Prediction of B-cell Linear Epitopes with a Combination of Support Vector Machine Classification and Amino Acid Propensity Identification

Epitopes are antigenic determinants that are useful because they induce B-cell antibody production and stimulate T-cell activation. Bioinformatics can enable rapid, efficient prediction of potential epitopes. Here, we designed a novel B-cell linear epitope prediction system called LEPS, Linear Epitope Prediction by Propensities and Support Vector Machine, that combined physico-chemical propensity identification and support vector machine (SVM) classification. We tested the LEPS on four datasets: AntiJen, HIV, a newly generated PC, and AHP, a combination of these three datasets. Peptides with globally or locally high physicochemical propensities were first identified as primitive linear epitope (LE) candidates. Then, candidates were classified with the SVM based on the unique features of amino acid segments. This reduced the number of predicted epitopes and enhanced the positive prediction value (PPV). Compared to four other well-known LE prediction systems, the LEPS achieved the highest accuracy (72.52%), specificity (84.22%), PPV (32.07%), and Matthews' correlation coefficient (10.36%).

[1]  W H Woolley,et al.  Theoretical biology and biophysics , 1971 .

[2]  J. Thornton,et al.  Continuous and discontinuous protein antigenic determinants , 1986, Nature.

[3]  D. Benjamin,et al.  B-cell epitopes: fact and fiction. , 1995, Advances in experimental medicine and biology.

[4]  J. Lieberman,et al.  Prediction of HIV peptide epitopes by a novel algorithm. , 1996, AIDS research and human retroviruses.

[5]  G. Cohen,et al.  Interactions of protein antigens with antibodies. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Helm,et al.  Mapping and mutational analysis of the IgE-binding epitopes on Ara h 1, a legume vicilin protein and a major allergen in peanut hypersensitivity. , 1997, European journal of biochemistry.

[7]  A. Alix,et al.  Predictive estimation of protein linear epitopes by using the program PEOPLE. , 1999, Vaccine.

[8]  S. Henri,et al.  Identification of a candidate vaccine peptide on the 37 kDa Schistosoma mansoni GAPDH. , 2000, Vaccine.

[9]  M. S. McClain,et al.  Antigenic Diversity among Helicobacter pyloriVacuolating Toxins , 2001, Infection and Immunity.

[10]  Jean-Luc Pellequer,et al.  BEPITOPE: predicting the location of continuous epitopes and patterns in proteins , 2003, Journal of molecular recognition : JMR.

[11]  Maria Jesus Martin,et al.  The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003 , 2003, Nucleic Acids Res..

[12]  Russell Schwartz,et al.  Epitope prediction algorithms for peptide-based vaccine design , 2003, Computational Systems Bioinformatics. CSB2003. Proceedings of the 2003 IEEE Bioinformatics Conference. CSB2003.

[13]  H. Budka,et al.  Antigenic profile of human recombinant PrP: generation and characterization of a versatile polyclonal antiserum , 2004, Journal of Neuroimmunology.

[14]  Gajendra P. S. Raghava,et al.  BcePred: Prediction of Continuous B-Cell Epitopes in Antigenic Sequences Using Physico-chemical Properties , 2004, ICARIS.

[15]  M. Bhasin,et al.  Bcipep: A database of B-cell epitopes , 2005, BMC Genomics.

[16]  Channa K. Hattotuwagama,et al.  AntiJen: a quantitative immunology database integrating functional, thermodynamic, kinetic, biophysical, and cellular data , 2005, Immunome research.

[17]  Chuan Yi Tang,et al.  A reinforced merging methodology for mapping unique peptide motifs in members of protein families , 2006, BMC Bioinformatics.

[18]  Morten Nielsen,et al.  Improved method for predicting linear B-cell epitopes , 2006, Immunome research.

[19]  Chi-Ju Chen,et al.  Immunological characterizations of the nucleocapsid protein based SARS vaccine candidates , 2006, Vaccine.

[20]  Marc H V Van Regenmortel,et al.  Immunoinformatics may lead to a reappraisal of the nature of B cell epitopes and of the feasibility of synthetic peptide vaccines , 2006, Journal of molecular recognition : JMR.

[21]  K. Chou,et al.  Prediction of linear B-cell epitopes using amino acid pair antigenicity scale , 2007, Amino Acids.

[22]  Sudipto Saha,et al.  Prediction of continuous B‐cell epitopes in an antigen using recurrent neural network , 2006, Proteins.

[23]  Irini A. Doytchinova,et al.  BMC Bioinformatics BioMed Central Methodology article VaxiJen: a server for prediction of protective antigens, tumour , 2007 .

[24]  Tun-Wen Pai,et al.  REMUS: a tool for identification of unique peptide segments as epitopes , 2006, Nucleic Acids Res..

[25]  O. Lund,et al.  Prediction of residues in discontinuous B‐cell epitopes using protein 3D structures , 2006, Protein science : a publication of the Protein Society.

[26]  Avner Schlessinger,et al.  Towards a consensus on datasets and evaluation metrics for developing B‐cell epitope prediction tools , 2007, Journal of molecular recognition : JMR.

[27]  Vasant Honavar,et al.  Predicting flexible length linear B-cell epitopes. , 2008, Computational systems bioinformatics. Computational Systems Bioinformatics Conference.

[28]  Tun-Wen Pai,et al.  Estimation and extraction of B‐cell linear epitopes predicted by mathematical morphology approaches , 2008, Journal of molecular recognition : JMR.

[29]  Vasant G Honavar,et al.  Predicting linear B‐cell epitopes using string kernels , 2008, Journal of molecular recognition : JMR.

[30]  T. Waterboer,et al.  Identification of B-Cell Epitopes on Virus-Like Particles of Cutaneous Alpha-Human Papillomaviruses , 2009, Journal of Virology.

[31]  E. Nascimento,et al.  Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3) , 2009, PloS one.

[32]  N. Mantis,et al.  Neutralizing Monoclonal Antibodies Directed against Defined Linear Epitopes on Domain 4 of Anthrax Protective Antigen , 2009, Infection and Immunity.

[33]  Jun Chen,et al.  HSP27: mechanisms of cellular protection against neuronal injury. , 2009, Current molecular medicine.

[34]  María Martín,et al.  The Universal Protein Resource (UniProt) in 2010 , 2010 .

[35]  F. Molinia,et al.  Identification and evaluation of an infertility-associated ZP3 epitope from the marsupial brushtail possum (Trichosurus vulpecula). , 2010, Vaccine.

[36]  Baris E. Suzek,et al.  The Universal Protein Resource (UniProt) in 2010 , 2009, Nucleic Acids Res..

[37]  R. Jia,et al.  Expression and characterization of recombinant VP19c protein and N-terminal from duck enteritis virus , 2011, Virology Journal.

[38]  P. Boisguérin,et al.  Identification of a Linear Epitope in Sortilin That Partakes in Pro-neurotrophin Binding* , 2010, The Journal of Biological Chemistry.

[39]  N. Cirillo,et al.  Controversial Role of Antibodies against Linear Epitopes of Desmoglein 3 in Pemphigus Vulgaris, as Revealed by Semiquantitative Living Cell Immunofluorescence Microscopy and in-Cell Elisa , 2010, International journal of immunopathology and pharmacology.

[40]  Matthias Mueller,et al.  Antigenic Characterization of Recombinant Hemagglutinin Proteins Derived from Different Avian Influenza Virus Subtypes , 2010, PloS one.

[41]  S. Caoili Benchmarking B-Cell Epitope Prediction for the Design of Peptide-Based Vaccines: Problems and Prospects , 2010, Journal of biomedicine & biotechnology.

[42]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[43]  Eva Liebau,et al.  Identification of major antigenic peptide of filarial glutathione-S-transferase. , 2011, Vaccine.