FEATURE-pHLA: Physico-chemical features efficiently predict peptide-HLA binding affinity

Human leukocyte antigen or HLA plays a crucial role in the recognition of antigenic peptides as this binding is responsible for subsequent immune response by eliciting T-cell activation. Accurate prediction of peptide-HLA binding affinity is imperative for facilitating vaccine development and immunotherapies. Recent advancements in transformer-based models and protein language models in predicting peptide-HLA interactions have shown significant improvements. Current methodologies rely on deep learning methods and GPU-intensive computations. We propose a simple and computationally cheaper method that demonstrates efficacy. Our tree-based model, named FEATUREPHLA, utilizes the physico-chemical fingerprints obtained from peptides and HLA sequences and is highly interpretable.Our goal was to estimate the predictive efficacy of these physico-chemical features for the task of peptide-HLA binding prediction. Our proposed method outperforms other methods on experimentally verified peptide-HLA binders from the HPV vaccine data securing the highest number of true positives and the lowest number of false negatives, thereby, showcasing its predictive power on real-world scenarios. Our study reveals the relevance of biology-inspired features for the calculation of molecular interactions and lays the groundwork towards developing more accurate biology-informed predictive models.