Beyond the network-based multi-omics data integration in COPD: a pathway-centric analysis

Chronic obstructive pulmonary disease (COPD) is a lung disease causing hundred thousand of death each year worldwide and defined as a respiratory and airflow impairment majorly due to large and small airways dysfunctions. COPD could be considered as a syndrome that includes disease axes of variable pathological and clinical conditions. Despite recent advances, the comprehension of the molecular mechanisms responsible for COPD disease spectrum is far to be reached. Moreover, we should also consider continuous smoking exposure, which could lead to variability in the disease mechanisms and progression. Network-based multi-omics data integration can help to study the association between molecular determinants on diverse biomolecular layers in a disease context. In a previous study, we leveraged lung RNA-seq and DNA-methylation data of a COPD-control cohort to build a correlation-based integrated network (called coupled network), that helped to unveil genes involved in immune and inflammatory modulation of COPD. Therefore, in our previous study we highlighted the most important genes of the coupled network and inspected their single contribution to diseaserelated pathways. In this study we aim to overcome this limitation by performing a pathway activity analysis by considering the expression and DNA methylation profiles of coupled network genes. Moreover, we exploit this analysis to study the possible contribution of coupled network genes to the differential disease progression between current and former smokers patients.