Prediction of antigenic epitopes on protein surfaces by consensus scoring

BackgroundPrediction of antigenic epitopes on protein surfaces is important for vaccine design. Most existing epitope prediction methods focus on protein sequences to predict continuous epitopes linear in sequence. Only a few structure-based epitope prediction algorithms are available and they have not yet shown satisfying performance.ResultsWe present a new antigen Epitope Prediction method, which uses ConsEnsus Scoring (EPCES) from six different scoring functions - residue epitope propensity, conservation score, side-chain energy score, contact number, surface planarity score, and secondary structure composition. Applied to unbounded antigen structures from an independent test set, EPCES was able to predict antigenic eptitopes with 47.8% sensitivity, 69.5% specificity and an AUC value of 0.632. The performance of the method is statistically similar to other published methods. The AUC value of EPCES is slightly higher compared to the best results of existing algorithms by about 0.034.ConclusionOur work shows consensus scoring of multiple features has a better performance than any single term. The successful prediction is also due to the new score of residue epitope propensity based on atomic solvent accessibility.

[1]  Zhiping Weng,et al.  A protein–protein docking benchmark , 2003, Proteins.

[2]  S. Jones,et al.  Prediction of protein-protein interaction sites using patch analysis. , 1997, Journal of molecular biology.

[3]  Van Regenmortel MHV.  Mapping Epitope Structure and Activity: From One-Dimensional Prediction to Four-Dimensional Description of Antigenic Specificity , 1996, Methods.

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

[5]  Jian Huang,et al.  CED: a conformational epitope database , 2006, BMC Immunology.

[6]  Wei Li,et al.  ElliPro: a new structure-based tool for the prediction of antibody epitopes , 2008, BMC Bioinformatics.

[7]  Song Liu,et al.  Protein binding site prediction using an empirical scoring function , 2006, Nucleic acids research.

[8]  Huan-Xiang Zhou,et al.  Interaction-site prediction for protein complexes: a critical assessment , 2007, Bioinform..

[9]  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.

[10]  A. Giuliani,et al.  A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process , 2009, BMC Structural Biology.

[11]  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.

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

[13]  S. Jones,et al.  Analysis of protein-protein interaction sites using surface patches. , 1997, Journal of molecular biology.

[14]  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.

[15]  P. Y. Chou,et al.  Empirical predictions of protein conformation. , 1978, Annual review of biochemistry.

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

[17]  M. V. Regenmortel,et al.  Mapping Epitope Structure and Activity: From One-Dimensional Prediction to Four-Dimensional Description of Antigenic Specificity , 1996 .

[18]  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.

[19]  Z. Weng,et al.  Protein–protein docking benchmark 2.0: An update , 2005, Proteins.

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

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

[22]  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.

[23]  Salvador Eugenio C Caoili.  A structural-energetic basis for B-cell epitope prediction. , 2006, Protein and peptide letters.

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

[25]  Nimrod D. Rubinstein,et al.  A machine-learning approach for predicting B-cell epitopes. , 2009, Molecular immunology.

[26]  Urmila Kulkarni-Kale,et al.  CEP: a conformational epitope prediction server , 2005, Nucleic Acids Res..

[27]  Andrew C. R. Martin,et al.  SACS-Self-maintaining database of antibody crystal structure information , 2002, Bioinform..

[28]  Pierre Baldi,et al.  PEPITO: improved discontinuous B-cell epitope prediction using multiple distance thresholds and half sphere exposure , 2008, Bioinform..

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

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

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

[32]  Jian Zhang,et al.  Prediction of the interaction site on the surface of an isolated protein structure by analysis of side chain energy scores , 2004, Proteins.

[33]  Limsoon Wong,et al.  FIMM, a database of functional molecular immunology , 2000, Nucleic Acids Res..

[34]  Nick V Grishin,et al.  Effective scoring function for protein sequence design , 2003, Proteins.

[35]  P. Tongaonkar,et al.  A semi‐empirical method for prediction of antigenic determinants on protein antigens , 1990, FEBS letters.

[36]  Arno Lukas,et al.  Identification of discontinuous antigenic determinants on proteins based on shape complementarities , 2007, Journal of molecular recognition : JMR.

[37]  P. Karplus,et al.  Prediction of chain flexibility in proteins , 1985, Naturwissenschaften.