A hybrid method for discovering interferon-gamma inducing peptides in human and mouse

Interferon-gamma (IFN-γ) is a versatile pleiotropic cytokine essential for both innate and adaptive immune responses. It exhibits both pro-inflammatory and anti-inflammatory properties, making it a promising therapeutic candidate for treating various infectious diseases and cancers. We present IFNepitope2, a host-specific technique to annotate IFN-γ inducing peptides, it is an updated version of IFNepitope introduced by Dhanda et al. In this study, dataset used for developing prediction method contain experimentally validated 25,492 and 7983 IFN-γ inducing peptides in human and mouse host, respectively. In initial phase, machine learning techniques have been exploited to develop classification model using wide range of peptide features. Further, to improve machine learning based models or alignment free models, we explore potential of similarity-based technique BLAST. Finally, a hybrid model has been developed that combine best machine learning based model with BLAST. In most of the case, models based on extra tree perform better than other machine learning techniques. In case of peptide features, compositional feature particularly dipeptide composition performs better than one-hot encoding or binary profile. Our best machine learning based models achieved AUROC 0.89 and 0.83 for human and mouse host, respectively. The hybrid model achieved the AUROC 0.90 and 0.85 for human and mouse host, respectively. All models have been evaluated on an independent/validation dataset not used for training or testing these models. Newly developed method performs better than existing method on independent dataset. The major objective of this study is to predict, design and scan IFN-γ inducing peptides, thus server/software have been developed ( https://webs.iiitd.edu.in/raghava/ifnepitope2/ ). This method is also available as standalone at https://github.com/raghavagps/ifnepitope2 and python package index at https://pypi.org/project/ifnepitope2/ .