Bioinformatic methods for allergenicity assessment using a comprehensive allergen database.
BACKGROUND
A principal aim of the safety assessment of genetically modified crops is to prevent the introduction of known or clinically cross-reactive allergens. Current bioinformatic tools and a database of allergens and gliadins were tested for the ability to identify potential allergens by analyzing 6 Bacillus thuringiensis insecticidal proteins, 3 common non-allergenic food proteins and 50 randomly selected corn (Zea mays) proteins.


METHODS
Protein sequences were compared to allergens using the FASTA algorithm and by searching for matches of 6, 7 or 8 contiguous identical amino acids.


RESULTS
No significant sequence similarities or matches of 8 contiguous amino acids were found with the B. thuringiensis or food proteins. Surprisingly, 41 of 50 corn proteins matched at least one allergen with 6 contiguous identical amino acids. Only 7 of 50 corn proteins matched an allergen with 8 contiguous identical amino acids. When assessed for overall structural similarity to allergens, these 7 plus 2 additional corn proteins shared >or=35% identity in an overlap of >or=80 amino acids, but only 6 of the 7 were similar across the length of the protein, or shared >50% identity to an allergen.


CONCLUSIONS
An evaluation of a protein by the FASTA algorithm is the most predictive of a clinically relevant cross-reactive allergen. An additional search for matches of 8 amino acids may provide an added margin of safety when assessing the potential allergenicity of a protein, but a search with a 6-amino-acid window produces many random, irrelevant matches.
Hileman
Ronald E
RE
Monsanto Company, Product Safety Center, St. Louis, Mo., USA.
Silvanovich
Andre
A
Goodman
Richard E
RE
Rice
Elena A
EA
Holleschak
Gyula
G
Astwood
James D
JD
Hefle
Susan L
SL
D000465:Algorithms; D000485:Allergens / Q000235:genetics* / Q000276:immunology; D001413:Bacillus thuringiensis / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D019295:Computational Biology / Q000379:methods*; D003429:Cross Reactions; D030562:Databases, Protein; D005903:Gliadin / Q000235:genetics; D007073:Immunoglobulin E / Q000276:immunology; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology; D030821:Plants, Genetically Modified; D017386:Sequence Homology, Amino Acid; D003313:Zea mays / Q000276:immunology
D000485:Allergens; D001426:Bacterial Proteins; D010940:Plant Proteins; D007073:Immunoglobulin E; D005903:Gliadin