Comprehensive network medicine-based drug repositioning via integration of therapeutic efficacy and side effects

Despite advances in modern medicine that led to improvements in cardiovascular outcomes, cardiovascular disease (CVD) remains the leading cause of mortality and morbidity globally. Thus, there is an urgent need for new approaches to improve CVD drug treatments. As the development time and cost of drug discovery to clinical application are excessive, alternate strategies for drug development are warranted. Among these are included computational approaches based on omics data for drug repositioning, which have attracted increasing attention. In this work, we developed an adjusted similarity measure implemented by the algorithm SAveRUNNER to reposition drugs for cardiovascular diseases while, at the same time, considering the side effects of drug candidates. We analyzed nine cardiovascular disorders and two side effects. We formulated both disease disorders and side effects as network modules in the human interactome, and considered those drug candidates that are proximal to disease modules but far from side-effects modules as ideal. Our method provides a list of drug candidates for cardiovascular diseases that are unlikely to produce common, adverse side-effects. This approach incorporating side effects is applicable to other diseases, as well.

Automated summary

Despite advancements in modern medicine, cardiovascular disease continues to be the leading cause of death and illness worldwide. This article highlights the need for new approaches to improve drug treatments for cardiovascular disease. The study focuses on using computational methods based on omics data to reposition drugs and considers the side effects of drug candidates. The method provides a list of drug candidates for cardiovascular disease that are unlikely to produce common adverse side effects, and this approach can be applicable to other diseases as well.