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Prediction of Linear and Conformational B-cell Epitopes

Prediction of Linear and Conformational B-cell Epitopes. Dr. G P S Raghava, Head Bioinformatics Centre Institute of Microbial Technology, Chandigarh, India. Web Site: http://www.imtech.res.in/raghava/. Whole Organism. Subunit Vaccines. Passive Immunization. Living vaccines Annutated

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Prediction of Linear and Conformational B-cell Epitopes

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  1. Prediction of Linear and Conformational B-cell Epitopes Dr. G P S Raghava, Head Bioinformatics Centre Institute of Microbial Technology, Chandigarh, India Web Site: http://www.imtech.res.in/raghava/

  2. Whole Organism Subunit Vaccines Passive Immunization • Living vaccines • Annutated • Killed organism • Polysaccharides • Toxoids • Recombinant Vaccine Delivery Type of Vaccines • Adjuvants • Edible Vaccine Non-Specific Immunotherapy Epitope based Vaccines Genetic Vaccines

  3. Strategies of vaccine development WHOLE ORGANISM Epitopes (Subunit Vaccine) Purified Antigen Protein/Oligosaccharide Attenuated/Killed B-cell, T-cell epitopes

  4. Adaptive Immunity Protective Antigens Vaccine Informatics Bioinformatics Centre Disease Causing Agents Innate Immunity IMTECH, Chandigarh Vaccine Delivery Pathogens/Invaders

  5. Types of epitopes B cell Epitope Conformational Linear B cell Epitope T cell Epitope Non- Conformational CTL epitope Class I MHCs Endogenous Antigen Processing Helper T cell epitope Class II MHCs Exogenous Antigen Processing

  6. Linear B-cell epitope prediction • Linear B-cell epitopes are as important or even more • applicative than conformational epitopes. • Most of the existing methods for linear B-cell epitopes are • based on old and very small dataset (~1000 epitopes). • Performance of all the methods are not better than 0.75 AUC. • None of the methods used experimentally verified negative • datasets.

  7. Adaptive Immunity Protective Antigens Vaccine Informatics Bioinformatics Centre Innate Immunity IMTECH, Chandigarh Vaccine Delivery BCIPEP: A database of B-cell epitopes. Saha et al.(2005) BMC Genomics 6:79. Saha et al. (2006) NAR (Online)

  8. BCEpred: Benchmarking of physico-cemical properties used in existing B-cell epitope prediction methods In 2003, we evaluate parmeters on 1029 non-redudant B-cell epitopes obtained from BCIpep and 1029 random peptide Saha and Raghava (2004) ICARIS 197-204.

  9. Challenge in Developing Method Machine learnning technique needs fixed length pattern where epitope have variable length Classification methods need positive and negative dataset There are experimentally proved B-cell epitopes (positive) dataset but not Non-epitopes (negative) ABCpred: ANN based method for B-cell epitope prediction Assumptions to fix the Problem More than 90% epitope have less than 20 residue so we fix maximum length 20 We added residues at both end of small epitopes from source protein to make length of epitope 20 We generate random peptides from proteins and used them as non-epitopes

  10. Creation of fixed pattern of 20 from epitopes

  11. Adaptive Immunity Protective Antigens Vaccine Informatics Bioinformatics Centre Innate Immunity IMTECH, Chandigarh Vaccine Delivery Prediction of B-Cell Epitopes • BCEpred: Prediction of Continuous B-cell epitopes • Benchmarking of existing methods • Evaluation of Physico-chemical properties • Poor performance slightly better than random • Combine all properties and achieve accuracy around 58% • Saha and Raghava (2004) ICARIS 197-204. • ABCpred: ANN based method for B-cell epitope prediction • Extract all epitopes from BCIPEP (around 2400) • 700 non-redundant epitopes used for testing and training • Recurrent neural network • Accuracy 66% achieved • Saha and Raghava (2006) Proteins,65:40-48 • ALGpred: Mapping and Prediction of Allergenic Epitopes • Allergenic proteins • IgE epitope and mapping • Saha and Raghava (2006) Nucleic Acids Research 34:W202-W209

  12. B-cell epitope classification B-cell epitope – structural feature of a molecule or pathogen, accessible and recognizable by B-cells Linear epitopes One segment of the amino acid chain Discontinuous epitope (with linear determinant) Discontinuous epitope Several small segments brought into proximity by the protein fold

  13. 3D Structure Sequence??

  14. Data collection and processing Immune Epitope Database (365 sequences) Ponomarenkoet al 2007 (161) Antigenic sequences with conformational B-cell epitope information 526 CD-HIT 40% 187 + - 2261 antibody interacting residues 107414 antibody non-interacting residues Feature Extraction Training and model generation

  15. Polar and charged residues are preferred in antibody interaction

  16. Propensities of surface-exposed and buried residues 2 sample Logo

  17. Pattern Generation Composition profile Binary profile Physico-chemical profile

  18. Comparison of structure based and CBTOPE algorithm on Benchmark dataset* *Ponomarenko et al 2007, BMC Structural Biology PPV - positive predictive value

  19. http://www.imtech.res.in/raghava/cbtope/submit.php

  20. B-cell epitope prediction related resources Rev. Med. Virol. 2009, 19: 77–96.

  21. . Epitope Mapping Using Phage Display Peptides

  22. Linear B-Cell Epitope Tools

  23. Conformational B-Cell Epitope Tools

  24. Thanks for your attention

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