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

  • 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.

  • 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.

  • 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.

  • COMPARE Allergen Database

    Development and annual update of a database of protein allergen sequences is ongoing. The seventh version of the database was released in January 2023. Throughout the year, the team re-initiated and conducted the 10-month-long process leading to the next annual update of the COMPARE Database which contains 2,631 allergen sequences. 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

    Bayer CropScience

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Committee Publications

A Multi-Laboratory Evaluation of a Common In Vitro Pepsin Digestion Assay Protocol Used in Assessing the Safety of Novel Proteins

Evaluation of the potential allergenicity of proteins derived from genetically modified foods has involved a weight of evidence approach that incorporates an evaluation of protein digestibility in pepsin.

Read more

Agricultural Biotechnology Safety Assessment

Genetically modified (GM) crops were first introduced to farmers in 1995 with the intent to provide better crop yield and meet the increasing demand for food and feed.

Read more

Allergic Sensitization: Food- and Protein-Related Factors

Presented here are emerging capabilities to precisely measure endogenous allergens in soybean and maize, consideration of food matrices on allergens, and proteolytic activity of allergens.

Read more

Allergic Sensitization: Host-Immune Factors

Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context.

Read more

Allergic Sensitization: Screening Methods

Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and ...

Read more

Assessment of Potential Adjuvanticity of Cry Proteins

Genetically modified (GM) crops have achieved success in the marketplace and their benefits extend beyond the overall increase in harvest yields to include lowered use of insecticides and decreased carbon dioxide emissions. The most widely grown GM crops contain gene/s for targeted insect protection, herbicide tolerance, or ...

Read more

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