Prediction Model of MHC Class-II Binding Peptide Motifs Using Sequence Weighting Method for Vaccine Design

Identification of MHC class-II restricted epitope is an important goal in peptide based vaccine and diagnostic development. Currently, immuno informatics can circumvent conventional time-consuming and laborious experimental techniques of overlapping peptides from protein to epitope identification. However, prediction of MHC class-II epitope is difficult due to variable length of binding peptides (13-25 amino acids). In the present study, we applied the Gibbs motif sampler, Sturniolo pocket profile and NNAlign method for binding motif identification and further position specific scoring matrices (PSSM) using sequence weighting schemes for the prediction of peptide binding to seven human MHC class-II molecules. Here, we used a non-parametric performance measure, area under receiver operating characteristic curve (Aroc) which provides a global assessment of predictive power. The average prediction performances for motif identification based on NNAlign, Sturniolo pocket profile and Gibbs sampler in term of Aroc are 0.71, 0.68 and 0.64, respectively. Further improvements in the performance of MHC class-II binding peptide predictor largely depends on the size of training dataset, optimization of training parameters and the correct identification of the peptide binding motifs.

[1]  R. Rappuoli,et al.  Reverse vaccinology. , 2000, Current opinion in microbiology.

[2]  Vladimir Brusic,et al.  Dana-Farber repository for machine learning in immunology. , 2011, Journal of immunological methods.

[3]  M F del Guercio,et al.  Several common HLA-DR types share largely overlapping peptide binding repertoires. , 1998, Journal of immunology.

[4]  Morten Nielsen,et al.  NNAlign: A Web-Based Prediction Method Allowing Non-Expert End-User Discovery of Sequence Motifs in Quantitative Peptide Data , 2011, PloS one.

[5]  Maria V. Tejada-Simon,et al.  Naturally Processed HLA Class II Peptides Reveal Highly Conserved Immunogenic Flanking Region Sequence Preferences That Reflect Antigen Processing Rather Than Peptide-MHC Interactions1 , 2001, The Journal of Immunology.

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

[7]  Don C. Wiley,et al.  Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide , 1994, Nature.

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

[9]  Feroz Khan,et al.  Computational characterization of Plasmodium falciparum proteomic data for screening of potential vaccine candidates. , 2010, Human immunology.

[10]  U. Şahin,et al.  Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices , 1999, Nature Biotechnology.

[11]  Darren R Flower,et al.  Immunoinformatics and the in silico prediction of immunogenicity. An introduction. , 2007, Methods in molecular biology.

[12]  Vladimir Brusic,et al.  Evaluation of MHC-II peptide binding prediction servers: applications for vaccine research , 2008, BMC Bioinformatics.

[13]  R. Rappuoli,et al.  Designing the next generation of vaccines for global public health. , 2011, Omics : a journal of integrative biology.

[14]  P. Cresswell,et al.  Assembly, transport, and function of MHC class II molecules. , 1994, Annual review of immunology.

[15]  Darren R Flower,et al.  Immunoinformatics and the prediction of immunogenicity. , 2002, Applied bioinformatics.

[16]  Fang Chen,et al.  VIOLIN: vaccine investigation and online information network , 2007, Nucleic Acids Res..