Data Mining for Drug Repurposing and New Targets Identification for Radioprotection

Abstract

Ionising radiation (IR) is responsible for various types of tissue injury leading to morbidity at low doses and mortality at high radiation exposure. Although many radioprotective and pharmacological agents are being tested for decreasing radiation injury, however, the availability of Amifostine as the only clinically used radioprotector with limited indication has prompted us to find out new potential molecules through drugs repurposing for protecting or decreasing radiation damage by data mining. In this work we have used text-mining based network generation approach to find out the gene targets of radioprotectors under evaluation by Agilent Literature Search app in Cytoscape. Extracted genes were evaluated for their association with radiation in Radiation Genes database. These genes were searched against therapeutic drugs and molecules under clinical trial in the Drug Gene Interaction database. We found that most of the radiation target genes were involved in cell death, proliferation, homeostasis, cell cycle and cancer pathways. Many of these genes were druggable and could be targeted by the drugs under clinical research, whereas there were few genes (new targets), which were never considered for radioprotective drug development. This study would likely help in repurposing of identified drugs for use in the event of radiation fallout, keeping in mind that no radiation medical countermeasure for acute radiation syndrome has been approved by the US FDA for use in humans. Results also revealed new target genes for drug targeting and indicates use of similar pipeline in other pathologies for drug repurposing and development.