A Network Biology Approach to Understand Combination of Drugs

Drug combination is becoming a popular strategy for combating complex traits, where combination of drugs improves therapy significantly over single agents. However, it is a challenging task to identify the optimal and effective combinations of drugs due to explosion of huge number of possible combinations among drugs. Therefore, it is necessary to understand the mechanisms underlying drug combinations. In this work, a network biology approach is presented to investigate the combination drugs and their target proteins in the context of protein interaction network, human pathway and functional annotations, in order to better understand the underlying rules of drug combinations. Our results indicate that the target proteins of effective combination drugs tend to be close in the protein interaction network, are more likely to be involved in the same pathways and their target proteins tend to have similar biological functions. These findings shed lights on the underlying principles of drug combinations and are helpful for identifying possible effective combinations of drugs.