TROLLOPE: A novel sequence-based stacked approach for the accelerated discovery of linear T-cell epitopes of hepatitis C virus

PLoS One. 2023 Aug 25;18(8):e0290538. doi: 10.1371/journal.pone.0290538. eCollection 2023.

Abstract

Hepatitis C virus (HCV) infection is a concerning health issue that causes chronic liver diseases. Despite many successful therapeutic outcomes, no effective HCV vaccines are currently available. Focusing on T cell activity, the primary effector for HCV clearance, T cell epitopes of HCV (TCE-HCV) are considered promising elements to accelerate HCV vaccine efficacy. Thus, accurate and rapid identification of TCE-HCVs is recommended to obtain more efficient therapy for chronic HCV infection. In this study, a novel sequence-based stacked approach, termed TROLLOPE, is proposed to accurately identify TCE-HCVs from sequence information. Specifically, we employed 12 different sequence-based feature descriptors from heterogeneous perspectives, such as physicochemical properties, composition-transition-distribution information and composition information. These descriptors were used in cooperation with 12 popular machine learning (ML) algorithms to create 144 base-classifiers. To maximize the utility of these base-classifiers, we used a feature selection strategy to determine a collection of potential base-classifiers and integrated them to develop the meta-classifier. Comprehensive experiments based on both cross-validation and independent tests demonstrated the superior predictive performance of TROLLOPE compared with conventional ML classifiers, with cross-validation and independent test accuracies of 0.745 and 0.747, respectively. Finally, a user-friendly online web server of TROLLOPE (http://pmlabqsar.pythonanywhere.com/TROLLOPE) has been developed to serve research efforts in the large-scale identification of potential TCE-HCVs for follow-up experimental verification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Epitopes, T-Lymphocyte
  • Hepacivirus / genetics
  • Hepatitis C*
  • Hepatitis C, Chronic*
  • Humans

Substances

  • Epitopes, T-Lymphocyte

Grants and funding

This project is funded by National Research Council of Thailand (NRCT) and Mahidol University (N42A660380), and the Specific League Funds from Mahidol University.