Drug Target Protein-Protein Interaction Networks: A Systematic Perspective

The identification and validation of drug targets is crucial in biomedical research. Most recently, lots of studies have been conducted on analyzing drug target features aiming at getting a better understanding on principles of their mechanisms. But most of them are based on either strong biological hypotheses or the chemical and physical properties of those targets separately. In this paper, we examined three main ways to understand the functional biomolecules based on the topological features of drug targets. By comparison between two types of proteins (targets and common proteins) of the protein-protein interactions (PPI) network, the results show there are no significant differences on intermediary and source functions. It implies the drug targets are neither hub proteins which are dominant, nor the bridge proteins which play an important role on connectivity of the PPI network. On the other hand, according with some special topological structures of the drug targets, there are significant differences between known targets and other proteins. Furthermore the drug targets mainly belong to three typical communities based on their modularity. Meanwhile, the most targets are in 6, 9, 12, 16, 18 cores of the PPI network. These topological features are helpful to understand how the drug targets work in the PPI network. Particularly it is a reasonably alternative way to predict potential targets or extract non-targets to test a new drug target more efficiently and economically. By this way, a drug target’s homologue set are predicted in the paper. It contains 102 proteins as potential target proteins, some of which were recently published as new drug targets.

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