Abstract

Identifying protein surface regions preferentially recognizable by antibodies (antigenic epitopes) is at the heart of new immuno-diagnostic reagent discovery and vaccine design, and computational methods for antigenic epitope prediction provide crucial means to serve this purpose. Many linear B-cell epitope prediction methods were developed, such as BepiPred, ABCPred, AAP, BCPred, BayesB, BEOracle/BROracle, and BEST, towards this goal. However, effective immunological research demands more robust performance of the prediction method than what the current algorithms could provide. In this work, a new method to predict linear antigenic epitopes is developed; Support Vector Machine has been utilized by combining the Tri-peptide similarity and Propensity scores (SVMTriP). Applied to non-redundant B-cell linear epitopes extracted from IEDB, SVMTriP achieves a sensitivity of 80.1% and a precision of 55.2% with a five-fold cross-validation. The AUC value is 0.702. The combination of similarity and propensity of tri-peptide subsequences can improve the prediction performance for linear B-cell epitopes. Moreover, SVMTriP is capable of recognizing viral peptides from a human protein sequence background. A web server based on our method is constructed for public use. The server and all datasets used in the current study are available at http://sysbio.unl.edu/SVMTriP.

Highlights

  • By secreting antibodies against antigens, B-cells play an important role in the immune system to fight an invasive pathogenic organism or substance

  • A continuous epitope is a consecutive fragment from the protein sequence; a discontinuous epitope is composed of several fragments scattered along the protein sequence, but still form an antigen-binding interface in 3D

  • The majority of available epitope prediction methods focus on continuous epitopes due to the relative simplicity of the problem and the convenience of available investigation methods, in which the amino acid sequence of a protein is taken as the input

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Summary

Introduction

By secreting antibodies against antigens, B-cells play an important role in the immune system to fight an invasive pathogenic organism or substance. The majority of available epitope prediction methods focus on continuous epitopes due to the relative simplicity of the problem and the convenience of available investigation methods, in which the amino acid sequence of a protein is taken as the input. Such prediction methods are based upon the amino acid properties including hydrophilicity [3,4], solvent accessibility [5], secondary structure [6], flexibility [7], and antigenicity [8]. Based on the epitope databases such as IEDB [9], Bcipep [10], and FIMM [11], there are some methods using machine learning approaches, such as Hidden Markov Model (HMM) [12], Artificial Neural Network (ANN) [13], and Support Vector Machine (SVM) [14,15], to locate linear epitopes, such as PREDITOP [8,16], PEOPLE [17], BEPITOPE [18], BepiPred [12], ABCPred [13], AAP [14], BCPred [15], BayesB [19], BEOracle/BROracle [20], and BEST [21]

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