Network based prediction of drug-drug interactions

摘要

Drug-drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for patient safety but also very challenging. In recent years, several drugs have been withdrawn from the market due to interaction related Adverse Events (AEs). Currently, the US Food and Drug Administration (FDA) and pharmaceutical companies are showing great interest in the development of improved tools for identifying DDIs. We describe a predictive model, applicable on a large scale to predict novel DDIs based on similarity of drug interaction candidates to drugs involved in established DDIs. The underlying assumption is that if drug A and drug B interact to produce a specific biological effect, then drugs similar to drug A (or drug B) are likely to interact with drug B (or drug A) to produce the same effect. We constructed a 352 drug DDI network from a 2011 snapshot of a widely-used drug safety database, which contains 3 700 established DDIs, and used it to develop the proposed model for predicting future DDIs. The target similarity for all selected pairs of drugs in DrugBank was computed to identify DDI candidates. The proposed model mainly follows two distinct approaches: the first one is `Which forces the preservation of existing (known) DDIs' and the other one is `without forced to preserve existing DDIs.' Predictions were made under each of these approaches using three different techniques: target similarity score, side effect similarity (P-score) and resulting score. The methodology was evaluated using Drugbank 2014 snapshot as a gold standard for the same set of drugs. The proposed model generates novel DDIs with an average accuracy of 95% for force to preserve existing (known) DDIs. Average accuracy for without forced to preserve existing DDIs is 92%. These two approaches also give average AUC (Area Under the Curve) of 0.9834 and 0.8651 respectively. The results presented in this study demonstrate the usefulness of the proposed network based drug-drug interaction methodology as a promising approach. The method described in this article is very simple, efficient, and biologically sound.