Q-X1-P-X2 motif search for potential celiac disease risk has poor selectivity

The European Food Safety Authority (EFSA) recently published guidelines for assessment of potential celiac disease risk for newly expressed proteins in genetically modified (GM) crops. This novel step-wise approach prescribes, in part, how to conduct sequence identity searches between a newly expressed protein and known celiac disease peptides including a Q/E-X1-P-X2 amino acid motif. To evaluate the specificity of the recommended sequence identity searches in the context of risk assessment, protein sequences from celiac disease causing crops, as well as from crops not associated with celiac disease, were compared with known HLA-DQ restricted epitopes and searched for the presence of motifs followed by peptide analysis. Searches for the presence of the Q/E-X1-P-X2-motif were found to generate a high proportion of false-positive hits irrelevant to celiac disease risk. Identification of a 9mer exact match between a newly expressed protein and the known celiac disease peptides (recommended by the guideline) along with a supplementary sequence comparisons (suggested by FARRP/AllergenOnline) is considered better suited to more specifically capture the potential risk of a newly expressed protein for celiac disease.