scholarly journals Identification of Hub Genes and Key Pathways Associated With Bipolar Disorder Based on Weighted Gene Co-expression Network Analysis

2019 ◽  
Vol 10 ◽  
Author(s):  
Yang Liu ◽  
Hui-Yun Gu ◽  
Jie Zhu ◽  
Yu-Ming Niu ◽  
Chao Zhang ◽  
...  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuelan Liu ◽  
Honglei Shang ◽  
Bin Li ◽  
Liyun Zhao ◽  
Ying Hua ◽  
...  

Abstract Background Despite significant progress in surgical treatment of hypoplastic left heart syndrome (HLHS), its mortality and morbidity are still high. Little is known about the molecular abnormalities of the syndrome. In this study, we aimed to probe into hub genes and key pathways in the progression of the syndrome. Methods Differentially expressed genes (DEGs) were identified in left ventricle (LV) or right ventricle (RV) tissues between HLHS and controls using the GSE77798 dataset. Then, weighted gene co-expression network analysis (WGCNA) was performed and key modules were constructed for HLHS. Based on the genes in the key modules, protein–protein interaction networks were conducted, and hub genes and key pathways were screened. Finally, the GSE23959 dataset was used to validate hub genes between HLHS and controls. Results We identified 88 and 41 DEGs in LV and RV tissues between HLHS and controls, respectively. DEGs in LV tissues of HLHS were distinctly involved in heart development, apoptotic signaling pathway and ECM receptor interaction. DEGs in RV tissues of HLHS were mainly enriched in BMP signaling pathway, regulation of cell development and regulation of blood pressure. A total of 16 co-expression network were constructed. Among them, black module (r = 0.79 and p value = 2e−04) and pink module (r = 0.84 and p value = 4e−05) had the most significant correlation with HLHS, indicating that the two modules could be the most relevant for HLHS progression. We identified five hub genes in the black module (including Fbn1, Itga8, Itga11, Itgb5 and Thbs2), and five hub genes (including Cblb, Ccl2, Edn1, Itgb3 and Map2k1) in the pink module for HLHS. Their abnormal expression was verified in the GSE23959 dataset. Conclusions Our findings revealed hub genes and key pathways for HLHS through WGCNA, which could play key roles in the molecular mechanism of HLHS.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhen-Qing Zhang ◽  
Wei-Wei Wu ◽  
Jin-Dong Chen ◽  
Guang-Yin Zhang ◽  
Jing-Yu Lin ◽  
...  

Bipolar disorder (BD) is a major and highly heritable mental illness with severe psychosocial impairment, but its etiology and pathogenesis remains unclear. This study aimed to identify the essential pathways and genes involved in BD using weighted gene coexpression network analysis (WGCNA), a bioinformatic method studying the relationships between genes and phenotypes. Using two available BD gene expression datasets (GSE5388, GSE5389), we constructed a gene coexpression network and identified modules related to BD. The analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways were performed to explore functional enrichment of the candidate modules. A protein-protein interaction (PPI) network was further constructed to identify the potential hub genes. Ten coexpression modules were identified from the top 5,000 genes in 77 samples and three modules were significantly associated with BD, which were involved in several biological processes (e.g., the actin filament-based process) and pathways (e.g., MAPK signaling). Four genes (NOTCH1, POMC, NGF, and DRD2) were identified as candidate hub genes by PPI analysis and CytoHubba. Finally, we carried out validation analyses in a separate dataset, GSE12649, and verified NOTCH1 as a hub gene and the involvement of several biological processes such as actin filament-based process and axon development. Taken together, our findings revealed several candidate pathways and genes (NOTCH1) in the pathogenesis of BD and call for further investigation for their potential research values in BD diagnosis and treatment.


2021 ◽  
Vol 15 (3) ◽  
pp. 93-100
Author(s):  
Xiang Qu ◽  
Shuang Wu ◽  
Jinggui Gao ◽  
Zhenxiu Qin ◽  
Zhenhua Zhou ◽  
...  

2020 ◽  
Author(s):  
Xuelan Liu ◽  
Honglei Shang ◽  
Bin Li ◽  
Liyun Zhao ◽  
Ying Hua ◽  
...  

Abstract Objective: Despite significant progress in surgical treatment of hypoplastic left heart syndrome (HLHS), its mortality and morbidity are still high. Little is known about the molecular abnormalities of the syndrome. In this study, we aimed to probe into hub genes and key pathways in the progression of the syndrome.Methods: Differentially expressed genes (DEGs) were identified in left ventricle (LV) or right ventricle (RV) tissues between HLHS and controls using the GSE77798 dataset. Then, weighted gene co-expression network analysis (WGCNA) was performed and key modules were constructed for HLHS. Based on the genes in the key modules, protein-protein interaction (PPI) networks were conducted, and hub genes and key pathways were screened. Finally, the GSE23959 dataset was used to validate hub genes between HLHS and controls.Results: 88 and 41 DEGs were identified for LV and RV tissues between HLHS and controls, respectively. DEGs in LV tissues of HLHS were distinctly involved in heart development, apoptotic signaling pathway and ECM receptor interaction. DEGs in RV tissues of HLHS were mainly enriched in BMP signaling pathway, regulation of cell development and regulation of blood pressure. A total of 16 co-expression network were constructed. Among them, black module (r=0.79 and p-value=2e-04) and pink module (r=0.84 and p-value=4e-05) had the most significant correlation with HLHS, indicating that the two modules could be the most relevant for HLHS progression. We identified five hub genes in the black module (including Fbn1, Itga8, Itga11, Itgb5 and Thbs2), and five hub genes (including Cblb, Ccl2, Edn1, Itgb3 and Map2k1) in the pink module for HLHS. Their abnormal expression was verified in the GSE23959 dataset. Conclusion: Our findings revealed hub genes and key pathways for HLHS through WGCNA, which could play key roles in the molecular mechanism of HLHS.


2020 ◽  
Vol 8 (21) ◽  
pp. 1348-1348
Author(s):  
Zetao Ma ◽  
Zhida Shen ◽  
Yingchao Gong ◽  
Jiaqi Zhou ◽  
Xiaoou Chen ◽  
...  

FEBS Open Bio ◽  
2021 ◽  
Author(s):  
Chun Li ◽  
Bangming Pu ◽  
Long Gu ◽  
Mingwei Zhang ◽  
Hongping Shen ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chuxiang Lei ◽  
Dan Yang ◽  
Wenlin Chen ◽  
Haoxuan Kan ◽  
Fang Xu ◽  
...  

Abstract Background Thoracic aortic aneurysm (TAA) can be life-threatening due to the progressive weakening and dilatation of the aortic wall. Once the aortic wall has ruptured, no effective pharmaceutical therapies are available. However, studies on TAA at the gene expression level are limited. Our study aimed to identify the driver genes and critical pathways of TAA through gene coexpression networks. Methods We analyzed the genetic data of TAA patients from a public database by weighted gene coexpression network analysis (WGCNA). Modules with clinical significance were identified, and the differentially expressed genes (DEGs) were intersected with the genes in these modules. Gene Ontology and pathway enrichment analyses were performed. Finally, hub genes that might be driving factors of TAA were identified. Furthermore, we evaluated the diagnostic accuracy of these genes and analyzed the composition of immune cells using the CIBERSORT algorithm. Results We identified 256 DEGs and two modules with clinical significance. The immune response, including leukocyte adhesion, mononuclear cell proliferation and T cell activation, was identified by functional enrichment analysis. CX3CR1, C3, and C3AR1 were the top 3 hub genes in the module correlated with TAA, and the areas under the curve (AUCs) by receiver operating characteristic (ROC) analysis of all the hub genes exceeded 0.7. Finally, we found that the proportions of infiltrating immune cells in TAA and normal tissues were different, especially in terms of macrophages and natural killer (NK) cells. Conclusion Chemotaxis and the complement system were identified as crucial pathways in TAA, and macrophages with interactive immune cells may regulate this pathological process.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bahman Panahi ◽  
Mohammad Amin Hejazi

AbstractDespite responses to salinity stress in Dunaliella salina, a unicellular halotolerant green alga, being subject to extensive study, but the underlying molecular mechanism remains unknown. Here, Empirical Bayes method was applied to identify the common differentially expressed genes (DEGs) between hypersaline and normal conditions. Then, using weighted gene co-expression network analysis (WGCNA), which takes advantage of a graph theoretical approach, highly correlated genes were clustered as a module. Subsequently, connectivity patterns of the identified modules in two conditions were surveyed to define preserved and non-preserved modules by combining the Zsummary and medianRank measures. Finally, common and specific hub genes in non-preserved modules were determined using Eigengene-based module connectivity or module membership (kME) measures and validation was performed by using leave-one-out cross-validation (LOOCV). In this study, the power of beta = 12 (scale-free R2 = 0.8) was selected as the soft-thresholding to ensure a scale-free network, which led to the identification of 15 co-expression modules. Results also indicate that green, blue, brown, and yellow modules are non-preserved in salinity stress conditions. Examples of enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in non-preserved modules are Sulfur metabolism, Oxidative phosphorylation, Porphyrin and chlorophyll metabolism, Vitamin B6 metabolism. Moreover, the systems biology approach was applied here, proposed some salinity specific hub genes, such as radical-induced cell death1 protein (RCD1), mitogen-activated protein kinase kinase kinase 13 (MAP3K13), long-chain acyl-CoA synthetase (ACSL), acetyl-CoA carboxylase, biotin carboxylase subunit (AccC), and fructose-bisphosphate aldolase (ALDO), for the development of metabolites accumulating strains in D. salina.


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