AlgPred 2.0 is a web server developed for predicting allergenic proteins and allergenic regions in a protein. It is an updated version of AlgPred developed in 2006. The dataset used for training, testing and validation consists of 10 075 allergens and 10 075 non-allergens. In addition, 10 451 experimentally validated immunoglobulin E (IgE) epitopes were used to identify antigenic regions in a protein. All models were trained on 80% of data called training dataset, and the performance of models was evaluated using 5-fold cross-validation technique. The performance of the final model trained on the training dataset was evaluated on 20% of data called validation dataset; no two proteins in any two sets have more than 40% similarity. First, a Basic Local Alignment Search Tool (BLAST) search has been performed against the dataset, and allergens were predicted based on the level of similarity with known allergens. Second, IgE epitopes obtained from the IEDB database were searched in the dataset to predict allergens based on their presence in a protein. Third, motif-based approaches like multiple EM for motif elicitation/motif alignment and search tool have been used to predict allergens. Fourth, allergen prediction models have been developed using a wide range of machine learning techniques. Finally, the ensemble approach has been used for predicting allergenic protein by combining prediction scores of different approaches. Our best model achieved maximum performance in terms of area under receiver operating characteristic curve 0.98 with Matthew’s correlation coefficient 0.85 on the validation dataset. A web server AlgPred 2.0 has been developed that allows the prediction of allergens, mapping of IgE epitope, motif search and BLAST search (https://webs.iiitd.edu.in/raghava/algpred2/).

Interleukin 6 (IL-6) is a pro-inflammatory cytokine that stimulates acute phase responses, hematopoiesis and specific immune reactions. Recently, it was found that the IL-6 plays a vital role in the progression of COVID-19, which is responsible for the high mortality rate. In order to facilitate the scientific community to fight against COVID-19, we have developed a method for predicting IL-6 inducing peptides/epitopes. The models were trained and tested on experimentally validated 365 IL-6 inducing and 2991 non-inducing peptides extracted from the immune epitope database. Initially, 9149 features of each peptide were computed using Pfeature, which were reduced to 186 features using the SVC-L1 technique. These features were ranked based on their classification ability, and the top 10 features were used for developing prediction models. A wide range of machine learning techniques has been deployed to develop models. Random Forest-based model achieves a maximum AUROC of 0.84 and 0.83 on training and independent validation dataset, respectively. We have also identified IL-6 inducing peptides in different proteins of SARS-CoV-2, using our best models to design vaccine against COVID-19. A web server named as IL-6Pred and a standalone package has been developed for predicting, designing and screening of IL-6 inducing peptides (https://webs.iiitd.edu.in/raghava/il6pred/).

The blood–brain barrier is a major obstacle in treating brain-related disorders, as it does not allow the delivery of drugs into the brain. We developed a method for predicting blood–brain barrier penetrating peptides to facilitate drug delivery into the brain. These blood–brain barrier penetrating peptides (B3PPs) can act as therapeutics, as well as drug delivery agents. We trained, tested, and evaluated our models on blood–brain barrier peptides obtained from the B3Pdb database. First, we computed a wide range of peptide features. Then, we selected relevant peptide features. Finally, we developed numerous machine-learning-based models for predicting blood–brain barrier peptides using the selected features. The random-forest-based model performed the best with respect to the top 80 selected features and achieved a maximal 85.08% accuracy with an AUROC of 0.93. We also developed a webserver, B3pred, that implements our best models. It has three major modules that allow users to predict/design B3PPs and scan B3PPs in a protein sequence.

Most of the existing methods developed for predicting antibacterial peptides (ABPs) are mostly designed to target either gram-positive or gram-negative bacteria. In this study, we describe a method that allows us to predict ABPs against gram-positive, gram-negative, and gram-variable bacteria. Firstly, we developed an alignment-based approach using BLAST to identify ABPs and achieved poor sensitivity. Secondly, we employed a motif-based approach to predict ABPs and obtained high precision with low sensitivity. To address the issue of poor sensitivity, we developed alignment-free methods for predicting ABPs using machine/deep learning techniques. In the case of alignment-free methods, we utilized a wide range of peptide features that include different types of composition, binary profiles of terminal residues, and fastText word embedding. In this study, a five-fold cross-validation technique has been used to build machine/deep learning models on training datasets. These models were evaluated on an independent dataset with no common peptide between training and independent datasets. Our machine learning-based model developed using the amino acid binary profile of terminal residues achieved maximum AUC 0.93, 0.98, and 0.94 for gram-positive, gram-negative, and gram-variable bacteria, respectively, on an independent dataset. Our method performs better than existing methods when compared with existing approaches on an independent dataset. A user-friendly web server, standalone package and pip package have been developed to facilitate peptide-based therapeutics.