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

9 Citations (Scopus)

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

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Metabolomics
Chronic Obstructive Pulmonary Disease
Emphysema
Glycerophospholipids
Phenotype
Lung
Sphingolipids
Oxidative Phosphorylation
Antigen Presentation
T-Cell Antigen Receptor
Proline
Liquid Chromatography
Arginine
Disease Progression
Digestion
Blood Cells
Mass Spectrometry
Hospitalization
Fats

ASJC Scopus subject areas

  • General

Cite this

Cruickshank-Quinn, C. I., Jacobson, S., Hughes, G., Powell, R. L., Petrache, I., Kechris, K., ... Reisdorph, N. (2018). Metabolomics and transcriptomics pathway approach reveals outcome-specific perturbations in COPD. Scientific Reports, 8(1), [17132]. https://doi.org/10.1038/s41598-018-35372-w

Metabolomics and transcriptomics pathway approach reveals outcome-specific perturbations in COPD. / Cruickshank-Quinn, Charmion I.; Jacobson, Sean; Hughes, Grant; Powell, Roger L.; Petrache, Irina; Kechris, Katerina; Bowler, Russell; Reisdorph, Nichole.

In: Scientific Reports, Vol. 8, No. 1, 17132, 01.12.2018.

Research output: Contribution to journalArticle

Cruickshank-Quinn, CI, Jacobson, S, Hughes, G, Powell, RL, Petrache, I, Kechris, K, Bowler, R & Reisdorph, N 2018, 'Metabolomics and transcriptomics pathway approach reveals outcome-specific perturbations in COPD', Scientific Reports, vol. 8, no. 1, 17132. https://doi.org/10.1038/s41598-018-35372-w
Cruickshank-Quinn, Charmion I. ; Jacobson, Sean ; Hughes, Grant ; Powell, Roger L. ; Petrache, Irina ; Kechris, Katerina ; Bowler, Russell ; Reisdorph, Nichole. / Metabolomics and transcriptomics pathway approach reveals outcome-specific perturbations in COPD. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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