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HESI ILSI Health and Environmental Sciences Institute HESI PROTEIN ALLERGENICITY TECHNICAL COMMITTEE Bioinformatics Expert Panel Workshop February 22 – 24, 2005 Mallorca, Spain Monograph Outline Chapter 1. Chapter Scope Food allergy review A. Prevalence B. Clinical manifestations C. Risks from conventional food supply Primary Author(s) Wesley Burks (Duke University Medical Center) 2. Review of the development of methodology for evaluating the human allergenic potential of novel proteins (Steve Taylor (Nebraska), Sue Hefle (Nebraska) Steve Taylor *† (Nebraska) A. Presentation of general approach for a typical bioinformatics comparison B. Risks from foods containing proteins introduced through biotechnology 3. Introduction to Bioinformatics Pinar Kondu*† IONTEK, INC., Istanbul, Turkey 4. Is there a minimum size constraint and number of sites for a protein to effectively cross-link IgE on mast cell/basophil receptors and induce mediator release? (Relevant for pepsin digestion as well as sequence/structural evaluations.) Edward F. Knol*† (University Medical Center Utrecht) 5. Evaluation of structural biology in the context of cross-reactivity Rob Aalberse*† Items to be addressed: Rob Aalberse and a second individual (Part 1) Heimo Breiteneder† (Austria) Clare Mills† 1. Minimum shared sequence identities indicating likely crossreactivity a. i. ii. iii. Serum IgE binding data Specificity Relative abundance Cross-reactivity determined by inhibition, not just direct binding 1 HESI ILSI Health and Environmental Sciences Institute Chapter Chapter Scope b. Evaluation of data relative to the FAO/WHO 2001 recommendation of 35% identity over >80 contiguous amino acids c. Evaluate food allergens and aeroallergens Primary Author(s) 2. Is either a short-segment amino acid matching programs or a structural comparison program better at predicting cross-reactivity than FASTA or BLASTP? Heimo Breiteneder and Clare Mills (Part 2) 1. Is there an example of allergic cross reactivity between nonhomologous proteins? a. b. Proteins sharing significant IgE cross-reactivity? If so, evidence of clinical significance? 2. Can cross-reactive conformational epitopes be predicted? a. By FASTA or BLASTP? b. By structural prediction algorithms? c. Is prediction restricted to highly homologous proteins or families? 6. 7. Review of available allergen databases. What were the criteria used to develop these particular databases? (historical discussion) Allergen database definitions Steve Gendel*† (US FDA NCFST) Evaluation of available IgE binding data and its utility in bioinformatics Gary Bannon*† (Monsanto) John Jenkins† – (Institute of Food Research UK) Tadashi Ogawa † (Kyoto University, Japan) 8. Utility and methods of allergen specific IgE testing in the diagnosis of food allergy (including binding and inhibition tests) Ronald van Ree*† Stefan Vieths 9. Serum IgE testing in the event of a positive match in the bioinformatics searches (Company, Pharmacia Diagnostics, Andrew Saxon-CA, Hugh Sampson-NY) 2 Lars Poulsen*† (Denmark) HESI ILSI Health and Environmental Sciences Institute Chapter 10. Chapter Scope Development of Executive Summary and Overall Recommendations Primary Author(s) Editorial Board: Rob Aalberse† Jim Astwood† Wesley Burks Sue Hefle† Greg Ladics† Sue MacIntosh† Hugh Sampson Steve Taylor† * Lead Author †Participation Confirmed 3