Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer’s disease

Autor: Shingo Tsuji, Takeshi Hase, Ayako Yachie-Kinoshita, Taiko Nishino, Samik Ghosh, Masataka Kikuchi, Kazuro Shimokawa, Hiroyuki Aburatani, Hiroaki Kitano, Hiroshi Tanaka
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-15 (2021)
Druh dokumentu: article
ISSN: 1758-9193
DOI: 10.1186/s13195-021-00826-3
Popis: Abstract Background Identifying novel therapeutic targets is crucial for the successful development of drugs. However, the cost to experimentally identify therapeutic targets is huge and only approximately 400 genes are targets for FDA-approved drugs. As a result, it is inevitable to develop powerful computational tools that can identify potential novel therapeutic targets. Fortunately, the human protein-protein interaction network (PIN) could be a useful resource to achieve this objective. Methods In this study, we developed a deep learning-based computational framework that extracts low-dimensional representations of high-dimensional PIN data. Our computational framework uses latent features and state-of-the-art machine learning techniques to infer potential drug target genes. Results We applied our computational framework to prioritize novel putative target genes for Alzheimer’s disease and successfully identified key genes that may serve as novel therapeutic targets (e.g., DLG4, EGFR, RAC1, SYK, PTK2B, SOCS1). Furthermore, based on these putative targets, we could infer repositionable candidate-compounds for the disease (e.g., tamoxifen, bosutinib, and dasatinib). Conclusions Our deep learning-based computational framework could be a powerful tool to efficiently prioritize new therapeutic targets and enhance the drug repositioning strategy.
Databáze: Directory of Open Access Journals