Enhancing Missense Variant Pathogenicity Prediction with MissenseNet: Integrating Structural Insights and ShuffleNet-Based Deep Learning Techniques

The classification of missense variant pathogenicity continues to pose significant challenges in human genetics, necessitating precise predictions of functional impacts for effective disease diagnosis and personalized treatment strategies. Traditional methods, often compromised by suboptimal feature selection and limited generalizability, are outpaced by the enhanced classification model, MissenseNet (Missense Classification Network). This model, advancing beyond standard predictive features, incorporates structural insights from AlphaFold2 protein predictions, thus optimizing structural data utilization. MissenseNet, built on the ShuffleNet architecture, incorporates an encoder-decoder framework and a Squeeze-and-Excitation (SE) module designed to adaptively adjust channel weights and enhance feature fusion and interaction. The model’s efficacy in classifying pathogenicity has been validated through superior accuracy compared to conventional methods and by achieving the highest areas under the Receiver Operating Characteristic (ROC) and Precision-Recall (PR) curves (Area Under the Curve and Area Under the Precision-Recall Curve) in an independent test set, thus underscoring its superiority.