Identification of key genes and crucial modules associated with coronary artery disease by bioinformatics analysis

Abstract

The aim of this study was to identify key genes associated with coronary artery disease (CAD) and to explore the related signaling pathways. Gene expression profiles of 110 CAD and 112 non-CAD, healthy patients [CAD index (CADi) >23 and =0, respectively] were downloaded from the Gene Expression Omnibus (GEO) database (accession: GSE12288). The differentially expressed genes (DEGs) in CAD were identified using t-tests, and protein-protein interaction (PPI) networks for these DEGs were constructed using the Search Tool for the Retrieval of InteractiNg Genes (STRING) database. The Database for Annotation, Visualization and Integrated Discovery (DAVID) tool was used to identify potentially enriched biological processes (BP) among the DEGs using Gene Ontology (GO) terms, and to identify the related pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. In addition, expression-activated subnetworks (crucial modules) of the constructed PPI networks were identified using the jActiveModule plug-in, and their topological properties were analyzed using NetworkAnalyzer, both available from Cytoscape. The patient specimens were classified as grade I, II and III based on CADi values. There were 151 DEGs in grade I, 362 in grade II and 425 in grade III. In the PPI network, the gene GRB2, encoding the growth factor receptor-bound protein 2, was the only common DEG among the three grades. In addition, 10 crucial modules were identified in the PPIs, 4 of which showed significant enrichment for GO BP terms. In the 12 nodes with the highest betweenness centrality, we found two genes, encoding GRB2 and the heat shock 70 kDa protein 8 (HSPA8). Moreover, the chemokine and focal adhesion signaling pathways were selected based on their relative abundance in CAD. The GRB2 and HSPA8 proteins, as well as the chemokine and focal adhension signaling pathways, might therefore be critical for the development of CAD.

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

“…While associated with the CVDs (most significantly with CHD) and mortality, no association was detected with any of the endophenotypes, which may suggest that the effects on the CVDs are irrelevant of the pathway related to the endophenotypes under investigation. Members of the stress-inducible heat-shock protein family, including HSPA8 , are associated with the development of atherosclerosis and CHD/coronary artery disease (CAD) (Latchman, 2001 ; Mehta et al, 2005 ; He et al, 2010 ; Zhang et al, 2014 ). HSPA8 is also involved in immune response, the regulation of hematopoiesis and autophagy among the other processes (Zou et al, 2011 ; Stricher et al, 2013 ).…”

Transcriptome Signatures Reveal Candidate Key Genes in the Peripheral Blood Mononuclear Cells of Patients With Coronary Artery Disease

“…Currently, genetic and genomics related researches progress rapidly and provide new viewpoint to illuminate the molecular pathogenesis of CAD. And bioinformatics analysis also has show and devotes to search for candidate biomarkers to provide more precise screening, prompt diagnosis, sophisticated prognostic and new therapeutic targets for CAD based on massive genetic and genomics data [44]. In the present study, 1,036 DEGs were identi ed in the CAD group compared with normal control samples, including 525 up regulated genes and 511 down regulated gene.…”

Proteome and Secretome Characterization of Glioblastoma-Derived Neural Stem Cells

“…From this network, all the enriched processes from the GSEA as well as differentially expressed proteins were extracted. The resultant subnetwork was then processed with jActiveModule in order to extract a subnetwork of low adjusted p values using the simulated annealing algorithm. Direct interactions among the differentially expressed proteins and mRNAs were retrieved from MetaCore.…”