Protein Allergens, Toxins, and Bioinformatics (PATB) Committee

Mission Statement

The PATB is committed to advancing the scientific understanding of the relevant parameters defining allergenic proteins and protein toxins, and encouraging the development of reliable and accurate methodologies for characterizing the allergenic potential of novel proteins in order to leverage the potential of bioinformatics approaches in accomplishing these efforts.

Renaming the Committee: PATC to PATB

Formerly the Protein Allergenicity Technical Committee (PATC), the committee has adopted a new designation, the Protein Allergens, Toxins and Bioinformatics (PATB) Committee, to embrace a broader scope, expertise, interests, and collaborators in the fields of bioinformatics and protein toxins, while strengthening its core focus in allergenicity.

Call for Participants!

New Project on Organoids as NAMs for Celiac Disease Modeling

The Protein Allergens, Toxins and Bioinformatics (PATB) Committee is seeking partners to help launch a new project to advance methods for the assessment of gluten-like peptide sequences that could trigger Celiac disease (CD). The proposed pilot study will test the potential of microbial derived peptides to mimic gluten peptides using organoid models.

The project will have relevance for those involved in the evaluation of genetically modified crops, novel foods, or proteins (e.g., for food ingredients) produced via precision fermentation or microbial production systems as well as those with an interest in NAMs for food safety and clinicians/researchers involved in the study of Celiac Disease pathology and immunology.

By involving in vitro NAMs and patient derived materials to generate CD-organoids, this study is anticipated to generate both biological and methodological advancements. We are seeking additional financial support and expertise to ensure that the design and impact of the study is optimized. Your involvement will be enhanced by significant contributions in-kind by a clinical collaborator from Harvard University with expertise in developing these in vitro organoid systems! Peptides will be generated this fall and bench work to launch in early 2024.

As with all HESI projects, the success and impact of this initiative will depend on engaging thought leaders and international stakeholders, from government regulators to clinicians, to crop protection, food biotechnology, and biomedical industry experts, academics, and representatives from other relevant organizations.

Interested in finding out more?

Please contact Dr. Lucilia Mouriès at lmouries@hesiglobal.org

Project Background

Current risk assessment approaches for novel foods include amino acid sequence comparison searches, with comparisons being made to approximately 70 known 9-amino acid celiac epitopes.

However, sequence comparisons have shortcomings. Matching of novel proteins to known celiac epitopes can lead to high false positive rates; for example, many common proteins such as zeins, kafirins, and legumins as well as proteins found in pigs and cows have at least one celiac peptide match.

Furthermore, it has been proposed that changes in the Human gut microbiota can promote CD development in genetically susceptible individuals. A number of microbially derived peptides that share sequence similarities to HLA-DQ2.5-restricted gliadin determinants known to be associated with CD have been identified and shown to activate disease-relevant, gliadin-reactive T-cells isolated from CD patients. Yet, activation of T-cells in the gut is a downstream step in the cascade of events for CD. It is unknown if such peptides, when ingested as foods would pass the intestinal barrier, and reach the T-cells in the gut.

In order to reflect the clinical scenario more wholistically, we propose the use of patient-derived human gut organoids as a model system to determine the celiac potential of a protein containing a single putative CD epitope. Organoids are ideal for this use because they replicate many features of clinical disease in a disease-relevant human in vitro model system.

Working Groups

  • Celiac Disease

    Project initiated in October 2023. A call for participants was released by the committee during Summer 2023 and a team 10 participants from 9 organizations has been assembled. This pilot study will test the potential of microbial derived peptides to mimic gluten peptides in activating early events in the cascade triggering Celiac Disease, using organoid models derived from Celiac patients and healthy individuals. The committee is aiming to evaluate the clinical relevance of non-gluten peptides that share similarity with the disease-causing gluten peptides, in triggering Celiac disease. Experimental work will be conducted thanks to a collaboration with leading Celiac Disease experts at Massachusetts General Hospital.

  • Digestibility Working Group: Food Matrix Project

    This research project aims to study the impact of food matrices on the digestibility of proteins and complements the work completed on digestibility in vitro models, by testing whether protocols that take matrices into account would provide a better discrimination of allergens and nonallergens than protocols focusing on purified proteins in solution. In 2020, the experimental work was concluded. The data are being analyzed and a publication is planned in 2021.

  • Immunogenicity

    This working group aims to examine application of an in vitro protocol for identifying specific T-cells and antibodies from nonallergic and allergic patients to pairs of proteins from the same protein family but with different allergenicity. After some delays in the anticipated start date due to the COVID-19 pandemic, the project officially received the green light from the leading institution, Copenhagen University Hospital at Gentofte (Copenhagen, Denmark) in late 2020.

  • Protein Toxins Task Force

    The goals of the task force are to (1) investigate approaches for identifying protein toxins and (2) suggest specific guidelines to identify new protein toxins. In 2019, the task force undertook a literature review to identify current approaches being used and leading experts in the topic to design the workshop held in 2020. The workshop covered recent advances in protein toxins biology, described the use of computational biology for protein toxins identification and characterization with in silico approaches, and discussed the applicability of existing tools and resources for safety assessment of novel food biotechnology products.

  • COMPARE Allergen Database

    Development and annual update of a database of protein allergen sequences is ongoing. The eighth version of the database was released in January 2024. Throughout the year, the team re-initiates and conducts the 10-month-long process leading to the next annual update of the COMPARE Database. Visit COMPARE at https://comparedatabase.org for more details.

HESI Staff

Leadership Team

  • Ronald van Ree, PhD

    Academic Medical Center, University of Amsterdam

  • Andre Silvanovich, PhD

    Retired from Bayer CropScience

Committee Events

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Committee Publications

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“From Protein Toxins to Applied Toxicological Testing” virtual workshop identifies the need for a bioinformatic framework to assess novel food protein safety

Regulatory Toxicology and Pharmacology, 2022

Bauman PA, Doxey AC, Eberini I, Islamovic E, Jungo F, Kessenich C, ...

The HESI Protein Allergens, Toxins, and Bioinformatics Committee, and the Society of Toxicology Food Safety Specialty Section co-hosted a virtual workshop titled “From Protein Toxins to Applied Toxicological Testing”.  Key outcomes of the workshop are highlighted here.

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The COMPARE Database: A Public Resource for Allergen Identification, Adapted for Continuous Improvement

Frontiers in Allergy, 2021

van Ree R, Ballerda DS, Berin MC, Beuf L, Chang A, Gadermaier G, ...

The availability of databases identifying allergenic proteins via a transparent and consensus-based scientific approach is of prime importance to support the safety review of genetically-modified foods and feeds, and public safety in general. Over recent years, screening for potential new allergens sequences has become ...

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Protease Resistance of Food Proteins: A Mixed Picture For Predicting Allergenicity but a Useful Tool for Assessing Exposure

Clinical and Translational Allergy, 2018

Akkerdaas J, Totis M, Barnett B, Bell E, Davis T, Edrington T, ...

Susceptibility to pepsin digestion of candidate transgene products is regarded an important parameter in the weight-of-evidence approach for allergenicity risk assessment of genetically modified crops. It has been argued that protocols used for this assessment should better reflect physiological ...

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Variation in Seed Allergen Content From Three Varieties of Soybean Cultivated in Nine Different Locations in Iowa, Illinois, and Indiana

Frontiers in Plant Science, 2018

McClain S, Stevenson SE, Brownie C, Herouet-Guicheney C, ...

Soybean (Glycine max) is an important food stock, and also considered an allergenic food with at least eight well characterized allergens. However, it is a less prevalent allergen source than many other foods and is rarely life-threatening. Soybean is incorporated into commonly consumed foods, and therefore, the allergens pose ...

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Functional Classification of Protein Toxins as a Basis for Bioinformatic Screening

Scientific Reports, 2017

Negi SS, Schein CH, Ladics GS, Mirsky H, Chang P, Rascle JB, ...

Proteins are fundamental to life and exhibit a wide diversity of activities, some of which are toxic. Therefore, assessing whether a specific protein is safe for consumption in foods and feeds is critical. Simple BLAST searches may reveal homology to a known toxin, when in fact the protein may pose no real danger.

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