A Drug Repurposing Method Based on Drug-Drug Interaction Networks and Using Energy Model Layouts

Abstract

Complex network representations of reported drug-drug interactions foster computational strategies that can infer pharmacological functions which, in turn, create incentives for drug repositioning. Here, we use Gephi (a platform for complex network visualization and analysis) to represent a drug-drug interaction network with drug interaction information from DrugBank 4.1. Both modularity class- and force-directed layout ForceAtlas2 are employed to generate drug clusters which correspond to nine specific drug properties. Most drugs comply with their cluster’s dominant property; however, some of them seem not to be in a proper position (i.e., in accordance with their already known functions). Such cases, along with cases of drugs that are topologically placed in the overlapping or bordering zones between clusters, may indicate previously unaccounted pharmacologic functions, thus leading to potential repositionings. Out of the 1141 drugs with relevant information on their interactions in DrugBank 4.1, we confirm the predicted properties for 85% of the drugs. The high prediction rate of our methodology suggests that, at least for some of the 15% drugs that seem to be inconsistent with the predicted property, we can get very good repositioning hints. As such, we present illustrative examples of recovered well-known repositionings, as well as recently confirmed pharmacological properties.