Identifying patterns to uncover the importance of biological pathways on known drug repurposing scenarios

Abstract

BackgroundDrug repurposing plays a significant role in bringing effective treatments for certain diseases faster and more cost-effectively. Successful repurposing cases are mostly supported by a classical paradigm that stems from de novo drug development. This paradigm is based on the "one-drug-one-target-one-disease" idea. It consists of designing drugs specifically for a single disease and its drugs gene target. In this article, we investigated the use of biological pathways as potential elements to achieve effective drug repurposing. MethodsConsidering a total of 4.214 successful cases of drug repurposing, we identified cases in which biological pathways serve as the underlying basis for successful repurposing, referred to as DREBIOP. Once the repurposing cases based on pathways were identified, we studied the inherent patterns within them by considering the different biological elements associated with this dataset, as well as the pathways involved in these cases. Furthermore, we obtained gene-disease association values to demonstrate the diminished significance of the drugs gene target in these repurposing cases. To achieve this, we compared the values obtained for the DREBIOP set with the overall association values found in DISNET, as well as with the drugs target gene (DREGE) based repurposing cases using the Mann-Whitney U Test. ResultsA collection of drug repurposing cases, known as DREBIOP, was identified as a result. DREBIOP cases exhibit distinct characteristics when compared to DREGE cases. Notably, DREBIOP cases are associated with a higher number of biological pathways, with Vitamin D Metabolism and ACE inhibitor being the most prominent pathways involved. Additionally, it was observed that the association values of GDAs in DREBIOP cases are significantly lower than those in DREGE cases (p-value View larger version (20K): org.highwire.dtl.DTLVardef@187d2ceorg.highwire.dtl.DTLVardef@210b96org.highwire.dtl.DTLVardef@17fc4b7org.highwire.dtl.DTLVardef@14c0184_HPS_FORMAT_FIGEXP M_FIG C_FIG