Accurate Prediction of Antifreeze Protein from Sequences through Natural Language Text Processing and Interpretable Machine Learning Approaches

Antifreeze proteins (AFPs) bind to growing iceplanes owing to their structural complementarity nature, thereby inhibiting the ice-crystal growth by thermal hysteresis. Classification of AFPs from sequence is a difficult task due to their low sequence similarity, and therefore, the usual sequence similarity algorithms, like Blast and PSI-Blast, are not efficient. Here, a method combining n-gram feature vectors and machine learning models to accelerate the identification of potential AFPs from sequences is proposed. All these n-gram features are extracted from the K-mer counting method. The comparative analysis reveals that, among different machine learning models, Xgboost outperforms others in predicting AFPs from sequence when penta-mers are used as a feature vector. When tested on an independent dataset, our method performed better compared to other existing ones with sensitivity of 97.50%, recall of 98.30%, and f1 score of 99.10%. Further, we used the SHAP method, which provides important insight into the functional activity of AFPs.