Integrative bioinformatics approaches to identify novel molecular gene expression signatures and pathways of Cystic Fibrosis (CF)

Abstract

Cystic Fibrosis (CF) is the most common lethal autosomal recessive disorder characterized by the defective function of the CF transmembrane conductance regulator (CFTR) gene. Worldwide, the incidence ratio of CF is approximately 1:3000 in live births per annum. Recently, the number of adult patients has been reported to outnumber the number of pediatric sufferers. Though the diagnosis and treatment are available for CF patients’ corrective treatment for non-specific mutations, patients with rare mutations, advances in personalized biomarkers, and whether other genes and signaling pathways are related to CF are being investigated and they are also in the early stage of development and validation. In the present study, we have employed systems biology approaches to retrieve the potential biomarkers and pathways from transcriptomic profiling. Initially, we identified 104 up-regulated and 107 down-regulated genes from a total of 54676 differentially expressed genes. The up-regulatory genes mainly concentrate on Glutamatergic synapses, and the down-regulatory genes are on Ubiquitin mediated proteolysis. The involved pathways associated with these genes were also assessed through pathway enrichment, and we mainly focused on different pathways related to bronchial epithelial cells. After the subsequent enrichment of these genes, we have identified 6 hub genes, WWP2; RNASEL; CUL1; CDC42; HDAC4, and UBA2, which play a crucial role in CF and are verified by expression profile analysis. Our study found that the WWP2 gene in CF, as reported here for the first time.