Grantee Research Project Results
2013 Progress Report: Prediction of Allergenicity by Linear and Conformational Epitopes
EPA Grant Number: R834823Title: Prediction of Allergenicity by Linear and Conformational Epitopes
Investigators: Braun, Werner , Schein, Catherine H. , Ivanciuc, Ovidiu I
Institution: The University of Texas Medical Branch - Galveston
EPA Project Officer: Aja, Hayley
Project Period: September 15, 2010 through September 30, 2014
Project Period Covered by this Report: September 15, 2012 through September 14,2013
Project Amount: $425,000
RFA: Approaches to Assessing Potential Food Allergy from Genetically Engineered Plants (2009) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
The overall goal of this project is to provide quantitative bioinformatics criteria to determine the potential allergenicity of transgenic proteins in food products and plant-incorporated pesticides (PIP) from allergen specific motifs. The specific aims of the projects were three-fold:
Aim 1: to maintain and expand the currently available information in our Structural Database of Allergenic Proteins (SDAP) on the sequences, 3D structures and IgE epitopes of allergens.
Aim 2: to establish a database of allergen-specific motifs that can be quantitatively screened to estimate the potential allergenicity of a query protein sequence. A major effort in pursuing Aim 2 is the experimental validation of the computational tools in SDAP.
Aim 3: Develop novel computational methods to detect similar conformational epitopes.
Progress Summary:
A new feature of the SDAP website is the installation of a secure https port (https://fermi.utmb.edu/SDAP). This port allows users to access the SDAP website over a secure connection that prevents potential interception of the information by third parties. Specifically, it guarantees that the user of SDAP will communicate with a trusted website as certified from a well-established authority by a digital certificate. We considerably expanded the list of 3D-models of allergens in SDAP and demonstrated the high quality of the 3D models by comparing our 3D models to experimental 3D structures that were determined after our models were published. We also further refined our new computational methods for detecting allergen-specific motifs. Allergen-specific motifs are defined as short linear sequences that are common to many related known allergens. They provide an alternative way to predict IgE cross-reactivity. We defined those motifs for all major protein families with allergens and showed that these motifs can distinguish allergens in a protein family from non-allergenic members. Our new approach for 3D search of structural similar regions of allergens were further tested for specificity and sensitivity of the computational approach.
Future Activities:
- We will continue updating the SDAP database with novel allergens and 3D models.
- We have established new allergen-specific sequence motifs for major protein families. The computational cross validation of these motifs has been done. We now will test the validity of our motif search method with experimental data and publish the results.
- As several new X-ray crystal structures of allergens now are available with known IgE allergens, we can extend the test set for assessing the quality of our new 3D search method.
Journal Articles on this Report : 5 Displayed | Download in RIS Format
Other project views: | All 19 publications | 6 publications in selected types | All 6 journal articles |
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Ivanciuc O, Gendel SM, Power TD, Schein CH, Braun W. AllerML: markup language for allergens. Regulatory Toxicology and Pharmacology 2011;60(1):151-160. |
R834823 (2011) R834823 (2013) R834823 (Final) R834066 (Final) |
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Nesbit JB, Hurlburt BK, Schein CH, Cheng H, Wei H, Maleki SJ. Ara h 1 structure is retained after roasting and is important for enhanced binding to IgE. Molecular Nutrition and Food Research 2012;56(11):1739-1747. |
R834823 (2012) R834823 (2013) R834823 (Final) R834066 (Final) |
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Power TD, Ivanciuc O, Schein CH, Braun W. Assessment of 3D models for allergen research. Proteins 2013;81(4):545-554. |
R834823 (2012) R834823 (2013) R834823 (Final) |
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Schein CH, Bowen DM, Lewis JA, Choi K, Paul A, van der Heden van Noort GJ, Lu W, Filippov DV. Physicochemical property consensus sequences for functional analysis, design of multivalent antigens and targeted antivirals. BMC Bioinformatics 2012;13(Suppl 13):S9. |
R834823 (2012) R834823 (2013) R834823 (Final) R834066 (Final) |
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Tiwari R, Negi SS, Braun B, Braun W, Pomes A, Chapman MD, Goldblum RM, Midoro-Horiuti T. Validation of a phage display and computational algorithm by mapping a conformational epitope of Bla g 2. International Archives of Allergy and Immunology 2012;157(4):323-330. |
R834823 (2012) R834823 (2013) R834823 (Final) R833137 (Final) |
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Supplemental Keywords:
relational database, large scale 3D modeling of proteins, WHO/EFSA recommendations for risk assessment of proteinsRelevant Websites:
Home page of the Structural Database of Allergenic Proteins (SDAP): https://fermi.utmb.edu/SDAP/ Exit
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.