Application of Weighted Gene Co-Expression Network Analysis to Explore the Key Genes in Alzheimer’s Disease
Background: Weighted co-expression network analysis (WGCNA) is a powerful systems biology method to describe the correlation of gene expression based on the microarray database, which can be used to facilitate the discovery of therapeutic targets or candidate biomarkers in diseases. Objective: To ex...
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Published in | Journal of Alzheimer's disease Vol. 65; no. 4; pp. 1353 - 1364 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London, England
SAGE Publications
01.01.2018
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Subjects | |
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Abstract | Background:
Weighted co-expression network analysis (WGCNA) is a powerful systems biology method to describe the correlation of gene expression based on the microarray database, which can be used to facilitate the discovery of therapeutic targets or candidate biomarkers in diseases.
Objective:
To explore the key genes in the development of Alzheimer’s disease (AD) by using WGCNA.
Methods:
The whole gene expression data GSE1297 from AD and control human hippocampus was obtained from the GEO database in NCBI. Co-expressed genes were clustered into different modules. Modules of interest were identified through calculating the correlation coefficient between the module and phenotypic traits. GO and pathway enrichment analyses were conducted, and the central players (key hub genes) within the modules of interest were identified through network analysis. The expression of the identified key genes was confirmed in AD transgenic mice through using qRT-PCR.
Results:
Two modules were found to be associated with AD clinical severity, which functioning mainly in mineral absorption, NF-κB signaling, and cGMP-PKG signaling pathways. Through analysis of the two modules, we found that metallothionein (MT), Notch2, MSX1, ADD3, and RAB31 were highly correlated with AD phenotype. Increase in expression of these genes was confirmed in aged AD transgenic mice.
Conclusion:
WGCNA analysis can be used to analyze and predict the key genes in AD. MT1, MT2, MSX1, NOTCH2, ADD3, and RAB31 are identified to be the most relevant genes, which may be potential targets for AD therapy. |
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AbstractList | Weighted co-expression network analysis (WGCNA) is a powerful systems biology method to describe the correlation of gene expression based on the microarray database, which can be used to facilitate the discovery of therapeutic targets or candidate biomarkers in diseases.
To explore the key genes in the development of Alzheimer's disease (AD) by using WGCNA.
The whole gene expression data GSE1297 from AD and control human hippocampus was obtained from the GEO database in NCBI. Co-expressed genes were clustered into different modules. Modules of interest were identified through calculating the correlation coefficient between the module and phenotypic traits. GO and pathway enrichment analyses were conducted, and the central players (key hub genes) within the modules of interest were identified through network analysis. The expression of the identified key genes was confirmed in AD transgenic mice through using qRT-PCR.
Two modules were found to be associated with AD clinical severity, which functioning mainly in mineral absorption, NF-κB signaling, and cGMP-PKG signaling pathways. Through analysis of the two modules, we found that metallothionein (MT), Notch2, MSX1, ADD3, and RAB31 were highly correlated with AD phenotype. Increase in expression of these genes was confirmed in aged AD transgenic mice.
WGCNA analysis can be used to analyze and predict the key genes in AD. MT1, MT2, MSX1, NOTCH2, ADD3, and RAB31 are identified to be the most relevant genes, which may be potential targets for AD therapy. Background: Weighted co-expression network analysis (WGCNA) is a powerful systems biology method to describe the correlation of gene expression based on the microarray database, which can be used to facilitate the discovery of therapeutic targets or candidate biomarkers in diseases. Objective: To explore the key genes in the development of Alzheimer’s disease (AD) by using WGCNA. Methods: The whole gene expression data GSE1297 from AD and control human hippocampus was obtained from the GEO database in NCBI. Co-expressed genes were clustered into different modules. Modules of interest were identified through calculating the correlation coefficient between the module and phenotypic traits. GO and pathway enrichment analyses were conducted, and the central players (key hub genes) within the modules of interest were identified through network analysis. The expression of the identified key genes was confirmed in AD transgenic mice through using qRT-PCR. Results: Two modules were found to be associated with AD clinical severity, which functioning mainly in mineral absorption, NF-κB signaling, and cGMP-PKG signaling pathways. Through analysis of the two modules, we found that metallothionein (MT), Notch2, MSX1, ADD3, and RAB31 were highly correlated with AD phenotype. Increase in expression of these genes was confirmed in aged AD transgenic mice. Conclusion: WGCNA analysis can be used to analyze and predict the key genes in AD. MT1, MT2, MSX1, NOTCH2, ADD3, and RAB31 are identified to be the most relevant genes, which may be potential targets for AD therapy. |
Author | Zeng, Ji Zhang, Xiao-Lin Wang, Jing-Lin Huang, Yong Liu, Rong Fang, Zheng-Yu Liuyang, Zhen-yu Wei, Hui Liang, Jia-Wei Wang, Jian-Zhi Wang, Xiao-Chuan |
Author_xml | – sequence: 1 givenname: Jia-Wei surname: Liang fullname: Liang, Jia-Wei organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 2 givenname: Zheng-Yu surname: Fang fullname: Fang, Zheng-Yu organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 3 givenname: Yong surname: Huang fullname: Huang, Yong organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 4 givenname: Zhen-yu surname: Liuyang fullname: Liuyang, Zhen-yu organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 5 givenname: Xiao-Lin surname: Zhang fullname: Zhang, Xiao-Lin organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 6 givenname: Jing-Lin surname: Wang fullname: Wang, Jing-Lin organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 7 givenname: Hui surname: Wei fullname: Wei, Hui organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 8 givenname: Jian-Zhi surname: Wang fullname: Wang, Jian-Zhi organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 9 givenname: Xiao-Chuan surname: Wang fullname: Wang, Xiao-Chuan organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 10 givenname: Ji surname: Zeng fullname: Zeng, Ji organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science – sequence: 11 givenname: Rong surname: Liu fullname: Liu, Rong email: rong.liu@hust.edu.cn organization: The Institute for Brain Research, Collaborative Innovation Center for Brain Science |
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Keywords | RAB31 Alzheimer’s disease Notch2 neurofibrillary tangles metallothionein MSX1 ADD3 WGCNA |
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Snippet | Background:
Weighted co-expression network analysis (WGCNA) is a powerful systems biology method to describe the correlation of gene expression based on the... Weighted co-expression network analysis (WGCNA) is a powerful systems biology method to describe the correlation of gene expression based on the microarray... |
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SubjectTerms | Alzheimer Disease - genetics Calmodulin-Binding Proteins - genetics Female Gene Expression Profiling Gene Regulatory Networks Genetic Predisposition to Disease - genetics Humans Male Mental Status Schedule Metallothionein - genetics MSX1 Transcription Factor - genetics rab GTP-Binding Proteins - genetics Receptor, Notch2 - genetics RNA, Messenger - metabolism Systems Biology |
Title | Application of Weighted Gene Co-Expression Network Analysis to Explore the Key Genes in Alzheimer’s Disease |
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