Proteomic and Bioinformatic Analyses for the Identification of Proteins With Low Allergenic Potential for Hazard Assessment

Krutz, Nora L; Winget, Jason M.; Ryan, Cindy A.; Wimalasena, Rohan; Maurer‐Stroh, Sebastian; Dearman, Rebecca J.; Kimber, Ian; Gerberick, G. Frank

doi:10.1093/toxsci/kfz078

Cited by 17 publications

(20 citation statements)

References 38 publications

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“…Previous work using 50,090 protein sequences from maize found the sliding-window bioinformatic approach to falsely implicate 19.9% of putative non-allergens as allergens, while the 1:1 FASTA approach falsely implicated 7.5% of proteins. 16 Using the 125 high-abundance nonallergens from food crops 15 , false-positive rates were found to be 8.8% for the sliding-window approach and 0.8% for the 1:1 FASTA approach. The 8-amino acid exact match criterion falsely implicated 2.4% of the 125 high-abundance foodcrop proteins and the celiac-peptide-motif search incorrectly found 10.4% of the 125 non-allergenic proteins to represent a celiac-disease risk (only 1 of which originated from a crop known to cause celiac symptoms, wheat, but with no reports of this peptide causing celiac disease).…”

Section: Resultsmentioning

confidence: 99%

“…The 178 UniRef90 Cluster IDs listed in Table 4 of Krutz et al 15 , were used to search the UniProt database to obtain an amino acid sequence for each protein. Of these sequences, 169 returned current entries, and of those, 125 indicated the same source organism as listed in Table 4 of Krutz et al The amino acid sequences for these 125 high-abundance nonallergens were compared with the allergen sequences in the COMPARE database version 2019 (http://db.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, a list of abundant food proteins with low allergenic potential (hereafter referred to as non-allergens) was published along with the methods used to determine their abundance and status as non-allergens. 15 This list can now be used to better assess the false-positive rates for different bioinformatic algorithms designed to selectively detect allergenic risk. Here we used this list of abundant non-allergenic food proteins to assess the false-positive rates for the official criteria of >35% identity over an 80-mer sliding-window and an 8-mer exact-match, and a previously reported 1:1 FASTA similarity approach.…”

Section: Introductionmentioning

confidence: 99%

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Allergen false-detection using official bioinformatic algorithms

Herman

Song

2020

GM Crops & Food

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Bioinformatic amino acid sequence searches are used, in part, to assess the potential allergenic risk of newly expressed proteins in genetically engineered crops. Previous work has demonstrated that the searches required by government regulatory agencies falsely implicate many proteins from rarely allergenic crops as an allergenic risk. However, many proteins are found in crops at concentrations that may be insufficient to cause allergy. Here we used a recently developed set of high-abundance non-allergenic proteins to determine the false-positive rates for several algorithms required by regulatory bodies, and also for an alternative 1:1 FASTA approach previously found to be equally sensitive to the official sliding-window method, but far more selective. The current investigation confirms these earlier findings while addressing dietary exposure.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Allergen false-detection using official bioinformatic algorithms

Herman

Song

2020

GM Crops & Food

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“…They take into account, not only the sequence identity, but also the presence of characteristic motifs on the protein surface, such as B, T and IgE epitopes, the hydrophobic residues or structural similarity regions (Ivanciuc, Schein, and Braun 2003;). These techniques help predicting cross-reactivity between allergens, though they have also been used for the identification of proteins with low allergenic potential in novel foods, which can be used for the development and validation of methods to assess proteins with allergenic potential (Krutz et al 2019).…”

Section: Bioinformaticsmentioning

confidence: 99%

New applications of advanced instrumental techniques for the characterization of food allergenic proteins

Benedé

Lozano‐Ojalvo

Cristóbal

et al. 2021

Critical Reviews in Food Science and Nutrition

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Current approaches based on electrophoretic, chromatographic or immunochemical principles have allowed characterizing multiple allergens, mapping their epitopes, studying their mechanisms of action, developing detection and diagnostic methods and therapeutic strategies for the food and pharmaceutical industry. However, some of the common structural features related to the allergenic potential of food proteins remain unknown, or the pathological mechanism of food allergy is not yet fully understood. In addition, it is also necessary to evaluate new allergens from novel protein sources that may pose a new risk for consumers. Technological development has allowed the expansion of advanced technologies for which their whole potential has not been entirely exploited and could provide novel contributions to still unexplored molecular traits underlying both the structure of food allergens and the mechanisms through which they sensitize or elicit adverse responses in human subjects, as well as improving analytical techniques for their detection. This review presents cutting-edge instrumental techniques recently applied when studying structural and functional aspects of proteins, mechanism of action and interaction between biomolecules. We also exemplify their role in the food allergy research and discuss their new possible applications in several areas of the food allergy field.

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“…Currently, there is no generally accepted method for ITH hazard or risk evaluation. Some studies have reported potential approaches, such as the use of a passive cutaneous anaphylaxis (PCA) test, the Buehler guinea pig skin sensitization test method, and proteomics and protein sequence analyses (Krutz et al, 2019; Matsunaga et al, 2015; Maurer‐Stroh et al, 2019). Furthermore, during an exposure assessment, the exposure amount should be calculated on the basis of the dose metric, correlating with the incidence of toxicity.…”

Section: Introductionmentioning

confidence: 99%

Total dose defines the incidence of percutaneous IgE/IgG1 mediated immediate‐type hypersensitivity caused by papain

Yokozeki

Tobisawa

Ogasawara

et al. 2020

J of Applied Toxicology

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Assessment of human health risk requires an understanding of antigen dose metrics associated with toxicity. Whereas assessment of the human health risk for delayed‐type hypersensitivity is understood, the metrics remain unclear for percutaneous immediate‐type hypersensitivity (ITH) mediated by IgE/IgG1. In this work, we aimed to investigate the dose metric for percutaneous ITH mediated by IgE/IgG1 responses. Papain, which causes ITH via percutaneous sensitization in humans, was used to sensitize guinea pigs and mice. The total dose per animal or dose per unit area was adjusted to understand the drivers of sensitization. Passive cutaneous anaphylaxis (PCA) and enzyme‐linked immunosorbent assay (ELISA) for papain‐specific IgG1 enabled quantification of the response in guinea pigs. In mice, the number of antigen‐bearing B cells in the draining lymph nodes (DLN) was calculated using flow cytometry papain‐specific IgG1 and IgE levels were quantified by ELISA. PCA positive test rates and the amounts of antigen‐specific antibody corresponded with total dose per animal, not dose per unit area. Furthermore, the number of B cells taking up antigen within DLN also correlated with total dose. These findings indicate that the total antigen dose is the important metric for percutaneous IgE/IgG1‐mediated ITH.

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Proteomic and Bioinformatic Analyses for the Identification of Proteins With Low Allergenic Potential for Hazard Assessment

Cited by 17 publications

References 38 publications

Allergen false-detection using official bioinformatic algorithms

Allergen false-detection using official bioinformatic algorithms

New applications of advanced instrumental techniques for the characterization of food allergenic proteins

Total dose defines the incidence of percutaneous IgE/IgG1 mediated immediate‐type hypersensitivity caused by papain

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