Metabolomics and transcriptomics pathway approach reveals outcome-specific perturbations in COPD

Charmion I. Cruickshank-Quinn, Sean Jacobson, Grant Hughes, Roger L. Powell, Irina Petrache, Katerina Kechris, Russell Bowler, Nichole Reisdorph

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Chronic obstructive pulmonary disease (COPD) comprises multiple phenotypes such as airflow obstruction, emphysema, and frequent episodes of acute worsening of respiratory symptoms, known as exacerbations. The goal of this pilot study was to test the usefulness of unbiased metabolomics and transcriptomics approaches to delineate biological pathways associated with COPD phenotypes and outcomes. Blood was collected from 149 current or former smokers with or without COPD and separated into peripheral blood mononuclear cells (PBMC) and plasma. PBMCs and plasma were analyzed using microarray and liquid chromatography mass spectrometry, respectively. Statistically significant transcripts and compounds were mapped to pathways using IMPaLA. Results showed that glycerophospholipid metabolism was associated with worse airflow obstruction and more COPD exacerbations. Sphingolipid metabolism was associated with worse lung function outcomes and exacerbation severity requiring hospitalizations. The strongest associations between a pathway and a certain COPD outcome were: fat digestion and absorption and T cell receptor signaling with lung function outcomes; antigen processing with exacerbation frequency; arginine and proline metabolism with exacerbation severity; and oxidative phosphorylation with emphysema. Overlaying transcriptomic and metabolomics datasets across pathways enabled outcome and phenotypic differences to be determined. Findings are relevant for identifying molecular targets for animal intervention studies and early intervention markers in human cohorts.

Original languageEnglish (US)
Article number17132
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • General

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