Abstract
MotivationDue to the risk of inducing an immediate Type I (IgE-mediated) allergic response, proteins intended for use in consumer products must be investigated for their allergenic potential before introduction into the marketplace. The FAO/WHO guidelines for computational assessment of allergenic potential of proteins based on short peptide hits and linear sequence window identity thresholds misclassify many proteins as allergens.ResultsWe developed AllerCatPro which predicts the allergenic potential of proteins based on similarity of their 3D protein structure as well as their amino acid sequence compared with a data set of known protein allergens comprising of 4180 unique allergenic protein sequences derived from the union of the major databases Food Allergy Research and Resource Program, Comprehensive Protein Allergen Resource, WHO/International Union of Immunological Societies, UniProtKB and Allergome. We extended the hexamer hit rule by removing peptides with high probability of random occurrence measured by sequence entropy as well as requiring 3 or more hexamer hits consistent with natural linear epitope patterns in known allergens. This is complemented with a Gluten-like repeat pattern detection. We also switched from a linear sequence window similarity to a B-cell epitope-like 3D surface similarity window which became possible through extensive 3D structure modeling covering the majority (74%) of allergens. In case no structure similarity is found, the decision workflow reverts to the old linear sequence window rule. The overall accuracy of AllerCatPro is 84% compared with other current methods which range from 51 to 73%. Both the FAO/WHO rules and AllerCatPro achieve highest sensitivity but AllerCatPro provides a 37-fold increase in specificity.Availability and implementation https://allercatpro.bii.a-star.edu.sg/ Supplementary information Supplementary data are available at Bioinformatics online.
Highlights
Protein allergens contain immunogenic and antigenic structures that can lead to an immunoglobulin (Ig) E-mediated respiratory (Type I)allergy
The current approach relies on the guidance of allergenicity assessment for genetically modified plant foods recommended by FAO/ WHO (2001), which is based on single hexamer peptide hits and sequence identity thresholds to known allergens
The UniProtKB, not specialized on allergens alone, is one of the most established sources for general protein annotations. It is based on a combination of manual curation and annotation by close similarity and uses the controlled keyword “Allergen” to attribute allergenic potential to proteins
Summary
Protein allergens contain immunogenic and antigenic structures that can lead to an immunoglobulin (Ig) E-mediated respiratory (Type I)allergy. The current approach relies on the guidance of allergenicity assessment for genetically modified plant foods recommended by FAO/ WHO (2001), which is based on single hexamer peptide hits and sequence identity thresholds to known allergens. This similarity approach leads to many wrongly classified proteins as potentially allergenic (Stadler and Stadler, 2003), including up to 90% of all human proteins (Supplementary Fig. S1)
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