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Differential coexpression networks in bronchiolitis and emphysema phenotypes reveal heterogeneous mechanisms of chronic obstructive pulmonary disease.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with multiple molecular mechanisms. To investigate and contrast the molecular processes differing between bronchiolitis and emphysema phenotypes of COPD, we downloaded the GSE69818 microarray data set from the Gene Expression Omnibus (GEO), which based on lung tissues from 38 patients with emphysema and 32 patients with bronchiolitis. Then, weighted gene coexpression network analysis (WGCNA) and differential coexpression (DiffCoEx) analysis were performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis (KEGG) analysis. Modules and hub genes for bronchiolitis and emphysema were identified, and we found that genes in modules linked to neutrophil degranulation, Rho protein signal transduction and B cell receptor signalling were coexpressed in emphysema. DiffCoEx analysis showed that four hub genes (IFT88, CCDC103, MMP10 and Bik) were consistently expressed in emphysema patients; these hub genes were enriched, respectively, for functions of cilium assembly and movement, proteolysis and apoptotic mitochondrial changes. In our re-analysis of GSE69818, gene expression networks in relation to emphysema deepen insights into the molecular mechanism of COPD and also identify some promising therapeutic targets.

SUBMITTER: Qin J

PROVIDER: S-EPMC6787516 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Differential coexpression networks in bronchiolitis and emphysema phenotypes reveal heterogeneous mechanisms of chronic obstructive pulmonary disease.

Qin Jiangyue J Yang Ting T Zeng Ni N Wan Chun C Gao Lijuan L Li Xiaoou X Chen Lei L Shen Yongchun Y Wen Fuqiang F

Journal of cellular and molecular medicine 20190816 10

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with multiple molecular mechanisms. To investigate and contrast the molecular processes differing between bronchiolitis and emphysema phenotypes of COPD, we downloaded the GSE69818 microarray data set from the Gene Expression Omnibus (GEO), which based on lung tissues from 38 patients with emphysema and 32 patients with bronchiolitis. Then, weighted gene coexpression network analysis (WGCNA) and differential coexpression (Di ...[more]

PMID: 31419013

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Project description:Previous studies of associations of forced expiratory lung volume in one second (FEV1) with peak oxygen uptake (VO2peak) in chronic obstructive pulmonary disease (COPD) have not taken sex, age and height related variance of dynamic lung volumes into account. Nor have such demographic spread of spirometric measures been considered in studies comparing VO2peak between COPD phenotypes characterized by degree of emphysema. We aimed to assess the association of FEV1Z-score with VO2peak in COPD (n = 186) and investigate whether this association differs between emphysema (E-COPD) and non-emphysema (NE-COPD) phenotypes. Corresponding assessments using standardized percent predicted FEV1 (ppFEV1) were performed for comparison. Additionally, phenotype related differences in VO2peak were compared using FEV1Z-score and ppFEV1 as alternative expressions of FEV1. E-COPD and NE-COPD were defined by transfer factor of the lung for carbon monoxide below and above lower limits of normal (LLN), respectively. The associations were assessed in linear regression models. One unit reduction in FEV1Z-score was associated with 1.9 (95% CI 1.4, 2.5) ml/kg/min lower VO2peak. In stratified analyses, corresponding estimates were 2.2 (95% CI 1.4, 2.9) and 1.2 (95% CI 0.2, 2.2) ml/kg/min lower VO2peak in E-COPD and NE-COPD, respectively. The association did not differ statistically by COPD phenotype (p-value for interaction = 0.153). Similar estimates were obtained in analyses using standardized ppFEV1. Compared to NE-COPD, VO2peak was 2.2 (95% CI 0.8, 3.6) and 2.1 (95% CI 0.8, 3.5) ml/kg/min lower in E-COPD when adjusted for FEV1Z-score and ppFEV1, respectively. In COPD, FEV1Z-score is positively associated with VO2peak. This association was stronger in E-COPD but did not differ statistically by phenotype. Both the association of FEV1 with VO2peak and the difference in VO2peak comparing COPD phenotypes seems independent of sex, age and height related variance in FEV1. Mechanisms leading to reduction in FEV1 may contribute to lower VO2peak in E-COPD.

Project description:BackgroundThe oral and pharyngeal jaw of cichlid fishes are a classic example of evolutionary modularity as their functional decoupling boosted trophic diversification and contributed to the success of cichlid adaptive radiations. Most studies until now have focused on the functional, morphological, or genetic aspects of cichlid jaw modularity. Here we extend this concept to include transcriptional modularity by sequencing whole transcriptomes of the two jaws and comparing their gene coexpression networks.ResultsWe show that transcriptional decoupling of gene expression underlies the functional decoupling of cichlid oral and pharyngeal jaw apparatus and the two units are evolving independently in recently diverged cichlid species from Lake Tanganyika. Oral and pharyngeal jaw coexpression networks reflect the common origin of the jaw regulatory program as there is high preservation of gene coexpression modules between the two sets of jaws. However, there is substantial rewiring of genetic architecture within those modules. We define a global jaw coexpression network and highlight jaw-specific and species-specific modules within it. Furthermore, we annotate a comprehensive in silico gene regulatory network linking the Wnt and AHR signalling pathways to jaw morphogenesis and response to environmental cues, respectively. Components of these pathways are significantly differentially expressed between the oral and pharyngeal jaw apparatus.ConclusionThis study describes the concerted expression of many genes in cichlid oral and pharyngeal jaw apparatus at the onset of the independent life of cichlid fishes. Our findings suggest that - on the basis of an ancestral gill arch network-transcriptional rewiring may have driven the modular evolution of the oral and pharyngeal jaws, highlighting the evolutionary significance of gene network reuse. The gene coexpression and in silico regulatory networks presented here are intended as resource for future studies on the genetics of vertebrate jaw morphogenesis and trophic adaptation.

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Differential coexpression networks in bronchiolitis and emphysema phenotypes reveal heterogeneous mechanisms of chronic obstructive pulmonary disease.

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Differential coexpression networks in bronchiolitis and emphysema phenotypes reveal heterogeneous mechanisms of chronic obstructive pulmonary disease.

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