PRMxAI: protein arginine methylation sites prediction based on amino acid spatial distribution using explainable artificial intelligence

Abstract

Abstract Background Protein methylation, a post-translational modification, is crucial in regulating various cellular functions. Arginine methylation is required to understand crucial biochemical activities and biological functions, like gene regulation, signal transduction, etc. However, some experimental methods, including Chip–Chip, mass spectrometry, and methylation-specific antibodies, exist for the prediction of methylated proteins. These experimental methods are expensive and tedious. As a result, computational methods based on machine learning play an efficient role in predicting arginine methylation sites. Results In this research, a novel method called PRMxAI has been proposed to predict arginine methylation sites. The proposed PRMxAI extract sequence-based features, such as dipeptide composition, physicochemical properties, amino acid composition, and information theory-based features (Arimoto, Havrda-Charvat, Renyi, and Shannon entropy), to represent the protein sequences into numerical format. Various machine learning algorithms are implemented to select the better classifier, such as Decision trees, Naive Bayes, Random Forest, Support vector machines, and K-nearest neighbors. The random forest algorithm is selected as the underlying classifier for the PRMxAI model. The performance of PRMxAI is evaluated by employing 10-fold cross-validation, and it yields 87.17% and 90.40% accuracy on mono-methylarginine and di-methylarginine data sets, respectively. This research also examines the impact of various features on both data sets using explainable artificial intelligence. Conclusions The proposed PRMxAI shows the effectiveness of the features for predicting arginine methylation sites. Additionally, the SHapley Additive exPlanation method is used to interpret the predictive mechanism of the proposed model. The results indicate that the proposed PRMxAI model outperforms other state-of-the-art predictors.