Dataset Information

Identification of novel biomarkers involved in pulmonary arterial hypertension based on multiple-microarray analysis.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disorder. However, studies providing PAH-related gene expression profiles are scarce. To identify hub genes involved in PAH, we investigate two microarray data sets from gene expression omnibus (GEO). A total of 150 differentially expressed genes (DEGs) were identified by limma package. Enriched Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included mitotic nuclear division, ATPase activity, and Herpes simplex virus one infection. Ten hub genes from three significant modules were ascertained by Cytoscape (CytoHubba). Gene set enrichment analysis (GSEA) plots showed that transcription elongation factor complex was the most significantly enriched gene set positively correlated with the PAH group. At the same time, solute proton symporter activity was the most significantly enriched gene set positively correlated with the control group. Correlation analysis between hub genes suggested that SMC4, TOP2A, SMC2, KIF11, KIF23, ANLN, ARHGAP11A, SMC3, SMC6 and RAD50 may involve in the pathogenesis of PAH. Then, the miRNA-target genes regulation network was performed to unveil the underlying complex association among them. Finally, RNA extracted from monocrotaline (MCT)-induced Rat-PAH model lung artery tissues were to conduct quantitative real-time PCR (qRT-PCR) to validate these hub genes. In conclusion, our study offers new evidence for the underlying molecular mechanisms of PAH as well as attractive targets for diagnosis and treatment of PAH.

SUBMITTER: Ma Y

PROVIDER: S-EPMC7494994 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of novel biomarkers involved in pulmonary arterial hypertension based on multiple-microarray analysis.

Ma Yi Y Chen Shu-Shu SS Feng Yan-Yan YY Wang Huan-Liang HL

Bioscience reports 20200901 9

Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disorder. However, studies providing PAH-related gene expression profiles are scarce. To identify hub genes involved in PAH, we investigate two microarray data sets from gene expression omnibus (GEO). A total of 150 differentially expressed genes (DEGs) were identified by limma package. Enriched Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included mito ...[more]

PMID: 32886110

Similar Datasets

Project description:Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by vascular cell proliferation; the pathogenesis of PAH has yet to be fully elucidated. Publicly available genetic data were downloaded from the Gene Expression Omnibus (GEO) database, and gene set enrichment analysis (GSEA) was used to determine significant differences in gene expression between tissues with PAH and healthy lung tissues. Differentially expressed genes (DEGs) were identified using the online tool, GEO2R, and functional annotation of DEGs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Next, the construction and module analysis of the protein-protein interaction (PPI) network and verification of the expression level of hub genes was performed. Finally, prediction and enrichment analysis of microRNAs associated with the hub genes was carried out. A total of 110 DEGs were detected by screening PAH and healthy lung samples. The expression of nine genes [polo-like kinase 4 (PLK4), centromere protein U, kinesin family member 20B, structural maintenance of chromosome 2 (SMC2), abnormal spindle microtubule assembly, Fanconi Anemia complementation group I, kinesin family member 18A, spindle apparatus coiled-coil protein 1, and MIS18 binding protein 1] was elevated in PAH; this was statistically significant compared with their expression in healthy lung tissue, and they were identified as hub genes. GO and KEGG analysis showed that the variations in DEGs were abundant in DNA-templated transcription, sister chromatid cohesion, mitotic nuclear division, cell proliferation, and regulation of the actin cytoskeleton. In conclusion, this study has successfully identified hub genes and key pathways of PAH, with a total of 110 DEGs and nine hub genes related to PAH, especially the PLK4 and SMC2 genes, thus providing important clues for the in-depth understanding of the molecular mechanism of PAH and providing potential therapeutic targets.

Project description:BackgroundPulmonary arterial hypertension (PAH) is a devastating chronic cardiopulmonary disease without an effective therapeutic approach. The underlying molecular mechanism of PAH remains largely unexplored at single-cell resolution.MethodsSingle-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database (GSE210248) was included and analyzed comprehensively. Additionally, microarray transcriptome data including 15 lung tissue from PAH patients and 11 normal samples (GSE113439) was also obtained. Seurat R package was applied to process scRNA-seq data. Uniform manifold approximation and projection (UMAP) was utilized for dimensionality reduction and cluster identification, and the SingleR package was performed for cell annotation. FindAllMarkers analysis and ClusterProfiler package were applied to identify differentially expressed genes (DEGs) for each cluster in GSE210248 and GSE113439, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) were used for functional enrichment analysis of DEGs. Microenvironment Cell Populations counter (MCP counter) was applied to evaluate the immune cell infiltration. STRING was used to construct a protein-protein interaction (PPI) network of DEGs, followed by hub genes selection through Cytoscape software and Veen Diagram.ResultsNineteen thousand five hundred seventy-six cells from 3 donors and 21,896 cells from 3 PAH patients remained for subsequent analysis after filtration. A total of 42 cell clusters were identified through UMAP and annotated by the SingleR package. 10 cell clusters with the top 10 cell amounts were selected for consequent analysis. Compared with the control group, the proportion of adipocytes and fibroblasts was significantly reduced, while CD8+ T cells and macrophages were notably increased in the PAH group. MCP counter revealed decreased distribution of CD8+ T cells, cytotoxic lymphocytes, and NK cells, as well as increased infiltration of monocytic lineage in PAH lung samples. Among 997 DEGs in GSE113439, module 1 with 68 critical genes was screened out through the MCODE plug-in in Cytoscape software. The top 20 DEGs in each cluster of GSE210248 were filtered out by the Cytohubba plug-in using the MCC method. Eventually, WDR43 and GNL2 were found significantly increased in PAH and identified as the hub genes after overlapping these DEGs from GSE210248 and GSE113439.ConclusionWDR43 and GNL2 might provide novel insight into revealing the new molecular mechanisms and potential therapeutic targets for PAH.

Dataset Information

Identification of novel biomarkers involved in pulmonary arterial hypertension based on multiple-microarray analysis.

Publications

Identification of novel biomarkers involved in pulmonary arterial hypertension based on multiple-microarray analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets