IntegralVac: A Machine Learning-Based Comprehensive Multivalent Epitope Vaccine Design Method.

ABSTRACT

In the growing field of vaccine design for COVID and cancer research, it is essential to predict accurate peptide binding affinity and immunogenicity. We developed a comprehensive machine learning method, 'IntegralVac,' by integrating three existing deep learning tools DeepVacPred, MHCSeqNet, and HemoPI. IntegralVac makes predictions for single and multivalent cancer and COVID-19 epitopes without manually selecting epitope prediction possibilities. We performed several rounds of optimization before integration, then re-trained IntegralVac for multiple datasets. We validated the IntegralVac with 4500 human cancer MHC I peptides obtained from the Immune Epitope Database (IEDB) and with cancer and COVID epitopes previously selected in our laboratory. The other data referenced from existing deep learning tools served as a positive control to ensure successful prediction was possible. As evidenced by increased accuracy and AUC, IntegralVac improved the prediction rate of top-ranked epitopes. We also examined the compatibility between other servers' clinical checkpoint filters and IntegralVac. This was to ensure that the other servers had a means for predicting additional checkpoint filters that we wanted to implement in IntegralVac. The clinical checkpoint filters, including allergenicity, antigenicity, and toxicity, were used as additional predictors to improve IntegralVac's prediction accuracy. We generated immunogenicity scores by cross-comparing sequence inputs with each other and determining the overlap between each individual peptide sequence. The IntegralVac increased the immunogenicity prediction accuracy to 90.1% AUC and the binding affinity accuracy to 95.4% compared to the control NetMHCPan server. The IntegralVac opens new avenues for future in silico methods, by building upon established models for continued prediction accuracy improvement.