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In Silico Prediction of Linear B-Cell Epitopes on Proteins

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Prediction of Protein Secondary Structure

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1484))

Abstract

Antibody-protein interactions play a critical role in the humoral immune response. B-cells secrete antibodies, which bind antigens (e.g., cell surface proteins of pathogens). The specific parts of antigens that are recognized by antibodies are called B-cell epitopes. These epitopes can be linear, corresponding to a contiguous amino acid sequence fragment of an antigen, or conformational, in which residues critical for recognition may not be contiguous in the primary sequence, but are in close proximity within the folded protein 3D structure.

Identification of B-cell epitopes in target antigens is one of the key steps in epitope-driven subunit vaccine design, immunodiagnostic tests, and antibody production. In silico bioinformatics techniques offer a promising and cost-effective approach for identifying potential B-cell epitopes in a target vaccine candidate. In this chapter, we show how to utilize online B-cell epitope prediction tools to identify linear B-cell epitopes from the primary amino acid sequence of proteins.

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References

  1. Abbas AK, Lichtman AH, Pillai S (2014) Cellular and molecular immunology: with student consult online access. Elsevier Health Sciences, Philadelphia, PA

    Google Scholar 

  2. Abbott WM, Damschroder MM, Lowe DC (2014) Current approaches to fine mapping of antigen–antibody interactions. Immunology 142(4):526–535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Reineke U, Schutkowski M (2009) Epitope mapping protocols, vol 524, Methods in molecular biology. Humana Press, New York

    Google Scholar 

  4. EL-Manzalawy Y, Honavar V (2010) Recent advances in B-cell epitope prediction methods. Immunome Res Suppl 2:S2

    Article  Google Scholar 

  5. Walter G (1986) Production and use of antibodies against synthetic peptides. J Immunol Methods 88(2):149–161

    Article  CAS  PubMed  Google Scholar 

  6. Wu X, Li X, Zhang Q, Wulin S, Bai X, Zhang T, Wang Y, Liu M, Zhang Y (2015) Identification of a conserved B-cell epitope on duck hepatitis A type 1 virus VP1 protein. PLoS One 10(2):e0118041

    Article  PubMed  PubMed Central  Google Scholar 

  7. Palumbo E, Fiaschi L, Brunelli B, Marchi S, Savino S, Pizza M (2012) Antigen identification starting from the genome: a “Reverse Vaccinology” approach applied to MenB. In: Neisseria meningitidis: advanced methods and protocols. Methods in molecular biology, vol 799. Springer, pp 361–403

    Google Scholar 

  8. Donati C, Rappuoli R (2013) Reverse vaccinology in the 21st century: improvements over the original design. Ann N Y Acad Sci 1285(1):115–132

    Article  CAS  PubMed  Google Scholar 

  9. Xiang Z, He Y (2013) Genome-wide prediction of vaccine targets for human herpes simplex viruses using Vaxign reverse vaccinology. BMC Bioinformatics 14(Suppl 4):S2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Emini EA, Hughes JV, Perlow D, Boger J (1985) Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide. J Virol 55(3):836–839

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Karplus P, Schulz G (1985) Prediction of chain flexibility in proteins. Naturwissenschaften 72(4):212–213

    Article  CAS  Google Scholar 

  12. Parker J, Guo D, Hodges R (1986) 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. Biochemistry 25(19):5425–5432

    Article  CAS  PubMed  Google Scholar 

  13. Saha S, Raghava G (2004) BcePred: prediction of continuous B-cell epitopes in antigenic sequences using physico-chemical properties. In: Artificial immune systems. Lecture notes in computer science, vol 3239. Springer, pp 197–204

    Google Scholar 

  14. Larsen J, Lund O, Nielsen M (2006) Improved method for predicting linear B-cell epitopes. Immunome Res 2(2):1–7

    Google Scholar 

  15. EL-Manzalawy Y, Dobbs D, Honavar V (2008) Predicting linear B-cell epitopes using string kernels. J Mol Recognit 21(4):243–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. EL-Manzalawy Y, Dobbs D, Honavar V (2008) Predicting flexible length linear B-cell epitopes. In: Computational systems bioinformatics. NIH Public Access, pp 121–132

    Google Scholar 

  17. Sweredoski MJ, Baldi P (2009) COBEpro: a novel system for predicting continuous B-cell epitopes. Protein Eng Design Select 22(3):113–120

    Article  CAS  Google Scholar 

  18. Singh H, Ansari HR, Raghava GP (2013) Improved method for linear B-cell epitope prediction using Antigen’s primary sequence. PLoS One 8(5):e62216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. EL-Manzalawy Y, Honavar V (2014) Building classifier ensembles for B-cell epitope prediction. In: Immunoinformatics. Methods in molecular biology, vol 1184. Springer, pp 285–294

    Google Scholar 

  20. Esmaielbeiki R, Krawczyk K, Knapp B, Nebel J-C, Deane CM (2015) Progress and challenges in predicting protein interfaces. Brief Bioinformatics bbv027

    Google Scholar 

  21. Xue LC, Dobbs D, Bonvin A, Honavar V (2015) Protein-protein interface predictions by data-driven methods: a review. FEBS Lett 589(23):3516–3526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Yao B, Zheng D, Liang S, Zhang C (2013) Conformational B-cell epitope prediction on antigen protein structures: a review of current algorithms and comparison with common binding site prediction methods. PLoS One 8(4):e62249

    Google Scholar 

  23. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28(1):235–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gao J, Faraggi E, Zhou Y, Ruan J, Kurgan L (2012) BEST: improved prediction of B-cell epitopes from antigen sequences. PLoS One 7(6):e40104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ansari HR, Raghava G (2010) Identification of conformational B-cell epitopes in an antigen from its primary sequence. Immunome Res 6(6):1–9

    Google Scholar 

  26. Sela-Culang I, Ofran Y, Peters B (2015) Antibody specific epitope prediction—emergence of a new paradigm. Curr Opin Virol 11:98–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Xue LC, Dobbs D, Honavar V (2011) HomPPI: a class of sequence homology based protein-protein interface prediction methods. BMC Bioinformatics 12(1):244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Minhas A, ul Amir F, Geiss BJ, Ben‐Hur A (2014) PAIRpred: partner-specific prediction of interacting residues from sequence and structure. Proteins 82(7):1142–1155

    Article  PubMed  Google Scholar 

  29. El-Manzalawy Y, Dobbs D, Honavar V (2011) Predicting MHC-II binding affinity using multiple instance regression. Comput Biol Bioinformatics IEEE/ACM Trans 8(4):1067–1079

    Article  CAS  Google Scholar 

  30. Trolle T, Metushi IG, Greenbaum JA, Kim Y, Sidney J, Lund O, Sette A, Peters B, Nielsen M (2015) Automated benchmarking of peptide-MHC class I binding predictions. Bioinformatics btv123

    Google Scholar 

  31. Rubinstein ND, Mayrose I, Halperin D, Yekutieli D, Gershoni JM, Pupko T (2008) Computational characterization of B-cell epitopes. Mol Immunol 45(12):3477–3489

    Article  CAS  PubMed  Google Scholar 

  32. Chen J, Liu H, Yang J, Chou K-C (2007) Prediction of linear B-cell epitopes using amino acid pair antigenicity scale. Amino Acids 33(3):423–428

    Article  CAS  PubMed  Google Scholar 

  33. Zhang Q, Wang P, Kim Y, Haste-Andersen P, Beaver J, Bourne PE, Bui H-H, Buus S, Frankild S, Greenbaum J (2008) Immune epitope database analysis resource (IEDB-AR). Nucleic Acids Res 36(suppl 2):W513–W518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Krawczyk K, Liu X, Baker T, Shi J, Deane CM (2014) Improving B-cell epitope prediction and its application to global antibody-antigen docking. Bioinformatics 30(16):2288–2294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhao L, Li J (2010) Mining for the antibody-antigen interacting associations that predict the B cell epitopes. BMC Struct Biol 10(Suppl 1):S6

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zhao L, Wong L, Li J (2011) Antibody-specified B-cell epitope prediction in line with the principle of context-awareness. Comput Biol Bioinformatics IEEE/ACM Trans 8(6):1483–1494

    Article  CAS  Google Scholar 

  37. Sela-Culang I, Benhnia MR-E-I, Matho MH, Kaever T, Maybeno M, Schlossman A, Nimrod G, Li S, Xiang Y, Zajonc D (2014) Using a combined computational-experimental approach to predict antibody-specific B cell epitopes. Structure 22(4):646–657

    Article  CAS  PubMed  Google Scholar 

  38. Herraez A (2006) Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ 34(4):255–261

    Article  CAS  PubMed  Google Scholar 

  39. DeLano WL (2002) Pymol: an open-source molecular graphics tool. CCP4 Newslett Protein Crystallogr 40:82–92

    Google Scholar 

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Acknowledgments

This work was supported by NIH grant GM066387 to VGH and DD, by Edward Frymoyer Chair of Information Sciences and Technology at Pennsylvania State University to VGH, and by a Presidential Initiative for Interdisciplinary Research (PIIR) award from Iowa State University to DD.

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Correspondence to Vasant G. Honavar .

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EL-Manzalawy, Y., Dobbs, D., Honavar, V.G. (2017). In Silico Prediction of Linear B-Cell Epitopes on Proteins. In: Zhou, Y., Kloczkowski, A., Faraggi, E., Yang, Y. (eds) Prediction of Protein Secondary Structure. Methods in Molecular Biology, vol 1484. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6406-2_17

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  • DOI: https://doi.org/10.1007/978-1-4939-6406-2_17

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6404-8

  • Online ISBN: 978-1-4939-6406-2

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