PredPS: Attention-based graph neural network for predicting stability of compounds in human plasma

• Published in: Computational and structural biotechnology journal 2023-01, Vol.21, p.3532-3539
• Main Authors: Jang, Woo Dae, Jang, Jidon, Song, Jin Sook, Ahn, Sunjoo, Oh, Kwang-Seok
• Format: Article
• Language: English
• Subjects: ADME; Artificial intelligence; Attention analysis; Drug discovery; Graph neural network; Machine learning; Pharmacokinetic property; Plasma stability; Software/Web Server
• ISSN: 2001-0370; 2001-0370
• DOI: 10.1016/j.csbj.2023.07.008

Stability of compounds in the human plasma is crucial for maintaining sufficient systemic drug exposure and considered an essential factor in the early stages of drug discovery and development. The rapid degradation of compounds in the plasma can result in poor in vivo efficacy. Currently, there are no open-source software programs for predicting human plasma stability. In this study, we developed an attention-based graph neural network, PredPS to predict the plasma stability of compounds in human plasma using in-house and open-source datasets. The PredPS outperformed the two machine learning and two deep learning algorithms that were used for comparison indicating its stability-predicting efficiency. PredPS achieved an area under the receiver operating characteristic curve of 90.1%, accuracy of 83.5%, sensitivity of 82.3%, and specificity of 84.6% when evaluated using 5-fold cross-validation. In the early stages of drug discovery, PredPS could be a helpful method for predicting the human plasma stability of compounds. Saving time and money can be accomplished by adopting an in silico-based plasma stability prediction model at the high-throughput screening stage. The source code for PredPS is available at https://bitbucket.org/krict-ai/predps and the PredPS web server is available at https://predps.netlify.app. [Display omitted]