@article{cf45cc111086435494e4d8dad94a7c58,
title = "Network-based analysis reveals novel gene signatures in peripheral blood of patients with chronic obstructive pulmonary disease",
abstract = "Background: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death and there is a huge unmet clinical need to identify disease biomarkers in peripheral blood. Compared to gene level differential expression approaches to identify gene signatures, network analyses provide a biologically intuitive approach which leverages the co-expression patterns in the transcriptome to identify modules of co-expressed genes. Methods: A weighted gene co-expression network analysis (WGCNA) was applied to peripheral blood transcriptome from 238 COPD subjects to discover co-expressed gene modules. We then determined the relationship between these modules and forced expiratory volume in 1 s (FEV1). In a second, independent cohort of 381 subjects, we determined the preservation of these modules and their relationship with FEV1. For those modules that were significantly related to FEV1, we determined the biological processes as well as the blood cell-specific gene expression that were over-represented using additional external datasets. Results: Using WGCNA, we identified 17 modules of co-expressed genes in the discovery cohort. Three of these modules were significantly correlated with FEV1 (FDR < 0.1). In the replication cohort, these modules were highly preserved and their FEV1 associations were reproducible (P < 0.05). Two of the three modules were negatively related to FEV1 and were enriched in IL8 and IL10 pathways and correlated with neutrophil-specific gene expression. The positively related module, on the other hand, was enriched in DNA transcription and translation and was strongly correlated to CD4+, CD8+ T cell-specific gene expression. Conclusions: Network based approaches are promising tools to identify potential biomarkers for COPD. Trial registration: The ECLIPSE study was funded by GlaxoSmithKline, under ClinicalTrials.gov identifier NCT00292552and GSK No.",
keywords = "Biomarker, Blood, COPD, Co-expression, FEV, Gene expression, MRNA, Transcriptome, WGCNA",
author = "Ma'en Obeidat and Yunlong Nie and Virginia Chen and Shannon, {Casey P.} and Andiappan, {Anand Kumar} and Bernett Lee and Olaf Rotzschke and Castaldi, {Peter J.} and Hersh, {Craig P.} and Nick Fishbane and Ng, {Raymond T.} and Bruce McManus and Miller, {Bruce E.} and Stephen Rennard and Par{\'e}, {Peter D.} and Sin, {Don D.}",
note = "Funding Information: The discovery and replication populations were subsets of the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study [9]. ECLIPSE was a 3 year non-interventional, multicentre, longitudinal prospective study of COPD progression. ECLIPSE included 2164 COPD patients aged 40– 75 years (smoking history ≥10 pack-years with a post-bronchodilator FEV1/FVC < 0.70 and FEV1 < 80% predicted) and 337 smokers and 245 non-smokers who were control subjects (FEV1/FVC > 0.70 and FEV1 > 90% predicted). Blood was collected in PAXgene RNA tubes and frozen at −80 °C. The gene expression sub-study of ECLIPSE was originally designed to determine gene signatures of exacerbation in peripheral blood of patients with COPD [10]. The discovery cohort consisted of 238 former smokers with COPD. The replication cohort included 381 subjects (54.3% former and 38.6% current smokers) who were not part of the discovery set. The parent ECLIPSE study was approved by the relevant ethics review boards at each of the participating centres. Study participants provided written informed consent, and participants{\textquoteright} information was de-identified. The ECLIPSE study was funded by GlaxoSmithKline, under ClinicalTrials.gov identifier NCT00292552 and GSK No. SCO104960. This gene expression sub-study was funded by Genome British Columbia and was approved by the Providence Health Care Research Ethics Board (REB) of the University of British Columbia (UBC) (H11-00786). Funding Information: The ECLIPSE study was funded by GlaxoSmithKline, under ClinicalTrials.gov identifier NCT00292552 and GSK No. SCO104960. This gene expression sub-study was funded by Genome British Columbia. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = apr,
day = "24",
doi = "10.1186/s12931-017-0558-1",
language = "English (US)",
volume = "18",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",
number = "1",
}