In the proposed work, we will develop software tools to predict T- and B-cell epitopes of allergenic and viral proteins. The approach is based on novel quantitative descriptors of the physical-chemical properties of amino acids developed recently by our group. The primary goal of the new approach is to use a minimal number of variables to establish the classification procedures and QSAR models. The novel descriptors of physical-chemical properties of amino acids will be used in combination with a partial least squares approach to reduce the number of variables in the discriminant analysis and in artificial neural networks. Algorithms based on multivariate classification, K-nearest-neighbor methods, support vector machines and neural networks will be developed and assessed by cross-validation for their ability to predict T- and B-cell epitopes in proteins. The resulting QSAR models/database approach can then be used to identify immunogenic epitopes in the proteins of pathogens for vaccine development and drug design. IgE epitopes, archived in our web-based, relational Structural Database of Allergenic Proteins (SDAP), will be used to develop the Bcell epitope prediction methods. Stereochemical variability plots will also be used to predict functional and immunological determinants on proteins from Dengue virus (DV). This information can aid in the design of vaccines that better stimulate neutralizing T- and B-cell responses to diverse variants of DV. The validated suite of software tools to identify and classify immunogenic peptides will be made available to the scientific community as a Web server, similar to SDAP. Collaborations with experimental groups will enable the practical applications of the tools, which include predicting the allergenicity of novel foods and drugs, improving specific immunotherapies for allergy and asthma, and vaccine design.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI064913-05
Application #
7570061
Study Section
Special Emphasis Panel (ZRG1-BDMA (01))
Program Officer
Gondre-Lewis, Timothy A
Project Start
2005-02-01
Project End
2011-07-31
Budget Start
2009-02-01
Budget End
2011-07-31
Support Year
5
Fiscal Year
2009
Total Cost
$280,910
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Bowen, David M; Lewis, Jessica A; Lu, Wenzhe et al. (2012) Simplifying complex sequence information: a PCP-consensus protein binds antibodies against all four Dengue serotypes. Vaccine 30:6081-7
Schein, Catherine H; Bowen, David M; Lewis, Jessica A et al. (2012) Physicochemical property consensus sequences for functional analysis, design of multivalent antigens and targeted antivirals. BMC Bioinformatics 13 Suppl 13:S9
Lu, Wenzhe; Negi, Surendra S; Oberhauser, Andres F et al. (2012) Engineering proteins with enhanced mechanical stability by force-specific sequence motifs. Proteins 80:1308-15
Tiwari, Ruby; Negi, Surendra S; Braun, Benjamin et al. (2012) Validation of a phage display and computational algorithm by mapping a conformational epitope of Bla g 2. Int Arch Allergy Immunol 157:323-30
Maleki, S J; Teuber, S S; Cheng, H et al. (2011) Computationally predicted IgE epitopes of walnut allergens contribute to cross-reactivity with peanuts. Allergy 66:1522-9
Ivanciuc, Ovidiu; Gendel, Steven M; Power, Trevor D et al. (2011) AllerML: markup language for allergens. Regul Toxicol Pharmacol 60:151-60
Danecek, Petr; Lu, Wenzhe; Schein, Catherine H (2010) PCP consensus sequences of flaviviruses: correlating variance with vector competence and disease phenotype. J Mol Biol 396:550-63
Danecek, Petr; Schein, Catherine H (2010) Flavitrack analysis of the structure and function of West Nile non-structural proteins. Int J Bioinform Res Appl 6:134-46
Schein, Catherine H; Oezguen, Numan; van der Heden van Noort, Gerbrand J et al. (2010) NMR solution structure of poliovirus uridylyated peptide linked to the genome (VPgpU). Peptides 31:1441-8
Schein, Catherine H; Ivanciuc, Ovidiu; Midoro-Horiuti, Terumi et al. (2010) An Allergen Portrait Gallery: Representative Structures and an Overview of IgE Binding Surfaces. Bioinform Biol Insights 4:113-25

Showing the most recent 10 out of 24 publications