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 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

    Bayer CropScience

Committee Events

HESI COMPARE Database Annual Meeting

HESI COMPARE Database, Virtual

The HESI COMPrehensive Allergen REsource (COMPARE) Steering Team will meet to plan for the upcoming COMPARE 2024 review cycle.

Read more

PATB Committee Protein Toxins Workshop

Virtual workshop, hosted by the HESI PATB Committee

The HESI Protein Allergens, Toxins, and Bioinformatics (PATB) Committee is hosting a virtual workshop focusing on the state of the science for a wide array of protein toxins classes, MOAs, structures, activity, and general biology. Additionally, the workshop will cover the bioinformatics analysis of protein toxins and how ...

Read more

PATC Non-IgE Mediated Immune Reactions to Foods Workshop

Rome, Italy

This workshop provided an opportunity to discuss the current state of the science in immunologic mechanisms of non-IgE mediated food allergy with a specific emphasis on use of these data to assess food safety.

Read more

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The HESI Protein Allergens, Toxins, and Bioinformatics (PATB) Committee is hosting a virtual workshop focusing on the state of the science for a wide array of protein toxins classes, MOAs, structures, activity, and general biology. Additionally, the workshop will cover the bioinformatics analysis of protein toxins and how to leverage computational biology for protein toxins identification/characterization, with in silico approaches.

The Protein Toxins Workshop will serve the dual purpose of learning from the experts in the field about the state of the science as well as assessing the translation of knowledge to practical applications, e.g., into weight-of-evidence approaches for the safety assessment of biotechnology products. The workshop aims to gain insight into how feasible/useful (or not) a protein toxin database could be in risk assessment/product development. This meeting will serve as an informational platform about HESI and will demonstrate the advances in protein toxins research, presented by international experts, and will help inform the development of novel approaches for the identification and classification of potential toxicity risk in novel proteins.

Details

  • Date: Wednesday, 21 October 2020 - Thursday, 22 October 2020
  • Time: 9:00 AM - 12:00 PM EST
  • Registration: Details coming soon
PATC_resize

Workshop Program Outline (subject to change)

Wednesday, 21 October 2020

  • 9:00 AM - Opening Remarks (Dr. Laura Privalle, BASF Corporation)
    • From protein toxins to biotechnology products
    • Setting the stage; considerations for publication of meeting report
  • 9:30 AM - Brief Codex Discussion
    • Allergenicity assessment vs. toxins/toxicity assessment
  • 10:00 AM - Terrestrial Toxins
  • 11:30 AM - Marine Toxins

 

Thursday, 22 October 2020

  • 9:00 AM - Bacterial Toxins
  • 10:30 AM - Bioinformatics & Computational Biology in Protein Toxins Research

 

For more information, please contact the PATB Committee's Senior Scientific Program Manager, Dr. Lucilia Mouriès at lmouries@hesiglobal.org.

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The Health and Environmental Sciences Institute (HESI) Protein Allergens, Toxins, and Bioinformatics (PATB) committee will be hosting a webinar to discuss emerging opportunities and innovations in the biotechnology and food safety assessment arenas. See details below!

Details

  • Date: Wednesday, May 22, 2019
  • Time: 11 AM - 12:30 PM EST
  • Registration: Click here to register.
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Speakers:

  • Scott McClain, Regulatory Product Safety Scientist, Syngenta Crop Protection (USA), PATB Committee Co-Chair
  • Lars Poulsen, Head of Research, Allergy Clinic, Copenhagen University Hospital at Gentofte (Denmark), Member of the COMPARE Database Peer-Review Expert Panel

Advances in agricultural and food biotechnology bring the opportunity to improve the way we grow food and feed crops. As part of the requirements to ensure food safety, it is vital to mitigate potential risks of introducing new allergens or unintended components in the food chain that could induce adverse reactions in humans.

The Health and Environmental Sciences Institute (HESI) Protein Allergens, Toxins, and Bioinformatics (PATB) committee engages international collaborative teams of academics, clinicians, regulators, and industry scientists who conduct research, design and populate public database resources, and convene trainings on the use and evaluation of biotechnology products.  The PATB oversees the creation, maintenance, and distribution of the Comprehensive Protein Allergen Resource (COMPARE) Database whose use in conjunction bioinformatic tools, offers an effective means for assessing allergenic potential of novel food proteins. 

Webinar attendees will:

  • Learn directly from experts in the committee about the nuts and bolts of food safety assessment of biotechnology products, the committee contributions to the field and new emerging issues
  • Engage in an interactive discussion about emerging opportunities, challenges, and innovations in the biotechnology and food safety assessment arenas
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Location: Tivoli Hotel and Congress Center - Copenhagen, Denmark
Dates: October 17 - 18, 2018

There will also be another meeting at the Tivoli Hotel and Congress Center in Copenhagen, Denmark, called FAAM 2018, a EAACI Focused Meeting. FAAM 2018 will take place from 18 -20 October 2018. Please consider attending both events! Find more information on the event here.

 

About
In the growing field of allergy research, scientists can approach protein characterization and allergy hazard assessment in diverse ways. The Health and Environmental Sciences Institute (HESI) Protein Allergens, Toxins, and Bioinformatics (PATB) committee supports original basic research that seeks to uncover the interplay between protein allergenicity and the physicochemical properties of allergenic proteins. The PATB also oversees the creation, maintenance and distribution of the Comprehensive Protein Allergen Resource (COMPARE) Database whose use in conjunction bioinformatic tools, offers an effective means for assessing allergenic potential of novel food proteins.  PATB’s focus on basic allergy research, coupled with bioinformatic methods for allergenic hazard assessment is unique within the scientific community as it supports an ever-increasing awareness of allergenicity among consumers and regulators. Topics to be covered in this workshop will include historic aspects of food allergy assessment, the evolution of bioinformatics as it relates to allergy assessment, and recent changes in regulations regarding novel food proteins.

This educational workshop will cover advances in protein allergy research and inform the use of novel approaches for the identification of potential food allergens. This event will be of interest to government regulators, those involved in food allergy and celiac disease research, and scientists involved in food safety and risk assessment.

dreamstime_xl_71979237

 

Objectives

Evaluate bioinformatics approaches to characterize the allergenicity potential of novel proteins and inform allergy safety assessment.

Discuss real-world examples of: 1) a product development case-study describing the utility of bioinformatics in protein characterization, and 2) a practical application of the EFSA 2017 Guidance.

Provide insights from new research, ranging from modifications of allergen epitopes at the single amino-acid level, to using protein structural modeling for allergenicity prediction, to the relation between enzymes and allergenic activity.

Introduction

Overview of contributions and research of the HESI PATB to Bioinformatics Analysis of the Potential Allergenicity of Novel Proteins
Greg Ladics, Dupont (Download Presentation)

 

Session I: Bioinformatics Approaches to Protein Characterization and Allergy Safety Assessment
A history of bioinformatics: development of in silico approaches to evaluate food proteins 
Andre Silvanovich, Bayer Crop Science (Download Presentation) Protein sequence analysis tools and resources to detect potential allergens
Rob Finn, European Bioinformatics Institute (EBI) (Download Presentation) Case Study: Allergenic risk of insect proteins
Kitty Verhoeckx, TNO (Download Presentation) The COMPARE Allergen Database: a public, comprehensive protein allergen resource for allergenicity safety assessment
Lars Poulsen, University of Copenhagen (Download Presentation) Novel methods to identify allergenicity potential of proteins
Sebastian Maurer-Stroh, A*STAR Bioinformatics Institute (BII), Singapore (Download Presentation)

 

Session II: Other Considerations for Allergen Safety Assessment

The PATB “Allergen Rebuild Project”: can the conservative replacement of amino acids in an allergen epitope affect IgE binding and cross-reactivity?
Ronald van Ree, Academic Medical Center, University of Amsterdam Development of a Random Forest model for predicting allergenicity of new and modified proteins
Tanja Krone, TNO Cross-reactive carbohydrate determinants and allergenicity 
Edzard Spillner, Aarhus University (Download Presentation)

 

Session III: Non-IgE Mediated Allergy

Overview of known non-IgE mediated diseases and progress in immunology of non-IgE diseases
Antonella Cianferoni, Children’s Hospital of Philadelphia (Download Presentation) In silico tools to predict potential celiac disease toxicity 
Frits Koning, Leiden University (Download Presentation) Application of EFSA 2017 bioinformatic guidance for non-IgE mediated immune disease
Andre Silvanovich, Bayer Crop Science (Download Presentation) Considerations for small peptide analyses in SGF
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Committee Publications

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

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

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

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

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

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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