DEVELOPING MULTI-OMICS ANALYSIS PIPELINE TO IDENTIFY NOVEL DRUG REPURPOSING TARGETS FOR COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by breathlessness due to airflow obstruction. COPD is the third leading cause of death worldwide. So far, none of the existing pharmacological treatments for COPD can stop the progressive decline in lung function. Drug repurposing is the application of existing approved therapeutic compounds for new disease indications, which may reduce the cost and time of new drug development. So far, there is not any systematic multi-omics data integration for drug repurposing in COPD. The goal of this project is to develop a systems biology pipeline for the identification of biological-relevant gene targets with drug repurposing potential for COPD treatment using multi-omics integration. Here we implemented a computational methodology to identify drug repurposing targets for COPD. We integrated multi-omics COPD data including, genome, transcriptome, proteome, metabolome, interactome data, and drug-target information. A distance-based network model was created to rank the potential candidate genes. Fifty genes were prioritized as COPD signature genes for their overall proximity to signature genes identified at all omics levels. Forty of them may be considered as “druggable” targets. Literature search reported CRCX4 – Plerixafor as one prioritized targets-gene pair for drug repurposing. The bone marrow stimulant Plerixafor is currently being evaluated for COPD treatment in clinical trials, suggesting that our pipeline is finding promising drug repurposing targets. Our work, for the first time, applied a systematic approach integrating multiple omics data to find drug repurposing targets for COPD.