Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease.

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-diagn...

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Main Authors: Lavida R K Rogers, Madison Verlinde, George I Mias
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0224750
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author Lavida R K Rogers
Madison Verlinde
George I Mias
author_facet Lavida R K Rogers
Madison Verlinde
George I Mias
author_sort Lavida R K Rogers
collection DOAJ
description 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.
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spelling doaj.art-0a239f99dbf04dadb94436dfa36dbefc2022-12-21T19:59:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011411e022475010.1371/journal.pone.0224750Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease.Lavida R K RogersMadison VerlindeGeorge I MiasChronic 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.https://doi.org/10.1371/journal.pone.0224750
spellingShingle Lavida R K Rogers
Madison Verlinde
George I Mias
Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease.
PLoS ONE
title Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease.
title_full Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease.
title_fullStr Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease.
title_full_unstemmed Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease.
title_short Gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease.
title_sort gene expression microarray public dataset reanalysis in chronic obstructive pulmonary disease
url https://doi.org/10.1371/journal.pone.0224750
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