Prediction of the synergistic effect of antimicrobial peptides and antimicrobial agents via supervised machine learning

Abstract Background Infectious diseases not only cause severe health problems but also burden the healthcare system. Therefore, the effective treatment of those diseases is crucial. Both conventional approaches, such as antimicrobial agents, and novel approaches, like antimicrobial peptides (AMPs), are used to treat infections. However, due to the drawbacks of current approaches, new solutions are still being investigated. One recent approach is the use of AMPs and antimicrobial agents in combination, but determining synergism is with a huge variety of AMPs time-consuming and requires multiple experimental studies. Machine learning (ML) algorithms are widely used to predict biological outcomes, particularly in the field of AMPs, but no previous research reported on predicting the synergistic effects of AMPs and antimicrobial agents. Results Several supervised ML models were implemented to accurately predict the synergistic effect of AMPs and antimicrobial agents. The results demonstrated that the hyperparameter-optimized Light Gradient Boosted Machine Classifier (oLGBMC) yielded the best test accuracy of 76.92% for predicting the synergistic effect. Besides, the feature importance analysis reveals that the target microbial species, the minimum inhibitory concentrations (MICs) of the AMP and the antimicrobial agents, and the used antimicrobial agent were the most important features for the prediction of synergistic effect, which aligns with recent experimental studies in the literature. Conclusion This study reveals that ML algorithms can predict the synergistic activity of two different antimicrobial agents without the need for complex and time-consuming experimental procedures. The implications support that the ML models may not only reduce the experimental cost but also provide validation of experimental procedures.