Dataset Information

Investigation of the gene co-expression network and hub genes associated with acute mountain sickness.

ABSTRACT: BACKGROUND:Acute mountain sickness has become a heavily researched topic in recent years. However, the genetic mechanism and effects have not been elucidated. Our goal is to construct a gene co-expression network to identify the key modules and hub genes associated with high altitude hypoxia. RESULTS:The GSE46480 dataset of rapidly transported healthy adults with acute mountain sickness was selected and analyzed by weighted gene co-expression network analysis (WGCNA) to construct a co-expression network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the data set were carried out using Database for Annotation Visualization and Integrated Discovery (DAVID), and the hub genes were selected. We found that the turquoise module was most significantly correlated with acute mountain sickness. The functional enrichment analysis showed that the turquoise module was related to the apoptotic process, protein transport, and translation processes. The metabolic pathway analysis identified hsa03010:ribosome and hsa04144:endocytosis as the most important pathways in the turquoise module. Ten top 10 hub genes (MRPL3, PSMC6, AIMP1, HAT1, DPY30, ATP5L, COX7B, UQCRB, DPM1, and COMMD6) for acute mountain sickness were identified. CONCLUSION:One module and 10 hub genes were identified, which were related to acute mountain sickness. The reference provided by this module may help to elucidate the mechanism of acute mountain sickness. In addition, the hub genes may be used in the future as a biomarker and therapeutic target for accurate diagnosis and treatment.

SUBMITTER: Chang Y

PROVIDER: S-EPMC7164164 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Investigation of the gene co-expression network and hub genes associated with acute mountain sickness.

Chang Yue Y He Jiange J Tang Jiqiang J Chen Kai K Wang Zhenguo Z Xia Qun Q Li Hai H

Hereditas 20200416 1

<h4>Background</h4>Acute mountain sickness has become a heavily researched topic in recent years. However, the genetic mechanism and effects have not been elucidated. Our goal is to construct a gene co-expression network to identify the key modules and hub genes associated with high altitude hypoxia.<h4>Results</h4>The GSE46480 dataset of rapidly transported healthy adults with acute mountain sickness was selected and analyzed by weighted gene co-expression network analysis (WGCNA) to construct ...[more]

PMID: 32299499

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Project description:Introduction: Acute myeloid leukemia (AML) is the most common type of leukemia in adults. However, there is a gap in understanding the molecular basis of the disease, partly because key genes associated with AML have not been extensively explored. In the current study, we aimed to identify genes that have strong association with AML based on a cross-species integrative approach. Methods: We used Weighted Gene Co-Expression Network Analysis (WGCNA) to identify co-expressed gene modules significantly correlated with human AML, and further selected the genes exhibiting a significant difference in expression between AML and healthy mouse. Protein-protein interactions, transcription factors, gene function, genetic regulation, and coding sequence variants were integrated to identify key hub genes in AML. Results: The cross-species approach identified a total of 412 genes associated with both human and mouse AML. Enrichment analysis confirmed an association of these genes with hematopoietic and immune-related functions, phenotypes, processes, and pathways. Further, the integrated analysis approach identified a set of important module genes including Nfe2, Trim27, Mef2c, Ets1, Tal1, Foxo1, and Gata1 in AML. Six of these genes (except ETS1) showed significant differential expression between human AML and healthy samples in an independent microarray dataset. All of these genes are known to be involved in immune/hematopoietic functions, and in transcriptional regulation. In addition, Nfe2, Trim27, Mef2c, and Ets1 harbor coding sequence variants, whereas Nfe2 and Trim27 are cis-regulated, making them attractive candidates for validation. Furthermore, subtype-specific analysis of the hub genes in human AML indicated high expression of NFE2 across all the subtypes (M0 through M7) and enriched expression of ETS1, LEF1, GATA1, and TAL1 in M6 and M7 subtypes. A significant correlation between methylation status and expression level was observed for most of these genes in AML patients. Conclusion: Findings from the current study highlight the importance of our cross-species approach in the identification of multiple key candidate genes in AML, which can be further studied to explore their detailed role in leukemia/AML.

Project description:ObjectiveTo investigate the differential expression gene modules and hub genes associated with Alzheimer's disease (AD) by weighted gene co-expression network analysis (WGCNA) and annotate the biological functions of these modules.MethodsWe downloaded transcriptome sequencing data from the GEO database, and according to the correlation of the genes, a gene co-expression network was constructed with the parameter setting of β=8 and a correlation coefficient threshold of 0.85. Pearson correlation test was used to calculate the correlation between the module genes and clinical traits to screen the gene modules significantly associated with AD and identify the hub genes according to the connectivity within modules. GO functional enrichment analysis and KEGG pathway analysis were used to annotate the functions of the modules. A cell model of AD was established in SH-SY5Y cells by Aβ1-42 treatment, and the mRNA expression levels of the hub genes were compared between the Aβ1-42-treated cells and the control cells.ResultsTen gene co-expression modules were constructed based on the correlations of gene expression, in which the brown (r=0.66, P < 0.001) and turquoise modules (r=-0.68, P < 0.001) were significantly correlated with the AD group. Forty-eight genes were identified as the hub genes in the co-expression network. Function annotation revealed that the genes in both modules were mainly enriched in DNA damage and repair pathways and metabolism-related pathways. Differential expression analysis of the genes revealed that the genes DNASE1, TEKT2 and MTSS1L were highly expressed while ACP2, LANCL2 and GMPR2 were lowly expressed in AD group. The results of cell experiment confirmed the up-regulation of DNASE1, TEKT2 and MTSS1L genes and the down-regulation of ACP2, LANCL2, and GMPR2 in Aβ1-42-treated SH-SY5Y cells (P < 0.01).ConclusionThe brown and turquoise modules are closely correlated with AD. The hub genes including MTSS1L, GMPR2, ACP2, ACTG1 and LANCL2 selected from the modules may participate in AD pathogenesis by regulating DNA damage and repair.

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Investigation of the gene co-expression network and hub genes associated with acute mountain sickness.

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Investigation of the gene co-expression network and hub genes associated with acute mountain sickness.

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