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Key genes and co-expression modules involved in asthma pathogenesis.

ABSTRACT: Machine learning and weighted gene co-expression network analysis (WGCNA) have been widely used due to its well-known accuracy in the biological field. However, due to the nature of a gene's multiple functions, it is challenging to locate the exact genes involved in complex diseases such as asthma. In this study, we combined machine learning and WGCNA in order to analyze the gene expression data of asthma for better understanding of associated pathogenesis. Specifically, the role of machine learning is assigned to screen out the key genes in the asthma development, while the role of WGCNA is to set up gene co-expression network. Our results indicated that hormone secretion regulation, airway remodeling, and negative immune regulation, were all regulated by critical gene modules associated with pathogenesis of asthma progression. Overall, the method employed in this study helped identify key genes in asthma and their roles in the asthma pathogenesis.

SUBMITTER: Huang Y

PROVIDER: S-EPMC7003696 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Key genes and co-expression modules involved in asthma pathogenesis.

Huang Yuyi Y Liu Hui H Zuo Li L Tao Ailin A

PeerJ 20200203

Machine learning and weighted gene co-expression network analysis (WGCNA) have been widely used due to its well-known accuracy in the biological field. However, due to the nature of a gene's multiple functions, it is challenging to locate the exact genes involved in complex diseases such as asthma. In this study, we combined machine learning and WGCNA in order to analyze the gene expression data of asthma for better understanding of associated pathogenesis. Specifically, the role of machine lear ...[more]

PMID: 32117613

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Project description:Atrial fibrillation (AF) is the most common form of cardiac arrhythmia and significantly increases the risks of morbidity, mortality and health care expenditure; however, treatment for AF remains unsatisfactory due to the complicated and incompletely understood underlying mechanisms. In the present study, weighted gene co‑expression network analysis (WGCNA) was conducted to identify key modules and hub genes to determine their potential associations with AF. WGCNA was performed in an AF dataset GSE79768 obtained from the Gene Expression Omnibus, which contained data from paired left and right atria in cardiac patients with persistent AF or sinus rhythm. Differentially expressed gene (DEG) analysis was used to supplement and validate the results of WGCNA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were also performed. Green and magenta modules were identified as the most critical modules associated with AF, from which 6 hub genes, acetyl‑CoA Acetyltransferase 1, death domain‑containing protein CRADD, gypsy retrotransposon integrase 1, FTX transcript, XIST regulator, transcription elongation factor A like 2 and minichromosome maintenance complex component 3 associated protein, were hypothesized to serve key roles in the pathophysiology of AF due to their increased intramodular connectivity. Functional enrichment analysis results demonstrated that the green module was associated with energy metabolism, and the magenta module may be associated with the Hippo pathway and contain multiple interactive pathways associated with apoptosis and inflammation. In addition, the blue module was identified to be an important regulatory module in AF with a higher specificity for the left atria, the genes of which were primarily correlated with complement, coagulation and extracellular matrix formation. These results suggest that may improve understanding of the underlying mechanisms of AF, and assist in identifying biomarkers and potential therapeutic targets for treating patients with AF.

Project description:BackgroundFat deposition is an important economic trait in livestock and poultry production. However, the relationship between various genes and signal pathways of fat deposition is still unclear to a large extent. The purpose of this study is to analyze the potential molecular targets and related molecular pathways in bovine subcutaneous adipose tissue.ResultsWe downloaded the GSE116775 microarray dataset from Gene Expression Omnibus (GEO). The weighted gene co-expression network (WGCNA) was used to analyze the gene expression profile, and the key gene modules with the highest correlation with subcutaneous adipose tissue were identified, and the functional enrichment of the key modules was analyzed. Then, the "real" Hub gene was screened by in-module analysis and protein-protein interaction network (PPI), and its expression level in tissue samples and adipocytes was verified. The study showed that a total of nine co-expression modules were identified, and the number of genes in these modules ranged from 101 to 1,509. Among them, the blue module is most closely related to subcutaneous adipose tissue, containing 1,387 genes. These genes were significantly enriched in 10 gene ontologies including extracellular matrix organization, biological adhesion, and collagen metabolic process, and were mainly involved in pathways including ECM-receptor interaction, focal adhesion, cAMP signaling pathway, PI3K-AKT signaling pathway, and regulation of lipolysis in adipocytes. In the PPI network and coexpression network, five genes (CAV1, ITGA5, COL5A1, ABL1, and HSPG2) were identified as "real" Hub genes. Analysis of Hub gene expression by dataset revealed that the expression of these Hub genes was significantly higher in subcutaneous adipose tissue than in other tissues. In addition, real-time fluorescence quantitative PCR (qRT-PCR) analysis based on tissue samples and adipocytes also confirmed the above results.ConclusionIn this study, five key genes related to subcutaneous adipose tissue were discovered, which laid a foundation for further study of the molecular regulation mechanism of subcutaneous adipose tissue development and adipose deposition.

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Key genes and co-expression modules involved in asthma pathogenesis.

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Key genes and co-expression modules involved in asthma pathogenesis.

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