Improved method for predicting linear B-cell epitopes

BackgroundB-cell epitopes are the sites of molecules that are recognized by antibodies of the immune system. Knowledge of B-cell epitopes may be used in the design of vaccines and diagnostics tests. It is therefore of interest to develop improved methods for predicting B-cell epitopes. In this paper, we describe an improved method for predicting linear B-cell epitopes.ResultsIn order to do this, three data sets of linear B-cell epitope annotated proteins were constructed. A data set was collected from the literature, another data set was extracted from the AntiJen database and a data sets of epitopes in the proteins of HIV was collected from the Los Alamos HIV database. An unbiased validation of the methods was made by testing on data sets on which they were neither trained nor optimized on. We have measured the performance in a non-parametric way by constructing ROC-curves.ConclusionThe best single method for predicting linear B-cell epitopes is the hidden Markov model. Combining the hidden Markov model with one of the best propensity scale methods, we obtained the BepiPred method. When tested on the validation data set this method performs significantly better than any of the other methods tested. The server and data sets are publicly available at http://www.cbs.dtu.dk/services/BepiPred.

[1]  Ruurd van der Zee,et al.  Prediction of sequential antigenic regions in proteins , 1985, FEBS letters.

[2]  K. R. Woods,et al.  Prediction of protein antigenic determinants from amino acid sequences. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[4]  R. Porter,et al.  Synthetic peptides as antigens. , 1986, Ciba Foundation symposium.

[5]  John E. Freund,et al.  Probability and statistics for engineers , 1965 .

[6]  E Westhof,et al.  Correlation between the location of antigenic sites and the prediction of turns in proteins. , 1993, Immunology letters.

[7]  Denis Hochstrasser,et al.  A Totally Synthetic Polyoxime Malaria Vaccine Containing Plasmodium falciparum B Cell and Universal T Cell Epitopes Elicits Immune Responses in Volunteers of Diverse HLA Types1 , 2001, The Journal of Immunology.

[8]  Søren Brunak,et al.  Improved prediction of MHC class I and class II epitopes using a novel Gibbs sampling approach , 2004, Bioinform..

[9]  J. Hazes,et al.  The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. , 2000, Arthritis and rheumatism.

[10]  D. Flower,et al.  Benchmarking B cell epitope prediction: Underperformance of existing methods , 2005, Protein science : a publication of the Protein Society.

[11]  Irini A. Doytchinova,et al.  JenPep: A Novel Computational Information Resource for Immunobiology and Vaccinology , 2003, J. Chem. Inf. Comput. Sci..

[12]  C. Granier,et al.  Fine molecular analysis of the antigenicity of the Androctonus australis hector scorpion neurotoxin II: a new antigenic epitope disclosed by the Pepscan method. , 1993, Molecular immunology.

[13]  M. Levitt Conformational preferences of amino acids in globular proteins. , 1978, Biochemistry.

[14]  J A Swets,et al.  Measuring the accuracy of diagnostic systems. , 1988, Science.

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

[16]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence data bank and its supplement TrEMBL , 1997, Nucleic Acids Res..

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

[18]  S. Henikoff,et al.  Amino acid substitution matrices from protein blocks. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  R. Hodges,et al.  New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites. , 1986, Biochemistry.

[20]  C. DeLisi,et al.  Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins. , 1987, Journal of molecular biology.

[21]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000 , 2000, Nucleic Acids Res..

[22]  E. Emini,et al.  Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide , 1985, Journal of virology.

[23]  E E Hughes,et al.  Ability of synthetic peptides representing epitopes of outer membrane protein F of Pseudomonas aeruginosa to afford protection against P. aeruginosa infection in a murine acute pneumonia model. , 1995, Vaccine.

[24]  Steve Wilson,et al.  The Immune Epitope Database and Analysis Resource: From Vision to Blueprint , 2005, PLoS biology.

[25]  E Westhof,et al.  Predicting location of continuous epitopes in proteins from their primary structures. , 1991, Methods in enzymology.

[26]  Ole Lund,et al.  Immunological Bioinformatics (Computational Molecular Biology) , 2005 .

[27]  P. Y. Chou,et al.  Prediction of the secondary structure of proteins from their amino acid sequence. , 2006 .