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

• Published in: Scientific reports Vol. 11; no. 1; pp. 5585 - 14
• Main Authors: Moore, Robert, Puniya, Bhanwar Lal, Powers, Robert, Guda, Chittibabu, Bayles, Kenneth W., Berkowitz, David B., Helikar, Tomáš
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/114/2404; 631/154/555; 631/337/2019; Drug development; Gamma rays; Gelatinase B; Gene expression; Humanities and Social Sciences; Long-term effects; multidisciplinary; Radiation; Science; Science (multidisciplinary); Therapeutic targets; ZAP-70 protein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-85044-5

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 coexpression 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.