Identifying Protein–metabolite Networks Associated with COPD Phenotypes

Chronic obstructive pulmonary disease (COPD) is a disease in which airflow obstruction in the lung makes it difficult for patients to breathe. Although COPD occurs predominantly in smokers, there are still deficits in our understanding of the additional risk factors in smokers. To gain a deeper understanding of the COPD molecular signatures, we used Sparse Multiple Canonical Correlation Network (SmCCNet), a recently developed tool that uses sparse multiple canonical correlation analysis, to integrate proteomic and metabolomic data from the blood of 1008 participants of the COPDGene study to identify novel protein–metabolite networks associated with lung function and emphysema. Our aim was to integrate -omic data through SmCCNet to build interpretable networks that could assist in the discovery of novel biomarkers that may have been overlooked in alternative biomarker discovery methods. We found a protein–metabolite network consisting of 13 proteins and 7 metabolites which had a −0.34 correlation (p-value = 2.5 × 10(−28)) to lung function. We also found a network of 13 proteins and 10 metabolites that had a −0.27 correlation (p-value = 2.6 × 10(−17)) to percent emphysema. Protein–metabolite networks can provide additional information on the progression of COPD that complements single biomarker or single -omic analyses.