gene2drug: a computational tool for pathway-based rational drug repositioning

• DOI: 10.1093/bioinformatics/btx800
• Publication Date: 2017-12-10T20:06:35Z
• Authors: Francesco Napolitano; Diego Carrella; Barbara Mandriani; Sandra Pisonero-V...; Francesco Sirci; Diego L Medina; Nicola Brunetti-P...; Diego di Bernardo
• Keywords: TFEB; Drug repositioning; NRF1

Drug repositioning has been proposed as an effective shortcut to drug discovery. The availability of large collections transcriptional responses drugs enables computational approaches directly based on measured molecular effects.We introduce a novel methodology for rational repositioning, which exploits the following treatment with small molecule. Specifically, given therapeutic target gene, prioritization potential is obtained by assessing their impact transcription genes in pathway(s) including target. We performed silico validation and comparison state-of-art technique similar principles. next experimental two different real-case scenarios: (i) upregulation glutamate-pyruvate transaminase (GPT), shown induce reduction oxalate levels mouse model primary hyperoxaluria, (ii) activation factor TFEB, master regulator lysosomal biogenesis autophagy, whose modulation may be beneficial neurodegenerative disorders.A web tool Gene2drug freely available at http://gene2drug.tigem.it. An R package under development can from https://github.com/franapoli/[e-mail] data are Bioinformatics online.