Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease

• Published in: PloS one Vol. 14; no. 11; p. e0224750
• Main Authors: Rogers, Lavida R. K., Verlinde, Madison, Mias, George I.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.11.2019; Public Library of Science (PLoS)
• Subjects: Age; Age Factors; Air Pollutants - adverse effects; Air pollution; Anopheles; Artificial intelligence; Biochemistry; Bioinformatics; Biological effects; Biology and Life Sciences; Biomarkers - metabolism; Biotechnology industries; Blood; Blood donation; Blood donors; Bronchitis; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Comparative analysis; Data Mining; Datasets; Datasets as Topic; Death; Diagnosis; Disease control; DNA microarrays; Down-Regulation; Female; Gene expression; Gene Expression Profiling - statistics & numerical data; Genes; Genomes; Humans; Immune response; Inflammation; Likelihood ratio; Logistic Models; Lung diseases; Lungs; Machine Learning; Male; Medical research; Medicine and Health Sciences; Models, Genetic; Obstructive lung disease; Oligonucleotide Array Sequence Analysis - statistics & numerical data; People and Places; Physical Sciences; Pollutants; Prevention; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - etiology; Pulmonary Disease, Chronic Obstructive - genetics; Quantiles; Regression analysis; Regression models; Research and Analysis Methods; Respiratory tract diseases; Risk Assessment - methods; Risk Factors; Sex; Sex Factors; Smoke; Smokers; Smoking; Smoking - adverse effects; Smoking - epidemiology; Social Sciences; Statistical analysis; Statistical methods; Tobacco; Tobacco smoke; Transcriptome - genetics; United States - epidemiology; Up-Regulation; United States; United States > US; East Lansing Michigan; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0224750

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.