Correlating adverse drug reactions with biological pathways in humans

Abstract

It has been well recognized that adverse drug reactions (ADRs) are a significant cause of morbidity and mortality. There is a growing interest in investigating biological pathways involved in cellular response to drugs. Based on examining the co-occurrence of drugs in pathway activity and ADR profiles, in this paper, we propose a new method to explore the relationship between biological pathways and ADRs at a large scale. Using sparse canonical correlation analysis of 495 drugs with two profiles for 173 pathways and 1385 ADRs, a total of 80 correlated sets of pathways and ADRs were extracted. To evaluate the performance of our method, extracted correlated components were used to retrieve known ADR profiles from drug pathway profiles using a 5-fold cross validation. A relatively high prediction performance (AUC: 0.881) was achieved. This work provides a foundation for future investigation of ADRs in the context of biological pathways under different conditions.