Dataset Information

Comprehensive Analysis to Identify Key Genes Involved in Advanced Atherosclerosis.

ABSTRACT:

Background

The study was aimed at finding accurate and effective therapeutic targets and deepening our understanding of the mechanisms of advanced atherosclerosis (AA).

Methods

We downloaded the gene expression datasets GSE28829, GSE120521, and GSE43292 from Gene Expression Omnibus. Weighted gene coexpression network analysis (WGCNA) was performed for GSE28829, and functional enrichment analysis and protein-protein interaction network analysis were conducted on the key module. Significant genes in the key module were analyzed by molecular complex detection, and genes in the most important subnetwork were defined as hub genes. Multiple dataset analyses for hub genes were conducted. Genes that overlapped between hub genes and differentially expressed genes (DEGs) of GSE28829 and GSE120521 were defined as key genes. Further validation for key genes was performed using GSE28829 and GSE43292. Gene set enrichment analysis (GSEA) was applied to key genes.

Results

A total of 77 significant genes in the key module of GSE28829 were screened out that were mainly associated with inflammation and immunity. The subnetwork was obtained from significant genes, and 18 genes in this module were defined as hub genes, which were related to immunity and expressed in multiple diseases, particularly systemic lupus erythematosus. Some hub genes were regulated by SPI1 and associated with the blood, spleen, and lung. After overlapping with DEGs of GSE28829 and GSE120521, a total of 10 genes (HCK, ITGAM, CTSS, TYROBP, LAPTM5, FCER1G, ITGB2, NCF2, AIF1, and CD86) were identified as key genes. All key genes were validated and evaluated successfully and were related to immune response pathways.

Conclusion

Our study suggests that the key genes related to immune and inflammatory responses are involved in the development of AA. This may deepen our understanding of the mechanisms of and provide valuable therapeutic targets for AA.

SUBMITTER: Huo TM

PROVIDER: S-EPMC8683248 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background: Bovine respiratory disease (BRD) is the most common disease in the beef and dairy cattle industry. BRD is a multifactorial disease resulting from the interaction between environmental stressors and infectious agents. However, the molecular mechanisms underlying BRD are not fully understood yet. Therefore, this study aimed to use a systems biology approach to systematically evaluate this disorder to better understand the molecular mechanisms responsible for BRD. Methods: Previously published RNA-seq data from whole blood of 18 healthy and 25 BRD samples were downloaded from the Gene Expression Omnibus (GEO) and then analyzed. Next, two distinct methods of weighted gene coexpression network analysis (WGCNA), i.e., module-trait relationships (MTRs) and module preservation (MP) analysis were used to identify significant highly correlated modules with clinical traits of BRD and non-preserved modules between healthy and BRD samples, respectively. After identifying respective modules by the two mentioned methods of WGCNA, functional enrichment analysis was performed to extract the modules that are biologically related to BRD. Gene coexpression networks based on the hub genes from the candidate modules were then integrated with protein-protein interaction (PPI) networks to identify hub-hub genes and potential transcription factors (TFs). Results: Four significant highly correlated modules with clinical traits of BRD as well as 29 non-preserved modules were identified by MTRs and MP methods, respectively. Among them, two significant highly correlated modules (identified by MTRs) and six nonpreserved modules (identified by MP) were biologically associated with immune response, pulmonary inflammation, and pathogenesis of BRD. After aggregation of gene coexpression networks based on the hub genes with PPI networks, a total of 307 hub-hub genes were identified in the eight candidate modules. Interestingly, most of these hub-hub genes were reported to play an important role in the immune response and BRD pathogenesis. Among the eight candidate modules, the turquoise (identified by MTRs) and purple (identified by MP) modules were highly biologically enriched in BRD. Moreover, STAT1, STAT2, STAT3, IRF7, and IRF9 TFs were suggested to play an important role in the immune system during BRD by regulating the coexpressed genes of these modules. Additionally, a gene set containing several hub-hub genes was identified in the eight candidate modules, such as TLR2, TLR4, IL10, SOCS3, GZMB, ANXA1, ANXA5, PTEN, SGK1, IFI6, ISG15, MX1, MX2, OAS2, IFIH1, DDX58, DHX58, RSAD2, IFI44, IFI44L, EIF2AK2, ISG20, IFIT5, IFITM3, OAS1Y, HERC5, and PRF1, which are potentially critical during infection with agents of bovine respiratory disease complex (BRDC). Conclusion: This study not only helps us to better understand the molecular mechanisms responsible for BRD but also suggested eight candidate modules along with several promising hub-hub genes as diagnosis biomarkers and therapeutic targets for BRD.

Project description:BackgroundAtherosclerosis (AS) is a chronic inflammatory disease that might induce severe cardiovascular events, such as myocardial infarction and cerebral infarction. These risk factors in the pathogenesis of AS remain uncertain and further research is needed. This study aims to explore the potential molecular mechanisms of AS by bioinformatics analyses.MethodsGSE100927 gene expression profiles, including 69 AS samples and 35 healthy controls, were downloaded from Gene Expression Omnibus database and indenfied for key genes and pathways in AS.ResultsA total of 443 differentially expressed genes (DEGs) between control and AS were identified, including 323 down-regulated genes and 120 up-regulated genes. The Gene ontology terms enriched by the up-regulated DEGs were associated with the regulation of leukocyte activation, endocytic vesicle, and cytokine binding, while the down-regulated DEGs were associated with negative regulation of cell growth, extracellular matrix, and G protein-coupled receptor binding. KEGG pathway analysis showed that the up-regulated DEGs were enriched in Osteoclast differentiation and Phagosome, while the down-regulated DEGs were enriched in vascular smooth muscle contraction and cGMP-PKG signaling pathway. Using the modular analysis of Cytoscape, we identified 3 modules mainly involved in Leishmaniasis and Osteoclast differentiation. The GSEA analysis showed the up-regulated gene sets were enriched in the ribosome, ascorbated metabolism, and propanoate metabolism. The LASSO Cox regression analysis showed the top 3 genes were TNF, CX3CR1, and COL1R1. Finally, we found these immune cells were conferred significantly higher infiltrating density in the AS group.ConclusionsOur data showed the pathway of Osteoclast differentiation and Leishmaniasis was involved in the AS process and we developed a three-gene model base on the prognosis of AS. These findings clarified the gene regulatory network of AS and may provide a novel target for AS therapy.