Network analysis of gene expression in peripheral blood identifies mTOR and NF-κB pathways involved in antipsychotic-induced extrapyramidal symptoms

AbstractBackgroundDiet may alter gene expression in immune cells involved in cardio-metabolic disease susceptibility. However, we still lack a robust understanding of the association between diet and immune cell-related gene expression in humans.ObjectiveOur objective was to examine the associations between dietary patterns (DPs) and gene expression profiles in peripheral blood mononuclear cells (PBMCs) in a population of healthy, Norwegian adults.MethodsWe used factor analysis to define a posteriori DPs from food frequency questionnaire-based dietary assessment data. In addition, we derived interpretable features from microarray-based gene expression data (13 967 transcripts) using two algorithms: CIBERSORT for estimation of cell subtype proportions, and weighted gene co-expression network analysis (WGCNA) for cluster discovery. Finally, we associated DPs with either CIBERSORT-predicted PBMC leukocyte distribution or WGCNA gene clusters using linear regression models. All analyses were gender-stratified (n = 130 women and 105 men).ResultsWe detected three DPs that broadly reflected Western, Vegetarian, and Low carbohydrate diets. CIBERSORT-predicted percentage of monocytes associated strongly and negatively with the Vegetarian DP in both women and men. For women, the Vegetarian DP associated most strongly with a large gene cluster consisting of 600 genes mainly involved in regulation of DNA transcription. For men, the Western DP inversely associated most strongly with a smaller cluster of 36 genes mainly involved in regulation of metabolic and inflammatory processes. In subsequent protein-protein interaction network analysis, the most important driver genes within these WGCNA gene clusters seemed to physically interact in biological networks.ConclusionsDPs may affect percentage monocytes and regulation of key biological processes within the PBMC pool. Although the present findings are exploratory, our analysis pipeline serves a useful framework for studying the association between diet and gene expression.

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Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms

The Pharmacogenomics Journal ◽

10.1038/tpj.2015.48 ◽

2015 ◽

Vol 16 (3) ◽

pp. 293-300 ◽

Cited By ~ 3

Author(s):

S Mas ◽

P Gassó ◽

D Boloc ◽

N Rodriguez ◽

F Mármol ◽

...

Keyword(s):

Gene Expression ◽

Network Analysis ◽

Mtor Pathway ◽

Extrapyramidal Symptoms ◽

New Evidence

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Gene expression profiling and network analysis of peripheral blood monocytes in a chronic model of allergic asthma

Microbiology and Immunology ◽

10.1111/j.1348-0421.2010.00242.x ◽

2010 ◽

Vol 54 (9) ◽

pp. 558-563 ◽

Cited By ~ 4

Author(s):

Glenn P. Dorsam ◽

Scott A. Hoselton ◽

Ashley R. Sandy ◽

Amali E. Samarasinghe ◽

Emilie E. Vomhof-DeKrey ◽

...

Keyword(s):

Gene Expression ◽

Network Analysis ◽

Gene Expression Profiling ◽

Allergic Asthma ◽

Peripheral Blood ◽

Expression Profiling ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Chronic Model

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Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis

Thorax ◽

10.1136/thoraxjnl-2018-211929 ◽

2018 ◽

Vol 74 (2) ◽

pp. 132-140 ◽

Cited By ~ 17

Author(s):

John E McDonough ◽

Naftali Kaminski ◽

Bernard Thienpont ◽

James C Hogg ◽

Bart M Vanaudenaerde ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Network Analysis ◽

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Peripheral Blood ◽

Underlying Disease ◽

Forced Expiratory Volume ◽

Correlation Network

BackgroundIdiopathic pulmonary fibrosis (IPF) is a severe lung disease characterised by extensive pathological changes. The objective for this study was to identify the gene network and regulators underlying disease pathology in IPF and its association with lung function.MethodsLung Tissue Research Consortium dataset with 262 IPF and control subjects (GSE47460) was randomly divided into two non-overlapping groups for cross-validated differential gene expression analysis. Consensus weighted gene coexpression network analysis identified overlapping coexpressed gene modules between both IPF groups. Modules were correlated with lung function (diffusion capacity, DLCO; forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC) and enrichment analyses used to identify biological function and transcription factors. Module correlation with miRNA data (GSE72967) identified associated regulators. Clinical relevance in IPF was assessed in a peripheral blood gene expression dataset (GSE93606) to identify modules related to survival.ResultsCorrelation network analysis identified 16 modules in IPF. Upregulated modules were associated with cilia, DNA replication and repair, contractile fibres, B-cell and unfolded protein response, and extracellular matrix. Downregulated modules were associated with blood vessels, T-cell and interferon responses, leucocyte activation and degranulation, surfactant metabolism, and cellular metabolic and catabolic processes. Lung function correlated with nine modules (eight with DLCO, five with FVC). Intermodular network of transcription factors and miRNA showed clustering of fibrosis, immune response and contractile modules. The cilia-associated module was able to predict survival (p=0.0097) in an independent peripheral blood IPF cohort.ConclusionsWe identified a correlation gene expression network with associated regulators in IPF that provides novel insight into the pathological process of this disease.

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