PRITrans: A Transformer-Based Approach for the Prediction of the Effects of Missense Mutation on Protein–RNA Interactions

Abstract

Protein–RNA interactions are essential to many cellular functions, and missense mutations in RNA-binding proteins can disrupt these interactions, often leading to disease. To address this, we developed PRITrans, a specialized computational method aimed at predicting the effects of missense mutations on protein–RNA interactions, which is vital for understanding disease mechanisms and advancing molecular biology research. PRITrans is a novel deep learning model designed to predict the effects of missense mutations on protein–RNA interactions, which employs a Transformer architecture enhanced with multiscale convolution modules for comprehensive feature extraction. Its primary innovation lies in integrating protein language model embeddings with a deep feature fusion strategy, effectively handling high-dimensional feature representations. By utilizing multi-layer self-attention mechanisms, PRITrans captures nuanced, high-level sequence information, while multiscale convolutions extract features across various depths, thereby enhancing predictive accuracy. Consequently, this architecture enables significant improvements in ΔΔG prediction compared to traditional approaches. We validated PRITrans using three different cross-validation strategies on two newly reconstructed mutation datasets, S315 and S630 (containing 315 forward and 315 reverse mutations). The results consistently demonstrated PRITrans’s strong performance on both datasets. PRITrans demonstrated strong predictive capability, achieving a Pearson correlation coefficient of 0.741 and a root mean square error (RMSE) of 1.168 kcal/mol on the S630 dataset. Moreover, its robust performance extended to independent test sets, achieving a Pearson correlation of 0.699 and an RMSE of 1.592 kcal/mol. These results underscore PRITrans’s potential as a powerful tool for protein-RNA interaction studies. Moreover, when tested against existing prediction methods on an independent dataset, PRITrans showed improved predictive accuracy and robustness.