Differential Connectivity Of MicroRNA/mRNA Association Networks Reveals Bronchial MicroRNAs Associated With Chronic Obstructive Pulmonary Disease

We hypothesize that bronchial epithelium microRNAs (miRNAs) regulate airway gene expression and may be used to better understand the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). We propose a novel approach to identify miRNAs functionally associated with disease by computing the differential connectivity (DC) of miRNA/mRNA association networks between disease and normal states. By measuring the change in the structure of the miRNA/mRNA disease specific networks we may identify microRNAs which regulate genes that contribute to the disease. We integrate miRNA expression via small RNA sequencing and gene expression data from 182 subjects (129 COPD cases/53 controls). In the differential connectivity (DC) method, each miRNA is assigned a DC score, which captures the overall difference in the pairwise microRNA-gene correlation strengths between case and control …