Integrative network analyses of transcriptomics data reveal potential drug targets for acute radiation syndrome

Authors

Robert Moore, University of Nebraska-LincolnFollow
Bhanwar Lal Puniya, University of Nebraska-LincolnFollow
Robert Powers, University of Nebraska-LincolnFollow
Chittibabu Guda, University of Nebraska Medical Center
Kenneth W. Bayles, University of Nebraska Medical Center
David Berkowitz, University of Nebraska-LincolnFollow
Tomas Helikar, University of Nebraska-LincolnFollow

Date of this Version

2021

Citation

Moore, R., Puniya, B.L., Powers, R. et al. Integrative network analyses of transcriptomics data reveal potential drug targets for acute radiation syndrome. Sci Rep 11, 5585 (2021). https://doi.org/10.1038/s41598-021-85044-5

Comments

CC-BY

Abstract

Recent political unrest has highlighted the importance of understanding the short- and long-term effects of gamma-radiation exposure on human health and survivability. In this regard, effective treatment for acute radiation syndrome (ARS) is a necessity in cases of nuclear disasters. Here, we propose 20 therapeutic targets for ARS identified using a systematic approach that integrates gene co-expression networks obtained under radiation treatment in humans and mice, drug databases, disease-gene association, radiation-induced differential gene expression, and literature mining. By selecting gene targets with existing drugs, we identified potential candidates for drug repurposing. Eight of these genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, CBR1, ZAP70, IDH3B) were confirmed through literature to have shown radioprotective effect upon perturbation. This study provided a new perspective for the treatment of ARS using systems-level gene associations integrated with multiple biological information. The identified genes might provide high confidence drug target candidates for potential drug repurposing for ARS.