scholarly journals Identification of biomarkers and pathogenesis in severe asthma by coexpression network analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zeyi Zhang ◽  
Jingjing Wang ◽  
Ou Chen
Keyword(s):  
Network Analysis ◽  
Severe Asthma ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Asthma Severity ◽  
Functional Enrichment ◽  
Coexpression Network ◽  
Validation Dataset ◽  
Hub Genes ◽  
Coexpression Network Analysis

Abstract Background Severe asthma is a heterogeneous inflammatory disease. The increase in precise immunotherapy for severe asthmatics requires a greater understanding of molecular mechanisms and biomarkers. In this study, we aimed to identify the underlying mechanisms and hub genes that determine asthma severity. Methods Differentially expressed genes (DEGs) were identified based on bronchial epithelial brushings from mild and severe asthmatics. Then, weighted gene coexpression network analysis (WGCNA) was used to identify gene networks and the module most significantly associated with asthma severity. Furthermore, hub gene screening and functional enrichment analysis were performed. Replication with another dataset was conducted to validate the hub genes. Results DEGs from 14 mild and 11 severe asthmatics were subjected to WGCNA. Six modules associated with asthma severity were identified. Three modules were positively correlated (P < 0.001) with asthma severity and contained genes that were upregulated in severe asthmatics. Functional enrichment analysis showed that genes in the most significant module were mainly enriched in neutrophil activation and degranulation, and cytokine receptor interaction. Hub genes included CXCR1, CXCR2, CCR1, CCR7, TLR2, FPR1, FCGR3B, FCGR2A, ITGAM, and PLEK; CXCR1, CXCR2, and TLR2 were significantly related to asthma severity in the validation dataset. The combination of ten hub genes exhibited a moderate ability to distinguish between severe and mild-moderate asthmatics. Conclusion Our results identified biomarkers and characterized potential pathogenesis of severe asthma, providing insight into treatment targets and prognostic markers.

scholarly journals Identification of Biomarkers and Pathogenesis in Severe Asthma by Co-expression Network Analysis

2020 ◽  
Author(s):  
Zeyi Zhang ◽  
Ou Chen ◽  
Jingjing Wang
Keyword(s):  
Network Analysis ◽  
Severe Asthma ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Area Under The Curve ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Asthma Severity ◽  
Functional Enrichment ◽  
Hub Genes

Abstract BackgroundSevere asthma is a heterogeneous inflammatory disease. The rise of precise immunotherapy for severe asthmatics underlines more understanding of molecular mechanisms and biomarkers. In this study, we aim to identify underlying mechanisms and hub genes that define asthma severity.MethodsDifferentially expressed genes were screened out based on bronchial epithelial brushings from mild and severe asthmatics. Then, the weighted gene co-expression network analysis was adopted to identify gene networks and the most significant module associated with asthma severity. Meanwhile, hub genes screening and functional enrichment analysis was performed. Receiver operating characteristic was conducted to validate the hub genes.ResultsWeighted gene co-expression network analysis identified 6 modules associated with asthma severity. Three modules were positively correlated (P < 0.001) with asthma severity, containing genes upregulated in severe asthmatics. Functional enrichment analysis found genes in the highlighted module mainly enriched in neutrophil degranulation and activation, leukocyte migration and chemotaxis. Hub genes identified in the module were CXCR1, CXCR2, CCR1, CCR7, TLR2, FPR1, FCGR3B, FCGR2A, ITGAM, and PLEK. Combining these hub genes possessed a moderate ability for discriminating between severe asthmatics and mild-moderate asthmatics with an area under the curve of 0.75.ConclusionOur results identified biomarkers and potential pathogenesis of severe asthma, which provides sight into treatment targets and prognostic markers.

scholarly journals Weighted Gene Correlation Network Analysis Identifies Specific Functional Modules and Genes in Esophageal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Wei Xu ◽  
Jian Xu ◽  
Zhiqiang Wang ◽  
Yuequan Jiang
Keyword(s):  
Esophageal Cancer ◽  
Network Analysis ◽  
Cell Cycle Progression ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Future Research ◽  
Hub Genes ◽  
Pathological Staging

Objective. Esophageal cancer (ESCA) is one of the most aggressive malignancies globally with an undesirable five-year survival rate. Here, this study was conducted for determining specific functional genes linked with ESCA initiation and progression. Methods. Gene expression profiling of ESCA was curated from TCGA (containing 160 ESCA and 11 nontumor specimens) and GSE38129 (30 paired ESCA and nontumor tissues) datasets. Differential expression analysis was conducted between ESCA and nontumor tissues with adjusted p value <0.05 and |log2fold-change|>1. Weighted gene coexpression network analysis (WGCNA) was conducted for determining the ESCA-specific coexpression modules and genes. Thereafter, ESCA-specific differentially expressed genes (DEGs) were intersected. Functional enrichment analysis was then presented with clusterProfiler package. Protein-protein interaction was conducted, and hub genes were determined. Association of hub genes with pathological staging was evaluated, and survival analysis was presented among ESCA patients. Results. This study determined 91 ESCA-specific DEGs following intersection of DEGs and ESCA-specific genes in TCGA and GSE38129 datasets. They were remarkably linked to cell cycle progression and carcinogenic pathways like the p53 signaling pathway, cellular senescence, and apoptosis. Ten ESCA-specific hub genes were determined, containing ASPM, BUB1B, CCNA2, CDC20, CDK1, DLGAP5, KIF11, KIF20 A, TOP2A, and TPX2. They were prominently associated with pathological staging. Among them, KIF11 upregulation was in relation to undesirable prognosis of ESCA patients. Conclusion. Collectively, we determined ESCA-specific coexpression modules and hub genes, which offered the foundation for future research concerning the mechanistic basis of ESCA.

scholarly journals Application of Weighted Gene Coexpression Network Analysis to Identify Key Modules and Hub Genes in Systemic Juvenile Idiopathic Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Mi Zhou ◽  
Ruru Guo ◽  
Yong-Fei Wang ◽  
Wanling Yang ◽  
Rongxiu Li ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Network Analysis ◽  
Immune Responses ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Functional Enrichment ◽  
Coexpression Network ◽  
Gene Coexpression Network ◽  
Hub Genes ◽  
Gene Coexpression ◽  
Coexpression Network Analysis

Systemic juvenile idiopathic arthritis (sJIA) is a severe autoinflammatory disorder with a still not clearly defined molecular mechanism. To better understand the disease, we used scattered datasets from public domains and performed a weighted gene coexpression network analysis (WGCNA) to identify key modules and hub genes underlying sJIA pathogenesis. Two gene expression datasets, GSE7753 and GSE13501, were used to construct the WGCNA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to the genes and hub genes in the sJIA modules. Cytoscape was used to screen and visualize the hub genes. We further compared the hub genes with the genome-wide association study (GWAS) genes and used a consensus WGCNA to verify that our conclusions were conservative and reproducible across multiple independent datasets. A total of 5,414 genes were obtained for WGCNA, from which highly correlated genes were divided into 17 modules. The red module demonstrated the highest correlation with the sJIA module ( r = 0.8 , p = 3 e − 29 ), whereas the green-yellow module was found to be closely related to the non-sJIA module ( r = 0.62 , p = 1 e − 14 ). Functional enrichment analysis demonstrated that the red module was mostly enriched in the activation of immune responses, infection, nucleosomes, and erythrocytes, and the green-yellow module was mostly enriched in immune responses and inflammation. Additionally, the hub genes in the red module were highly enriched in erythrocyte differentiation, including ALAS2, AHSP, TRIM10, TRIM58, and KLF1. The hub genes from the green-yellow module were mainly associated with immune responses, as exemplified by the genes KLRB1, KLRF1, CD160, and KIRs. We identified sJIA-related modules and several hub genes that might be associated with the development of sJIA. Particularly, the modules may help understand the mechanisms of sJIA, and the hub genes may become biomarkers and therapeutic targets of sJIA in the future.

scholarly journals Detecting Hub Genes Associated With Lauren Subtype of Gastric Cancer by Weighted Gene Co-Expression Network Analysis

2020 ◽  
Author(s):  
XU LIU ◽  
Li Yao ◽  
Jingkun Qu ◽  
Lin Liu ◽  
XU LIU ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Network Analysis ◽  
Cancer Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Diffuse Gastric Cancer ◽  
Hub Genes ◽  
Gene Modules

Abstract Background Gastric cancer is a rather heterogeneous type of malignant tumor. Among the several classification system, Lauren classification can reflect biological and pathological differences of different gastric cancer.Method to provide systematic biological perspectives, we employ weighted gene co-expression network analysis to reveal transcriptomic characteristics of gastric cancer. GSE15459 and TCGA STAD dataset were downloaded. Co-expressional network was constructed and gene modules were identified. Result Two key modules blue and red were suggested to be associated with diffuse gastric cancer. Functional enrichment analysis of genes from the two modules was performed. Validating in TCGA STAD dataset, we propose 10 genes TNS1, PGM5, CPXM2, LIMS2, AOC3, CRYAB, ANGPTL1, BOC and TOP2A to be hub-genes for diffuse gastric cancer. Finally these ten genes were associated with gastric cancer survival. Conclusion More attention need to be paid and further experimental study is required to elucidate the role of these genes.

scholarly journals Identification of key gene modules and hub genes of human mantle cell lymphoma by coexpression network analysis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8843
Author(s):  
Dongmei Guo ◽  
Hongchun Wang ◽  
Li Sun ◽  
Shuang Liu ◽  
Shujing Du ◽  
...  
Keyword(s):  
Network Analysis ◽  
Cell Lymphoma ◽  
Enrichment Analysis ◽  
Coexpression Network ◽  
Gene Coexpression Network ◽  
Hub Genes ◽  
Gene Coexpression ◽  
Mantle Cell ◽  
Coexpression Network Analysis ◽  
Blue Module

Purpose Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma that is incurable with standard therapies. The use of gene expression analysis has been of interest, recently, to detect biomarkers for cancer. There is a great need for systemic coexpression network analysis of MCL and this study aims to establish a gene coexpression network to forecast key genes related to the pathogenesis and prognosis of MCL. Methods The microarray dataset GSE93291 was downloaded from the Gene Expression Omnibus database. We systematically identified coexpression modules using the weighted gene coexpression network analysis method (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were performed on the modules deemed important. The protein–protein interaction networks were constructed and visualized using Cytoscape software on the basis of the STRING website; the hub genes in the top weighted network were identified. Survival data were analyzed using the Kaplan–Meier method and were compared using the log-rank test. Results Seven coexpression modules consisting of different genes were applied to 5,000 genes in the 121 human MCL samples using WGCNA software. GO and KEGG enrichment analysis identified the blue module as one of the most important modules; the most critical pathways identified were the ribosome, oxidative phosphorylation and proteasome pathways. The hub genes in the top weighted network were regarded as real hub genes (IL2RB, CD3D, RPL26L1, POLR2K, KIF11, CDC20, CCNB1, CCNA2, PUF60, SNRNP70, AKT1 and PRPF40A). Survival analysis revealed that seven genes (KIF11, CDC20, CCNB1, CCNA2, PRPF40A, CD3D and PUF60) were associated with overall survival time (p < 0.05). Conclusions The blue module may play a vital role in the pathogenesis of MCL. Five real hub genes (KIF11, CDC20, CCNB1, CCNA2 and PUF60) were identified as potential prognostic biomarkers as well as therapeutic targets with clinical utility for MCL.

scholarly journals Identification of Genes Associated with the Metastasis of Pheochromocytoma/Paraganglioma Based on Weighted Gene Coexpression Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Qisheng Su ◽  
Qinpei Ding ◽  
Zunni Zhang ◽  
Zheng Yang ◽  
Yuling Qiu ◽  
...  
Keyword(s):  
Network Analysis ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
The Cancer Genome Atlas ◽  
Coexpression Network ◽  
Neuroendocrine Neoplasm ◽  
Gene Coexpression Network ◽  
Hub Genes ◽  
Gene Coexpression ◽  
Coexpression Network Analysis

Background. Pheochromocytoma/paraganglioma (PCPG) is a benign neuroendocrine neoplasm in most cases, but metastasis and other malignant behaviors can be observed in this tumor. The aim of this study was to identify genes associated with the metastasis of PCPG. Methods. The Cancer Genome Atlas (TCGA) expression profile data and clinical information were downloaded from the cbioportal, and the weighted gene coexpression network analysis (WGCNA) was conducted. The gene coexpression modules were extracted from the network through the WGCNA package of R software. We further extracted metastasis-related modules of PCPG. Enrichment analysis of Biological Process of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes was carried out for important modules, and survival analysis of hub genes in the modules was performed. Results. A total of 168 PCPG samples were included in this study. The weighted gene coexpression network was constructed with 5125 genes of the top 25% variance among the 20501 genes obtained from the database. We identified 11 coexpression modules, among which the salmon module was associated with the age of PCPG patients at diagnosis, metastasis, and malignancy of the tumors. Conclusion. WGCNA was performed to identify the gene coexpression modules and hub genes in the metastasis-related gene module of PCPG. The findings in this study provide a new clue for further study of the mechanisms underlying the PCPG metastasis.

scholarly journals Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Biao Yang ◽  
Shuxun Wei ◽  
Yan-Bin Ma ◽  
Sheng-Hua Chu
Keyword(s):  
Network Analysis ◽  
Biological Significance ◽  
Functional Enrichment ◽  
Coexpression Network ◽  
Gene Coexpression Network ◽  
Hub Genes ◽  
Gene Coexpression ◽  
Primary Intracranial Tumor ◽  
Coexpression Network Analysis ◽  
Potential Biomarkers

Meningiomas are the most common primary intracranial tumor in adults. However, to date, systemic coexpression analyses for meningiomas fail to explain its pathogenesis. The aim of the present study was to construct coexpression modules and identify potential biomarkers associated with meningioma progression. Weighted gene coexpression network analysis (WGCNA) was performed based on GSE43290, and module preservation was tested by GSE74385. Functional annotations were performed to analyze biological significance. Hub genes were selected for efficacy evaluations and correlation analyses using two independent cohorts. A total of 14 coexpression modules were identified, and module lightcyan was significantly associated with WHO grades. Functional enrichment analyses of module lightcyan were associated with tumor pathogenesis. The top 10 hub genes were extracted. Ten biomarkers, particularly AHCYL2, FGL2, and KCNMA1, were significantly related to grades and prognosis of meningioma. These findings not only construct coexpression modules leading to the better understanding of its pathogenesis but also provide potential biomarkers that represent specific on tumor grades and identify recurrence, predicting prognosis and progression of meningiomas.

scholarly journals Hub genes of stroke identified by weighted gene co-expression network analysis

2019 ◽  
Author(s):  
Junhong Li ◽  
Yang Zhai ◽  
Peng Wu ◽  
Yueqiang Hu ◽  
Wei Chen ◽  
...  
Keyword(s):  
Network Analysis ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Neuron Death ◽  
Roc Curve Analysis ◽  
Precise Diagnosis

Abstract Background Microarray-based gene expression profiling has been widely used in biomedical research. Weighted gene co-expression network analysis (WGCNA) can link microarray data directly to clinical traits and to identify rules for predicting pathological stage and prognosis of disease, it has been found useful in many biological processes. Stroke is one of the most common diseases worldwide, yet molecular mechanisms of its pathogenesis are largely unknown. We aimed to construct gene co-expression networks to identify key modules and hub genes associated with the pathogenesis of stroke.Results In this study, we screened out the differentially expressed genes from gene microarray expression profiles, then constructed the free-scale gene co-expression networks to explore the associations between gene sets and clinical features, and to identify key modules and hub genes. Subsequently, functional enrichment and the receiver operating characteristic (ROC) curve analysis were performed. And the results show that a total of 11,747 most variant genes were used for co-expression network construction. Pink and yellow modules were found to be the most significantly related to stroke. Functional enrichment analysis showed that the pink module was mainly involved in regulation of neuron regeneration, and the repair of DNA damage, while the yellow module was mainly enriched in ion transport system dysfunction which were correlated with neuron death. A total of 8 hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) were identified and validated at transcriptional levels (other datasets) and by existing literatures.Conclusions Eight hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of stroke in the future.

scholarly journals Application of Weighted Gene Co-expression Network Analysis to Identify Key Modules and Hub Genes in Systemic Juvenile Idiopathic Arthritis

2021 ◽  
Author(s):  
Mi Zhou ◽  
Ruru Guo ◽  
Yongfei Wang ◽  
Wanling Yang ◽  
Rongxiu Li ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Network Analysis ◽  
Immune Responses ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Data Sets ◽  
Hub Genes ◽  
Highly Correlated

Abstract Background: Systemic juvenile idiopathic arthritis (sJIA) is a severe autoinflammatory disorder whose molecular mechanism is still not clearly defined. To better understand the disease using scattered datasets from public domains, we performed a weighted gene co-expression network analysis (WGCNA) to identify key modules and hub genes underlying sJIA pathogenesis.Methods: Two gene expression datasets, GSE7753 and GSE13501, were used to construct WGCNA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to the entirety of genes and the hub genes in the sJIA modules. Cytoscape was used to screen and visualize the hub genes. We further compared the hub genes with the GWAS genes and used a consensus WGCNA analysis to prove that our conclusions are conservative and reproducible across multiple independent data sets. Results: A total of 5414 genes were obtained for WGCNA, from which highly correlated genes were divided into 17 modules. The red module demonstrated the highest correlation with the sJIA module (r =0.8, p=3e−29), while the green-yellow module was found to be closely related to the non-sJIA module (r =0.62, p=1e−14). Functional enrichment analysis demonstrated that the red module was largely enriched in activation of immune responses, infection, nucleosome and erythrocyte, the green-yellow module was mostly enriched in immune responses and inflammation. Additionally, the hub genes in the red module were highly enriched in erythrocyte differentiation, including ALAS2, AHSP, TRIM10, TRIM58 and KLF1. The hub genes from the green-yellow module were mainly associated with immune responses, exemplified by genes such as KLRB1, KLRF1, CD160, KIRs etc.Conclusion: We identified sJIA-related modules and several hub genes that might be associated with the development of sJIA. The two modules may help understand the mechanisms of sJIA and the hub genes may become biomarkers and therapeutic targets of sJIA in the future.

scholarly journals Identification of Key Modules and Hub Genes in Hypertrophic Cardiomyopathy Based on Integrative Weighted Gene Co-expression Network Analysis

2021 ◽  
Author(s):  
Jun Jiang ◽  
Delong Chen ◽  
Siyuan Xie ◽  
Qichao Dong ◽  
Yi Yu ◽  
...  
Keyword(s):  
Network Analysis ◽  
Hedgehog Signaling ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Hub Genes ◽  
Remodeling Of Extracellular Matrix

Abstract BackgroundHypertrophic cardiomyopathy (HCM) is a heterogeneously inherited cardiac disorder with unclear biological pathogenesis. This study aims to identify the key modules and genes involved in the development of HCM.MethodsUsing weighted gene co-expression network analysis (WGCNA) algorithm, we constructed integrative co-expression networks for the two large sample HCM datasets separately. After selecting clinically significant modules with the same clinical trait, functional enrichment analysis was performed to detect their common pathways. Based on the intramodular connectivity (IC), the shared hub genes were generated, validated, and further explored in gene set enrichment analysis (GSEA).ResultsThe orange and pink modules in GSE141910, the green and brown modules in GSE36961 were mostly related to HCM. Functional enrichment analysis suggested that HCM might exhibit enhanced processes including remodeling of extracellular matrix, activation of abnormal protein signaling, aggregation of calcium ion, and organization of cytoskeleton. SMOC2, COL16A1, RASL11B, TUBA3D, IL18R1 were defined as real hub genes due to their top IC values, significantly different expression levels, and excellent diagnostic performance in both datasets. Moreover, GSEA analysis demonstrated that pathways of the five hub genes were mainly involved in neuroactive ligand-receptor interaction, ECM-receptor interaction, Hedgehog signaling pathway.ConclusionOur study provides more comprehensive insights into the molecular mechanisms of HCM, identifies five hub genes as candidate biomarkers for HCM, which might be theoretically feasible for targeted therapy against HCM.

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