A novel ensemble fuzzy classification model in SARS-CoV-2 B-cell epitope identification for development of protein-based vaccine

B-cell epitope prediction research has received growing interest since the development of the first method. B-cell epitope identification with the aid of an accurate prediction method is one of the most important steps in epitope-based vaccine development, immunodiagnostic testing, antibody production, disease diagnosis, and treatment. Nevertheless, using experimental methods in epitope mapping is very time-consuming, costly, and labor-intensive. Therefore, although successful predictions with in silico methods are very important in epitope prediction, there are limited studies in this area. The aim of this study is to propose a new approach for successfully predicting B-cell epitopes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, the SARS-CoV B-cell epitope prediction performances of different fuzzy learning classification models genetic cooperative competitive learning (GCCL), fuzzy genetics-based machine learning (GBML), Chi's method (CHI), Ishibuchi's method with weight factor (W), structural learning algorithm on vague environment (SLAVE) and the state-of-the-art ensemble fuzzy classification model were compared. The obtained results showed that the proposed ensemble approach has the lowest error in SARS-CoV B-cell epitope estimation compared to the base fuzzy learners (average error rates; ensemble fuzzy=8.33, GCCL=30.42, GBML=23.82, CHI=29.17, W=46.25, and SLAVE=20.42). SARS-CoV and SARS-CoV-2 have high genome similarities. Therefore, the most successful method determined for SARS-CoV B-cell epitope prediction was used in SARS-CoV-2 cell epitope prediction. Finally, the eventual B-cell epitope prediction results obtained for SARS-CoV-2 with the ensemble fuzzy classification model were compared with the epitope sequences predicted by the BepiPred server and immunoinformatics studies in the literature for the same protein sequences according to VaxiJen 2.0 scores. We hope that the developed epitope prediction method will help design effective vaccines and drugs against future outbreaks of the coronavirus family, especially SARS-CoV-2 and its possible mutations. © 2021 Elsevier B.V.121E326This study was supported by The Scientific and Technological Research Council of Turkey-TÜBİTAK (Project Number: 121E326 ).This study was supported by The Scientific and Technological Research Council of Turkey-T?B?TAK (Project Number: 121E326)

A new approach for determining SARS-CoV-2 epitopes using machine learning-based in silico methods

The emergence of machine learning-based in silico tools has enabled rapid and high-quality predictions in the biomedical field. In the COVID-19 pandemic, machine learning methods have been used in many topics such as predicting the death of patients, modeling the spread of infection, determining future effects, diagnosis with medical image analysis, and forecasting the vaccination rate. However, there is a gap in the literature regarding identifying epitopes that can be used in fast, useful, and effective vaccine design using machine learning methods and bioinformatics tools. Machine learning methods can give medical biotechnologists an advantage in designing a faster and more successful vaccine. The motivation of this study is to propose a successful hybrid machine learning method for SARS-CoV-2 epitope prediction and to identify nonallergen, nontoxic, antigen peptides that can be used in vaccine design from the predicted epitopes with bioinformatics tools. The identified epitopes will be effective not only in the design of the COVID-19 vaccine but also against viruses from the SARS family that may be encountered in the future. For this purpose, epitope prediction performances of random forest, support vector machine, logistic regression, bagging with decision tree, k-nearest neighbor and decision tree methods were examined. In the SARS-CoV and B-cell datasets used for education in the study, epitope estimation was performed again after the datasets were balanced with the synthetic minority oversampling technique (SMOTE) method since the epitope class samples were in the minority compared to the nonepitope class. The experimental results obtained were compared and the most successful predictions were obtained with the random forest (RF) method. The epitope prediction performance in balanced datasets was found to be higher than that in the original datasets (94.0% AUC and 94.4% PRC for the SMOTE-SARS-CoV dataset; 95.6% AUC and 95.3% PRC for the SMOTE-B-cell dataset). In this study, 252 peptides out of 20312 peptides were determined to be epitopes with the SMOTE-RF-SVM hybrid method proposed for SARS-CoV-2 epitope prediction. Determined epitopes were analyzed with AllerTOP 2.0, VaxiJen 2.0 and ToxinPred tools, and allergic, nonantigen, and toxic epitopes were eliminated. As a result, 11 possible nonallergic, high antigen and nontoxic epitope candidates were proposed that could be used in protein-based COVID-19 vaccine design (“VGGNYNY”, “VNFNFNGLTG”, “RQIAPGQTGKI”, “QIAPGQTGKIA”, “SYECDIPIGAGI”, “STFKCYGVSPTKL”, “GVVFLHVTYVPAQ”, “KNHTSPDVDLGDI”, “NHTSPDVDLGDIS”, “AGAAAYYVGYLQPR”, “KKSTNLVKNKCVNF”). It is predicted that the few epitopes determined by machine learning-based in silico methods will help biotechnologists design fast and accurate vaccines by reducing the number of trials in the laboratory environment. © 2022 Elsevier LtdTürkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK: 121E326This study was supported by Turkish Scientific and Technical Research Council, Turkey-TÜBİTAK (Project Number: 121E326).This study was supported by Turkish Scientific and Technical Research Council, Turkey -TÜBİTAK (Project Number: 121E326 )