scholarly journals Identification of Key Genes Involved in Acute Myocardial Infarction by Comparative Transcriptome Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiaodong Sheng ◽  
Tao Fan ◽  
Xiaoqi Jin

Background. Acute myocardial infarction (AMI) is regarded as an urgent clinical entity, and identification of differentially expressed genes, lncRNAs, and altered pathways shall provide new insight into the molecular mechanisms behind AMI. Materials and Methods. Microarray data was collected to identify key genes and lncRNAs involved in AMI pathogenesis. The differential expression analysis and gene set enrichment analysis (GSEA) were employed to identify the upregulated and downregulated genes and pathways in AMI. The protein-protein interaction network and protein-RNA interaction analysis were utilized to reveal key long noncoding RNAs. Results. In the present study, we utilized gene expression profiles of circulating endothelial cells (CEC) from 49 patients of AMI and 50 controls and identified a total of 552 differentially expressed genes (DEGs). Based on these DEGs, we also observed that inflammatory response-related genes and pathways were highly upregulated in AMI. Mapping the DEGs to the protein-protein interaction (PPI) network and identifying the subnetworks, we found that OMD and WDFY3 were the hub nodes of two subnetworks with the highest connectivity, which were found to be involved in circadian rhythm and organ- or tissue-specific immune response. Furthermore, 23 lncRNAs were differentially expressed between AMI and control groups. Specifically, we identified some functional lncRNAs, including XIST and its antisense RNA, TSIX, and three lncRNAs (LINC00528, LINC00936, and LINC01001), which were predicted to be interacting with TLR2 and participate in Toll-like receptor signaling pathway. In addition, we also employed the MMPC algorithm to identify six gene signatures for AMI diagnosis. Particularly, the multivariable SVM model based on the six genes has achieved a satisfying performance ( AUC = 0.97 ). Conclusion. In conclusion, we have identified key regulatory lncRNAs implicated in AMI, which not only deepens our understanding of the lncRNA-related molecular mechanism of AMI but also provides computationally predicted regulatory lncRNAs for AMI researchers.

2021 ◽  
Vol 20 ◽  
pp. 153303382098329
Author(s):  
Yujie Weng ◽  
Wei Liang ◽  
Yucheng Ji ◽  
Zhongxian Li ◽  
Rong Jia ◽  
...  

Human epidermal growth factor 2 (HER2)+ breast cancer is considered the most dangerous type of breast cancers. Herein, we used bioinformatics methods to identify potential key genes in HER2+ breast cancer to enable its diagnosis, treatment, and prognosis prediction. Datasets of HER2+ breast cancer and normal tissue samples retrieved from Gene Expression Omnibus and The Cancer Genome Atlas databases were subjected to analysis for differentially expressed genes using R software. The identified differentially expressed genes were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses followed by construction of protein-protein interaction networks using the STRING database to identify key genes. The genes were further validated via survival and differential gene expression analyses. We identified 97 upregulated and 106 downregulated genes that were primarily associated with processes such as mitosis, protein kinase activity, cell cycle, and the p53 signaling pathway. Visualization of the protein-protein interaction network identified 10 key genes ( CCNA2, CDK1, CDC20, CCNB1, DLGAP5, AURKA, BUB1B, RRM2, TPX2, and MAD2L1), all of which were upregulated. Survival analysis using PROGgeneV2 showed that CDC20, CCNA2, DLGAP5, RRM2, and TPX2 are prognosis-related key genes in HER2+ breast cancer. A nomogram showed that high expression of RRM2, DLGAP5, and TPX2 was positively associated with the risk of death. TPX2, which has not previously been reported in HER2+ breast cancer, was associated with breast cancer development, progression, and prognosis and is therefore a potential key gene. It is hoped that this study can provide a new method for the diagnosis and treatment of HER2 + breast cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Siyu Guo ◽  
Zhihong Huang ◽  
Xinkui Liu ◽  
Jingyuan Zhang ◽  
Peizhi Ye ◽  
...  

Acute coronary syndrome (ACS) is a complex syndrome of clinical symptoms. In order to accurately diagnose the type of disease in ACS patients, this study is aimed at exploring the differentially expressed genes (DEGs) and biological pathways between acute myocardial infarction (AMI) and unstable angina (UA). The GSE29111 and GSE60993 datasets containing microarray data from AMI and UA patients were downloaded from the Gene Expression Omnibus (GEO) database. DEG analysis of these 2 datasets is performed using the “limma” package in R software. DEGs were also analyzed using protein-protein interaction (PPI), Molecular Complex Detection (MCODE) algorithm, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Correlation analysis and “cytoHubba” were used to analyze the hub genes. A total of 286 DEGs were obtained from GSE29111 and GSE60993, including 132 upregulated genes and 154 downregulated genes. Subsequent comprehensive analysis identified 20 key genes that may be related to the occurrence and development of AMI and UA and were involved in the inflammatory response, interaction of neuroactive ligand-receptor, calcium signaling pathway, inflammatory mediator regulation of TRP channels, viral protein interaction with cytokine and cytokine receptor, human cytomegalovirus infection, and cytokine-cytokine receptor interaction pathway. The integrated bioinformatical analysis could improve our understanding of DEGs between AMI and UA. The results of this study might provide a new perspective and reference for the early diagnosis and treatment of ACS.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7135 ◽  
Author(s):  
Fangcao Lei ◽  
Han Zhang ◽  
Xiaoli Xie

Background Pulpitis is a common inflammatory disease that affects dental pulp. It is important to understand the molecular signals of inflammation and repair associated with this process. Increasing evidence has revealed that long noncoding RNAs (lncRNAs), via competitively sponging microRNAs (miRNAs), can act as competing endogenous RNAs (ceRNAs) to regulate inflammation and reparative responses. The aim of this study was to elucidate the potential roles of lncRNA, miRNA and messenger RNA (mRNA) ceRNA networks in pulpitis tissues compared to normal control tissues. Methods The oligo and limma packages were used to identify differentially expressed lncRNAs and mRNAs (DElncRNAs and DEmRNAs, respectively) based on expression profiles in two datasets, GSE92681 and GSE77459, from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) networks and modules were established to screen hub genes using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the Molecular Complex Detection (MCODE) plugin for Cytoscape, respectively. Furthermore, an lncRNA-miRNA-mRNA-hub genes regulatory network was constructed to investigate mechanisms related to the progression and prognosis of pulpitis. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify critical lncRNAs that may significantly affect the pathogenesis in inflamed and normal human dental pulp. Results A total of 644 upregulated and 264 downregulated differentially expressed genes (DEGs) in pulpitis samples were identified from the GSE77459 dataset, while 8 up- and 19 downregulated probes associated with lncRNA were identified from the GSE92681 dataset. Protein–protein interaction (PPI) based on STRING analysis revealed a network of DEGs containing 4,929 edges and 623 nodes. Upon combined analysis of the constructed PPI network and the MCODE results, 10 hub genes, including IL6, IL8, PTPRC, IL1B, TLR2, ITGAM, CCL2, PIK3CG, ICAM1, and PIK3CD, were detected in the network. Next, a ceRNA regulatory relationship consisting of one lncRNA (PVT1), one miRNA (hsa-miR-455-5p) and two mRNAs (SOCS3 and PLXNC1) was established. Then, we constructed the network in which the regulatory relationship between ceRNA and hub genes was summarized. Finally, our qRT-PCR results confirmed significantly higher levels of PVT1 transcript in inflamed pulp than in normal pulp tissues (p = 0.03). Conclusion Our study identified a novel lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of pulpitis.


2021 ◽  
Author(s):  
Chengang Guo ◽  
Zhimin wei ◽  
Wei Lyu ◽  
Yanlou Geng

Abstract Quinoa saponins have complex, diverse and evident physiologic activities. However, the key regulatory genes for quinoa saponin metabolism are not yet well studied. The purpose of this study was to explore genes closely related to quinoa saponin metabolism. In this study, the significantly differentially expressed genes in yellow quinoa were firstly screened based on RNA-seq technology. Then, the key genes for saponin metabolism were selected by gene set enrichment analysis (GSEA) and principal component analysis (PCA) statistical methods. Finally, the specificity of the key genes was verified by hierarchical clustering. The results of differential analysis showed that 1654 differentially expressed genes were achieved after pseudogenes deletion. Therein, there were 142 long non-coding genes and 1512 protein-coding genes. Based on GSEA analysis, 116 key candidate genes were found to be significantly correlated with quinoa saponin metabolism. Through PCA dimension reduction analysis, 57 key genes were finally obtained. Hierarchical cluster analysis further demonstrated that these key genes can clearly separate the four groups of samples. The present results could provide references for the breeding of sweet quinoa and would be helpful for the rational utilization of quinoa saponins.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yanyan Li ◽  
Jiqin Wang ◽  
Yuzhen Li ◽  
Chunyan Liu ◽  
Xia Gong ◽  
...  

Background. Immunosuppression has a key function in sepsis pathogenesis, so it is of great significance to find immune-related markers for the treatment of sepsis. Methods. Datasets of community-acquired pneumonia (CAP) with sepsis from the ArrayExpress database were extracted. Differentially expressed genes (DEGs) between the CAP group and normal group by Limma package were performed. After calculation of immune score through the ESTIMATE algorithm, the DEGs were selected between the high immune score group and the low immune score group. Enrichment analysis of the intersected DEGs was conducted. Further, the protein-protein interaction (PPI) of the intersected DEGs was drawn by Metascape tools. Related publications of the key DEGs were searched in NCBI PubMed through Biopython models, and RT-qPCR was used to verify the expression of key genes. Results. 360 intersected DEGs (157 upregulated and 203 downregulated) were obtained between the two groups. Meanwhile, the intersected DEGs were enriched in 157 immune-related terms. The PPI of the DEGs was performed, and 8 models were obtained. In sepsis-related research, eight genes were obtained with degree ≥ 10 , included in the models. Conclusion. CXCR3, CCR7, HLA-DMA, and GPR18 might participate in the mechanism of CAP with sepsis.


2015 ◽  
Vol 4 (4) ◽  
pp. 35-51 ◽  
Author(s):  
Bandana Barman ◽  
Anirban Mukhopadhyay

Identification of protein interaction network is very important to find the cell signaling pathway for a particular disease. The authors have found the differentially expressed genes between two sample groups of HIV-1. Samples are wild type HIV-1 Vpr and HIV-1 mutant Vpr. They did statistical t-test and found false discovery rate (FDR) to identify the genes increased in expression (up-regulated) or decreased in expression (down-regulated). In the test, the authors have computed q-values of test to identify minimum FDR which occurs. As a result they found 172 differentially expressed genes between their sample wild type HIV-1 Vpr and HIV-1 mutant Vpr, R80A. They found 68 up-regulated genes and 104 down-regulated genes. From the 172 differentially expressed genes the authors found protein-protein interaction network with string-db and then clustered (subnetworks) the PPI networks with cytoscape3.0. Lastly, the authors studied significance of subnetworks with performing gene ontology and also studied the KEGG pathway of those subnetworks.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yan Li ◽  
Xiao_nan He ◽  
Chao Li ◽  
Ling Gong ◽  
Min Liu

Background. Identification of potential molecular targets of acute myocardial infarction is crucial to our comprehensive understanding of the disease mechanism. However, studies of gene coexpression analysis via jointing multiple microarray data of acute myocardial infarction still remain restricted. Methods. Microarray data of acute myocardial infarction (GSE48060, GSE66360, GSE97320, and GSE19339) were downloaded from Gene Expression Omnibus database. Three data sets without heterogeneity (GSE48060, GSE66360, and GSE97320) were subjected to differential expression analysis using MetaDE package. Differentially expressed genes having upper 25% variation across samples were imported in weighted gene coexpression network analysis. Functional and pathway enrichment analyses were conducted for genes in the most significant module using DAVID. The predicted microRNAs to regulate target genes in the most significant module were identified using TargetScan. Moreover, subpathway analyses using iSubpathwayMiner package and GenCLiP 2.0 were performed on hub genes with high connective weight in the most significant module. Results. A total of 1027 differentially expressed genes and 33 specific modules were screened out between acute myocardial infarction patients and control samples. Ficolin (collagen/fibrinogen domain containing) 1 (FCN1), CD14 molecule (CD14), S100 calcium binding protein A9 (S100A9), and mitochondrial aldehyde dehydrogenase 2 (ALDH2) were identified as critical target molecules; hsa-let-7d, hsa-let-7b, hsa-miR-124-3, and hsa-miR-9-1 were identified as potential regulators of the expression of the key genes in the two biggest modules. Conclusions. FCN1, CD14, S100A9, ALDH2, hsa-let-7d, hsa-let-7b, hsa-miR-124-3, and hsa-miR-9-1 were identified as potential candidate regulators in acute myocardial infarction. These findings might provide new comprehension into the underlying molecular mechanism of disease.


2021 ◽  
Author(s):  
Yuxuan HUANG ◽  
Ge CUI

Abstract Aims: To utilize the bioinformatics to analyze the differentially expressed genes (DEGs), interaction proteins, perform gene enrichment analysis, protein-protein interaction network (PPI) and map the hub genes between colorectal cancer(CRC) and colorectal adenocarcinomas(CA).Methods: We analyzed a microarray dataset (GSE32323 and GSE4183) from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in tumor tissues and non-cancerous tissues were identified using the dplyr and Venn diagram packages of the R Studio software. Functional annotation of the DEGs was performed using the Gene Ontology (GO) website. Pathway enrichment (KEGG) used the WebGestalt to analyze the data and R Studio to generate the graph. We constructed a protein–protein interaction (PPI) network of DEGs using STRING and Cytoscape software was used for visualization. Survival analysis of the hub genes and was performed using the online platform GEPIA to determine the prognostic value of the expression of hub genes in cell lines from CRC patients. The expression of molecules with prognostic values was validated on the UALCAN database. The expression of hub genes was examined using the Human Protein Atlas. Results: Applying the GEO2R analysis and R studio, we identified a total of 471 upregulated and 278 downregulated DEGs. By using the online database WebGestalt, we identified the most relevant biological networks involving DEGs with statistically significant differences in expression were mainly associated with biological processes involved in the cell proliferation, cell cycle transition, cell homeostasis and indicated the role of each DEGs in cell cycle regulation pathways. We found 10 hub genes with prognostic values were overexpressed in the CRC and CA samples.Conclusion: we found out ten hub genes and three core genes closely associated with the pathogenesis and prognosis of CRC and CA, which is of great significance for colorectal tumor early detection and prognosis evaluation.


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