Modeling drug mechanism of action with large scale gene-expression profiles using GPAR, an artificial intelligence platform

• Main Authors: Gao, S. (Author), Han, L. (Author), Liu, G. (Author), Luo, D. (Author), Shan, G. (Author), Xiao, Z. (Author), Zhang, Y. (Author), Zhou, W. (Author)
• Format: Article
• Language: English
• Published: BioMed Central Ltd 2021
• Subjects: artificial intelligence; Artificial Intelligence; biology; Birds; Collaborative tools; Computational Biology; Cross-validation tests; Databases, Genetic; Deep learning; drug; Forecasting; Gene expression; Gene expression profiles; Gene set enrichment analysis; genetic database; genetics; L1000; Learning approach; Learning systems; Machine learning methods; Mechanism of action; MOA; Model performance; Pharmaceutical Preparations; pharmacology; Pharmacology; Predictive analytics; software; Software; transcriptome; Transcriptome
• Online Access: View Fulltext in Publisher

 Background: Querying drug-induced gene expression profiles with machine learning method is an effective way for revealing drug mechanism of actions (MOAs), which is strongly supported by the growth of large scale and high-throughput gene expression databases. However, due to the lack of code-free and user friendly applications, it is not easy for biologists and pharmacologists to model MOAs with state-of-art deep learning approach. Results: In this work, a newly developed online collaborative tool, Genetic profile-activity relationship (GPAR) was built to help modeling and predicting MOAs easily via deep learning. The users can use GPAR to customize their training sets to train self-defined MOA prediction models, to evaluate the model performances and to make further predictions automatically. Cross-validation tests show GPAR outperforms Gene set enrichment analysis in predicting MOAs. Conclusion: GPAR can serve as a better approach in MOAs prediction, which may facilitate researchers to generate more reliable MOA hypothesis. © 2020, The Author(s).