DeepMHCII: a novel binding core-aware deep interaction model for accurate MHC-II peptide binding affinity prediction.

MOTIVATION: Computationally predicting major histocompatibility complex (MHC)-peptide binding affinity is an important problem in immunological bioinformatics. Recent cutting-edge deep learning-based methods for this problem are unable to achieve satisfactory performance for MHC class II molecules. This is because such methods generate the input by simply concatenating the two given sequences: (the estimated binding core of) a peptide and (the pseudo sequence of) an MHC class II molecule, ignoring biological knowledge behind the interactions of the two molecules. We thus propose a binding core-aware deep learning-based model, DeepMHCII, with a binding interaction convolution layer, which allows to integrate all potential binding cores (in a given peptide) with the MHC pseudo (binding) sequence, through modeling the interaction with multiple convolutional kernels. RESULTS: Extensive empirical experiments with four large-scale datasets demonstrate that DeepMHCII significantly outperformed four state-of-the-art methods under numerous settings, such as 5-fold cross-validation, leave one molecule out, validation with independent testing sets and binding core prediction. All these results and visualization of the predicted binding cores indicate the effectiveness of our model, DeepMHCII, and the importance of properly modeling biological facts in deep learning for high predictive performance and efficient knowledge discovery. AVAILABILITY AND IMPLEMENTATION: DeepMHCII is publicly available at https://github.com/yourh/DeepMHCII. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.