis are still unclear, which is a problem that needs to be solved urgently. Materials and Methods. Gene expression profiles of GSE69528 were obtained from the National Center for Biotechnology Information. Limma software package got employed to search for differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used for enrichment analysis. Protein-protein interaction (PPI) network was built by the Search Tool for the Retrieval of Interacting Genes (STRING) database. Results. We screened 101 DEGs, containing 81 upregulated DEGs and 20 downregulated DEGs. GO analysis demonstrated that the upregulated DEGs were chiefly concentrated in negative regulation of response to interferon-gamma and regulation of granulocyte differentiation. KEGG analysis revealed that the pathways of upregulated DEGs were concentrated in prion diseases, complement and coagulation cascades, and Staphylococcus aureus infection. The PPI network constructed by upregulated DEGs contained 67 nodes (proteins) and 110 edges (interactions). Analysis of bioinformatics results showed that CEACAM8, MPO, and RETN were hub genes of sepsis. Conclusion. Our analysis reveals a series of signal pathways and key genes related to the mechanism of sepsis, which are promising biotargets and biomarkers of sepsis.

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):  
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.


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.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Bi-Qing Li ◽  
Jin You ◽  
Lei Chen ◽  
Jian Zhang ◽  
Ning Zhang ◽  
...  

Lung cancer is one of the leading causes of cancer mortality worldwide. The main types of lung cancer are small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC). In this work, a computational method was proposed for identifying lung-cancer-related genes with a shortest path approach in a protein-protein interaction (PPI) network. Based on the PPI data from STRING, a weighted PPI network was constructed. 54 NSCLC- and 84 SCLC-related genes were retrieved from associated KEGG pathways. Then the shortest paths between each pair of these 54 NSCLC genes and 84 SCLC genes were obtained with Dijkstra’s algorithm. Finally, all the genes on the shortest paths were extracted, and 25 and 38 shortest genes with a permutationPvalue less than 0.05 for NSCLC and SCLC were selected for further analysis. Some of the shortest path genes have been reported to be related to lung cancer. Intriguingly, the candidate genes we identified from the PPI network contained more cancer genes than those identified from the gene expression profiles. Furthermore, these genes possessed more functional similarity with the known cancer genes than those identified from the gene expression profiles. This study proved the efficiency of the proposed method and showed promising results.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Gao ◽  
Yu Zhao ◽  
Xuelei Ma ◽  
Ling Zhang

Abstract Background Competitive endogenous RNA (ceRNA) networks have revealed a new mechanism of interaction between RNAs, and play crucial roles in multiple biological processes and development of neoplasms. They might serve as diagnostic and prognosis markers as well as therapeutic targets. Methods In this work, we identified differentially expressed mRNAs (DEGs), lncRNAs (DELs) and miRNAs (DEMs) in sarcomas by comparing the gene expression profiles between sarcoma and normal muscle samples in Gene Expression Omnibus (GEO) datasets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were applied to investigate the primary functions of the overlapped DEGs. Then, lncRNA-miRNA and miRNA-mRNA interactions were predicted, and the ceRNA regulatory network was constructed using Cytoscape software. In addition, the protein–protein interaction (PPI) network and survival analysis were performed. Results A total of 1296 DEGs were identified in sarcoma samples by combining the GO and KEGG enrichment analyses, 338 DELs were discovered after the probes were reannotated, and 36 DEMs were ascertained through intersecting two different expression miRNAs sets. Further, through target gene prediction, a lncRNA–miRNA–mRNA ceRNA network that contained 113 mRNAs, 69 lncRNAs and 29 miRNAs was constructed. The PPI network identified the six most significant hub proteins. Survival analysis revealed that seven mRNAs, four miRNAs and one lncRNA were associated with overall survival of sarcoma patients. Conclusions Overall, we constructed a ceRNA network in sarcomas, which might provide insights for further research on the molecular mechanism and potential prognosis biomarkers.


2021 ◽  
Vol 24 (5-6) ◽  
pp. 267-279
Author(s):  
Xianyang Zhu ◽  
Wen Guo

<b><i>Background:</i></b> This study aimed to screen and validate the crucial genes involved in osteoarthritis (OA) and explore its potential molecular mechanisms. <b><i>Methods:</i></b> Four expression profile datasets related to OA were downloaded from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) from 4 microarray patterns were identified by the meta-analysis method. The weighted gene co-expression network analysis (WGCNA) method was used to investigate stable modules most related to OA. In addition, a protein-protein interaction (PPI) network was built to explore hub genes in OA. Moreover, OA-related genes and pathways were retrieved from Comparative Toxicogenomics Database (CTD). <b><i>Results:</i></b> A total of 1,136 DEGs were identified from 4 datasets. Based on these DEGs, WGCNA further explored 370 genes included in the 3 OA-related stable modules. A total of 10 hub genes were identified in the PPI network, including <i>AKT1</i>, <i>CDC42</i>, <i>HLA-DQA2</i>, <i>TUBB</i>, <i>TWISTNB</i>, <i>GSK3B</i>, <i>FZD2</i>, <i>KLC1</i>, <i>GUSB</i>, and <i>RHOG</i>. Besides, 5 pathways including “Lysosome,” “Pathways in cancer,” “Wnt signaling pathway,” “ECM-receptor interaction” and “Focal adhesion” in CTD and enrichment analysis and 5 OA-related hub genes (including <i>GSK3B, CDC42, AKT1, FZD2</i>, and <i>GUSB</i>) were identified. <b><i>Conclusion:</i></b> In this study, the meta-analysis was used to screen the central genes associated with OA in a variety of gene expression profiles. Three OA-related modules (green, turquoise, and yellow) containing 370 genes were identified through WGCNA. It was discovered through the gene-pathway network that <i>GSK3B, CDC42, AKT1, FZD2</i>, <i>and GUSB</i> may be key genes related to the progress of OA and may become promising therapeutic targets.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7067
Author(s):  
Mohammed Khamis Miraji ◽  
Yichun Cheng ◽  
Shuwang Ge ◽  
Gang Xu

The current study is aimed to explore the specific genes which are responsible for the manifestation of Immunoglobulin A nephropathy (IgAN). Gene expression profiles GSE37460, GSE93798 and GSE104948 were analyzed using biological informatics methods to identify differentially expressed genes (DEGs) in IgAN glomeruli samples which were then compared to normal control samples. Subsequently, the DEGs were overlapped to explore genes with significant expression in at least two profiles. Finally, the enrichment analysis was conducted and the protein-protein interaction (PPI) network was constructed for the overlapping DEGs. A total of 28 genes were up-regulated and 10 genes were down-regulated. The up-regulated genes including CD44 and FN1 were chiefly involved in extracellular matrix receptors interaction pathway. In addition, CX3CR1 and CCL4 were associated with chemokine signaling pathway. ITGB2, PTPRC, FN1, and FCER1G were hub genes with a high degree of interaction in the PPI network. Therefore, this study identified many significant genes associated with extracellular matrix expansion and inflammatory mechanism which may be the novel biomarker and target candidates in IgAN.


2019 ◽  
Vol 16 (5) ◽  
pp. 415-426
Author(s):  
Cheng-Wen Yang ◽  
Huan-Huan Cao ◽  
Yu Guo ◽  
Yuan-Ming Feng ◽  
Ning Zhang

Background:Breast cancer is one of the most common malignancies, and a threat to female health all over the world. However, the molecular mechanism of breast cancer has not been fully discovered yet.Objective:It is crucial to identify breast cancer-related genes, which could provide new biomarker for breast cancer diagnosis as well as potential treatment targets.Methods:Here we used the minimum redundancy-maximum relevance (mRMR) method to select significant genes, then mapped the transcripts of the genes on the Protein-Protein Interaction (PPI) network and traced the shortest path between each pair of two proteins.Results:As a result, we identified 24 breast cancer-related genes whose betweenness were over 700. The GO enrichment analysis indicated that the transcription and oxygen level are very important in breast cancer. And the pathway analysis indicated that most of these 24 genes are enriched in prostate cancer, endocrine resistance, and pathways in cancer.Conclusion:We hope these 24 genes might be useful for diagnosis, prognosis and treatment for breast cancer.


2020 ◽  
Author(s):  
Yunwen Cui ◽  
Cheng Liu ◽  
Jian Luo ◽  
Jie Liang

Abstract Background Hypertrophic cardiomyopathy (HCM) is a group of heterogeneous diseases that affect the myocardium. It is also a common familial disease. The symptoms are not common and easy to find. Methods In this study, gene expression profiles of 37 samples (GSE130036) were downloaded from GEO database. Differential analysis was used to identify the related dysregulated genes in patients with HCM. Enrichment analysis identified the biological function and signal pathway of these differentially expressed genes. Then, we build PPI network and verify it in GSE36961 dataset. Finally, the gene of single nuclear variants (SNVs) in HCM samples was screened by means of maftools. Results Herein, we obtained 920 differentially expressed genes, and found that these genes are mainly related to metabolic related signaling pathways. 187 interacting genes were identified by PPI network analysis, and the expression trends of C1QB, F13A1, CD163, FCN3, PLA2G2A and CHRDL2 were verified by another dataset. ROC curve analysis showed that they had certain clinical diagnostic ability, and they were the potential key dysfunctional genes of HCM. In addition, we found that PRMT5 mutation was the most frequent in HCM samples, which may affect the pathogenesis of HCM. Conclusions Therefore, the key genes and enrichment results identified by our analysis may provide a reference for the occurrence and development mechanism of HCM. In addition, mutations in PRMT5 may be a useful therapeutic and diagnostic target for HCM.


Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090753
Author(s):  
Tianlong Wu ◽  
Honghai Cao ◽  
Lei Liu ◽  
Kan Peng

Background: The risk of malignant transformation of enchondromas (EC) toward central chondrosarcoma is increased up to 35%, while the exact etiology of EC is unknown. The purpose of this research was to authenticate gene signatures during EC and reveal their potential mechanisms in occurrence and development of EC. Methods: The gene expression profiles was acquired from Gene Expression Omnibus database (no. GSE22855). The gene ontology (GO), protein–protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were utilized to identify differentially expressed genes (DEGs). Results: Finally, 242 DEGs were appraisal, containing 200 overregulated genes and 42 downregulated genes. The outcomes of GO analysis indicated that upregulated DEGs were mainly enriched in several biological processes containing response to hypoxia, calcium ion, and negative regulation extrinsic apoptotic signaling pathway. Furthermore, the upregulated DEGs were enriched in extracellular matrix (ECM)–receptor interaction, protein processing in endoplasmic reticulum and ribosome, which was analyzed by KEGG pathway. From the PPI network, the top 10 hub genes were identified, which were related to significant pathways containing ribosome, protein processing in endoplasmic reticulum, and ECM-receptor interaction. Conclusion: In conclusion, the present study may be helpful for understanding the diagnostic biomarkers of EC.


Sign in / Sign up

Export Citation Format

Share Document