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Evaluation of different generic in silico methods for predicting HLA class I binding peptide vaccine candidates using a reverse approach

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Abstract

Since CD8+ T cell response is crucial to combat intracellular infections and cancer, identification of class I HLA binding peptides is of immense clinical value. The experimental identification of such peptides is protracted and laborious. Exploiting in silico tools to discover such peptides is an attractive alternative. However, this approach needs a thorough assessment before its elaborate application. We have adopted a reverse approach to evaluate the reliability of eight different servers (inclusive of 55 predictors) by exploiting experimentally proven data. A comprehensive data set of more than 960 peptides was employed to test the efficacy of the programs. We have validated commonly used strategies to predict peptides that bind to seven most prevalent HLA class I alleles. We conclude that four of the eight servers are more adept in predictions. Although the overall predictions for class I MHC binders were superior to class II MHC binders, individual predictors for different alleles belonging to the same program were highly variable in their efficiencies. We have also addressed whether a consensus approach can yield better prediction efficiency. We observed that combining the results from different in silico programs could not increase the efficiency significantly.

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Abbreviations

HLA:

Human leukocyte antigen

MHC:

Major histocompatibility complex

SVM:

Support vector machine

ANN:

Artificial neural networks

References

  • Baldi P, Brunak S, Chauvin Y, Andersen CA et al (2000) Assessing the accuracy of prediction algorithms for classification: an overview. Bioinformatics 16:412–424

    Article  CAS  PubMed  Google Scholar 

  • Bhasin M, Raghava GP (2007) A hybrid approach for predicting promiscuous MHC class I restricted T cell epitopes. J Biosci 32:31–42

    Article  CAS  PubMed  Google Scholar 

  • Bui HH, Sidney J, Peters B, Sathiamurthy M, Sinichi A, Purton KA, Mothe BR, Chisari FV, Watkins DI, Sette A (2005) Automated generation and evaluation of specific MHC binding predictive tools: ARB matrix applications. Immunogenetics 57(5):304–314

    Article  CAS  PubMed  Google Scholar 

  • Burrows SR, Rossjohn J, McCluskey J (2006) Have we cut ourselves too short in mapping CTL epitopes? Trends Immunol 27:11–16

    Article  CAS  PubMed  Google Scholar 

  • Donnes P, Kohlbacher O (2006) SVMHC: a server for prediction of MHC-binding peptides. Nucleic Acids Res 34:W194–W197

    Article  PubMed  Google Scholar 

  • Garcia KC, Teyton L, Wilson IA (1999) Structural basis of T cell recognition. Annu Rev Immunol 17:369–397

    Article  CAS  PubMed  Google Scholar 

  • Gowthaman U, Agrewala JN (2008) In silico tools for predicting peptides binding to HLA-class II molecules: more confusion than conclusion. J Prot Res 7:154–163

    Article  CAS  Google Scholar 

  • Gowthaman U, Agrewala JN (2009) In silico methods for predicting T-cell epitopes: Dr Jekyll or Mr Hyde? Expert Rev Proteomics 6:527–537

    Article  CAS  PubMed  Google Scholar 

  • Harrison LC et al (1997) A peptide-binding motif for I-A(g7), the class II major histocompatibility complex (MHC) molecule of NOD and Biozzi AB/H mice. J Exp Med 185:1013–1021

    Article  CAS  PubMed  Google Scholar 

  • Hoof I, Peters B, Sidney J, Pedersen L, Sette A, Lund O, Buus S, Nielsen M (2009) NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics 61:1–13

    Article  CAS  PubMed  Google Scholar 

  • Lin HH, Ray S, Tongchusak S, Reinherz EL, Brusic V (2008) Evaluation of MHC class I peptide binding prediction servers: applications for vaccine research. BMC Immunol 9:8

    Article  PubMed  Google Scholar 

  • Lundegaard C, Lambert K, Harndah M, Buus S, Lund O, Nielsen M (2008) NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8–11. Nucleic Acids Res 36:W509–W512

    Article  CAS  PubMed  Google Scholar 

  • MacNamara A, Kadolsky U, Bangham CR, Asquith B (2009) T-cell epitope prediction: rescaling can mask biological variation between MHC molecules. PLoS Comput Biol 5:e1000327

    Article  PubMed  Google Scholar 

  • Parmiani G, De Filippo A, Novellino L, Castelli C (2007) Unique human tumor antigens: immunobiology and use in clinical trials. J Immunol 178:1975–1979

    CAS  PubMed  Google Scholar 

  • Peters B et al (2005) The immune epitope database and analysis resource: from vision to blueprint. PLoS Biol 3:e91

    Article  PubMed  Google Scholar 

  • Purcell AW, McCluskey J, Rossjohn J (2007) More than one reason to rethink the use of peptides in vaccine design. Nat Rev Drug Discov 6:404–414

    Article  CAS  PubMed  Google Scholar 

  • Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50(3–4):213–219

    Article  CAS  PubMed  Google Scholar 

  • Reche PA, Reinherz EL (2003) Sequence variability analysis of human class I and class II MHC molecules: functional and structural correlates of amino acid polymorphisms. J Mol Biol 331(3):623–641

    Article  CAS  PubMed  Google Scholar 

  • Reche PA, Glutting JP, Reinherz EL (2002) Prediction of MHC class I binding peptides using profile motifs. Human Immunol 63:701–709

    Article  CAS  Google Scholar 

  • Reche PA, Glutting JP, Zhang H, Reinherz EL (2004) Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles. Immunogenetics 56:405–419

    Article  CAS  PubMed  Google Scholar 

  • Robinson J et al (2009) The IMGT/HLA database. Nucleic Acids Res 37:D1013–D1017

    Article  CAS  PubMed  Google Scholar 

  • Stern LJ, Wiley DC (1994) Antigen peptide binding by class I and class II histocompatibility proteins. Structure 2:245–251

    Article  CAS  PubMed  Google Scholar 

  • Tong JC, Tan TW, Ranganathan S (2006) Methods and protocols for prediction of immunogenic epitopes. Brief Bioinform 8:96–108

    Article  PubMed  Google Scholar 

  • Topalian SL et al (1996) Melanoma-specific CD4+ T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes. J Exp Med 183:1965–1971

    Article  CAS  PubMed  Google Scholar 

  • Toseland CP, Clayton DJ, McSparron H, Hemsley SL, Blythe MJ, Paine K, Doytchinova IA, Guan P, Hattotuwagama CK, Flower DR (2005) AntiJen: a quantitative immunology database integrating functional, thermodynamic, kinetic, biophysical, and cellular data. Immunome Res 1(1):4

    Article  PubMed  Google Scholar 

  • Toseland CP, Clayton DJ, McSparron H, Hemsley SL, Blythe MJ, Paine K, Trost B, Bickis M, Kusalik A (2007) Strength in numbers: achieving greater accuracy in MHC-I binding prediction by combining the results from multiple prediction tools. Immunome Res 3:5

    Article  Google Scholar 

  • Wang P et al (2008) A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. PLoS Comput Biol 4:e1000048

    Article  PubMed  Google Scholar 

  • Zhang Q et al (2008) Immune epitope database analysis resource (IEDB-AR). Nucleic Acids Res 36:W513–W518

    Article  CAS  PubMed  Google Scholar 

  • Zinkernagel RM, Doherty PC (1974) Restriction of in vitro T-cell mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semi allogeneic system. Nature 248:701–702

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors are thankful to Dr. Balvinder Singh, Institute of Microbial Technology, Chandigarh for valuable suggestions and discussions and Priya Gowthaman for her help in manuscript preparation. UG is a recipient of Junior Research Fellowship of Department of Biotechnology. CSB is a recipient of Junior Research Fellowship of Council of Scientific and Industrial Research. The authors also wish to thank Department of Biotechnology and Council of Scientific and Industrial Research, India for financial support.

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The authors declare no conflict of interests.

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Correspondence to Javed N. Agrewala.

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U. Gowthaman and S. B. Chodisetti have contributed equally.

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726_2010_579_MOESM1_ESM.pdf

Variability in the prediction efficiency for different alleles in a single program. Matthew’s correlation coefficients for different alleles from a single program is depicted as bar diagrams for Rankpep (A), ComPred (B), NetMHC (C), NetMHCPan (D), ARB-Matrix (E), IEDB-ANN (F), SVMHC-SYFPEITHI (G), SVMHC-MHCPep (H) (PDF 33 kb)

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Gowthaman, U., Chodisetti, S.B., Parihar, P. et al. Evaluation of different generic in silico methods for predicting HLA class I binding peptide vaccine candidates using a reverse approach. Amino Acids 39, 1333–1342 (2010). https://doi.org/10.1007/s00726-010-0579-2

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