Drug-target-ADR Network and Possible Implications of Structural Variants in Adverse Events

Abstract

Adverse drug reactions (ADRs) are of major concern in drug safety. However, due to the biological complexity of human systems, understanding the underlying mechanisms involved in development of ADRs remains a challenging task. Here, we applied network sciences to analyze a tripartite network between 1000 drugs, 1407 targets, and 6164 ADRs. It allowed us to suggest drug targets susceptible to be associated to ADRs and organs, based on the system organ class (SOC). Furthermore, a score was developed to determine the contribution of a set of proteins to ADRs. Finally, we identified proteins that might increase the susceptibility of genes to ADRs, on the basis of knowledge about genomic structural variation in genes encoding proteins targeted by drugs. Such analysis should pave the way to individualize drug therapy and precision medicine.