Abstract
Chronic obstructive pulmonary disease (COPD) was classified by the Centers for Disease Control and Prevention in 2014 as the 3rd leading cause of death in the United States (US). The main cause of COPD is exposure to tobacco smoke and air pollutants. Problems associated with COPD include under-diagnosis of the disease and an increase in the number of smokers worldwide. The goal of our study is to identify disease variability in the gene expression profiles of COPD subjects compared to controls, by reanalyzing pre-existing, publicly available microarray expression datasets. Our inclusion criteria for microarray datasets selected for smoking status, age and sex of blood donors reported. Our datasets used Affymetrix, Agilent microarray platforms (7 datasets, 1,262 samples). We re-analyzed the curated raw microarray expression data using R packages, and used Box-Cox power transformations to normalize datasets. To identify significant differentially expressed genes we used generalized least squares models with disease state, age, sex, smoking status and study as effects that also included binary interactions, followed by likelihood ratio tests (LRT). We found 3,315 statistically significant (Storey-adjusted q-value <0.05) differentially expressed genes with respect to disease state (COPD or control). We further filtered these genes for biological effect using results from LRT q-value <0.05 and model estimates’ 10% two-tailed quantiles of mean differences between COPD and control), to identify 679 genes. Through analysis of disease, sex, age, and also smoking status and disease interactions we identified differentially expressed genes involved in a variety of immune responses and cell processes in COPD. We also trained a logistic regression model using the common array genes as features, which enabled prediction of disease status with 81.7% accuracy. Our results give potential for improving the diagnosis of COPD through blood and highlight novel gene expression disease signatures.
Highlights
Chronic obstructive pulmonary disease (COPD) impairs lung function and reduces lung capacity
The goal of our study is to identify disease variability in the gene expression profiles of COPD subjects compared to controls, by reanalyzing pre-existing, publicly available microarray expression datasets
Our study is the largest reanalysis of public microarray datasets on blood expression for COPD to date, to the best of our knowledge, and our results offer prospective gene and pathway associations that may be targeted for improving COPD diagnosis and treatment
Summary
Chronic obstructive pulmonary disease (COPD) impairs lung function and reduces lung capacity. In COPD there is inflammation of the bronchial tubes (chronic bronchitis) [1] and destruction of the air sacs (emphysema) [2] within the lungs [3,4,5,6]. Chronic bronchitis and emphysema often occur together and are grouped under COPD [1, 2]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) describes COPD as a common and preventable disease that is caused by exposure to harmful particles and gases that affect the airways and alveolar of the lungs [7, 8]. COPD progresses with time and the damage caused to the lungs is irreversible [8, 9], and we do not currently have adequate therapies to control COPD progression
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