A translational framework of genoproteomic studies for cardiovascular drug discovery

Abstract

Cardiovascular drug development has faced significant challenges in recent decades. The emergence of population-scale genome- and proteome-wide data, alongside sophisticated genetic analytical tools like Mendelian randomization and pragmatic target trials, presents an unprecedented chance to identify and validate drug-targeting proteins for cardiovascular disease. However, how to translate these advances into clinical applications remains to be discovered. This study proposes and validates a translational framework that leverages emerging genoproteomic data and cutting-edge causal analysis techniques to address the intricate benefit-risk concerns associated with cardiovascular drug development. Specifically, the framework elucidates underlying biological mechanisms, identifies and validates potential drug-targeting proteins, and explores the unintended side effects, complementary with pragmatic target trials. Moreover, we illustrate the translational framework via a step-by-step example alongside practical implementation recommendations for cardiovascular drug discovery. We envision this translational framework as a starting point in advancing multi-omics studies, thereby accelerating cardiovascular drug development.