Caraca-Valente Hernandez, J. P.

bioRxiv2023

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

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 < 0.05). ConclusionsBiological pathways assume a pivotal role in drug repurposing cases. This investigation successfully revealed patterns that distinguish drug repurposing instances associated with biological pathways. These identified patterns can be applied to any known repurposing case, enabling the detection of pathway-based repurposing scenarios or the classical paradigm. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/572035v1_ufig1.gif" ALT="Figure 1"> 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

bioinformatics↗

bioRxiv2022

Drug repositioning with gender perspective focused on Adverse Drug Reactions

Drug repositioning is a novel, useful, and crucial technique to find new uses for existing drugs. In this field of study, when the clinical trials necessary to obtain successful drug repositioning have been carried out, the female gender has not been given much consideration. Thus far, the participation of women in clinical trials has been very limited. There were several argued reasons to exclude them from trials, like the likelihood of pregnancy or sudden hormonal changes. This has meant that for a long time the adverse effects of a drug on women were unknown. Scientifically, it was known that due to the biological processes of pharmacokinetics and pharmacodynamics, the response to drugs was not the same in both genders, but despite this evidence, there is still no difference in the dosage or form of using a drug between men and women. In this study, we made a preliminary analysis where the main goal is to investigate gender differences within the drug repositioning field through the adverse effects produced by such treatments. A special section on specific cases of drug repositioning in rare diseases will also be considered to carry out the same verification previously mentioned in the text.

bioinformatics↗