The GARD™ assay for potency assessment of skin sensitizing chemicals
Kathrin S. Zeller, Andy Forreryd, Tim Lindberg, Ann-Sofie Albrekt, Aakash Chawade, Malin Lindstedt
Dept. of Immunotechnology, Lund University, Lund, Sweden; Swedish University of Agricultural Sciences, Alnarp, Sweden
Summary
The GARD assay is a cell-based transcriptional biomarker assay for the prediction of chemical ensitizers1 targeting key event 3, dendritic cell activation, of the skin sensitization AOP. Here, we present a modified assay based on Random Forest modelling, which is capable of predicting CLP
potency classes (1A – strong sensitizers, 1B – weak sensitizers, no category – non-sensitizers) as described by the European CLP regulation with an accuracy of 75 % (no cat), 75 % (1B) and 88 % (1A) based on a test set consisting of 18 chemicals previously unseen to the model.
We further can link the activation of distinct pathways to the chemical protein reactivity, showing that our transcriptomic approach can reveal information contributing to the understanding of underlying mechanisms in sensitization.
Results and Discussion
We here present a potency prediction approach based on a Random Forest model and 18 transcripts. 18 chemicals previously unseen to the model were classified as shown in Tables 1, 4 and Fig. 1. Interestingly, diethyl maleate, misclassified as 1A instead of 1B, is a human potency class 2 according to4, and iodopropynyl butylcarbamate, wrongly predicted as 1B instead of 1A, is classified as human potency class 44. Thus, the model seems to show more agreement with human data than CLP classifications (mainly derived from animal data) based on this limited dataset. Also Fig. 1C supports the hypothesis, that both data and model contain information allowing the prediction of human potency.
Furthermore, Key Pathway Advisor analysis reveals that these data can be used to investigate the cellular response in more detail (Table 3). In conclusion, we show that the modified GARD assay is capable of providing potency information, which is imperative for quantitative risk assessment of chemical sensitizers.
The GARD assay for potency assessment of skin sensitizing chemicals_ESTIV 2016_Zeller_p
GARD™ – The story
Olivia Larne, Andy Forreryd, Ann Sofie Albrekt, Carl Arne Krister Borrebaeck, Henrik Johansson, Malin Lindstedt
SenzaGen, Sweden, Lund, Department of Immunotechnology, Lund University, Sweden, Lund
Background
To prevent the general population for unnecessary exposure to sensitizing substances, the substances have to be safety tested. Regulatory authorities and economic interests request animal free methodology. Genomic Allergen Rapid Detection, GARD, is an in vitro test developed for the prediction of sensitizing chemicals. It is based on differential expression of disease-associated genomic biomarkers in a human myeloid dendritic cell line.
Here, we describe the development of the GARD platform and its downstream innovations.
Poster:
GARD – The Story_ESTIV 2016
GARD™ – the future of sensitization testing and safety assessment of chemicals using a genomic-based platform
BACKGROUND
Genomic Allergen Rapid Detection, GARD, is an in vitro test developed for the prediction of sensitizing chemicals. It is based on differential expression of disease-associated genomic biomarkers in a human myeloid dendritic cell line.
Here, we describe the development, scientific validation, applications and the current state of the GARD platform. The scientific rationale behind the use of genomic biomarker signatures are detailed, linked to the AOP in a biological context, and to advantages realized through multivariate computational prediction models in a technological context.
RESUME
The GARD assay is elastic, it can be used for several applications. Today, two are developed:
GARDskin
– Hazard identification of skin sensitizers
– Accuracy: ~90%
– Initiated ECVAM validation (OECD TGP no. 4.106)
GARDair
– Hazard identification of respiratory sensitizers
– Accuracy: ~85%
GARD™ – the future of sensitization testing and safety assessment of chemicals, using a genomics-based platform
Henrik Johansson, Andy Forreryd, Olivia Larne, Ann Sofie Albrekt, Carl Arne Krister Borrebaeck, Malin Lindstedt
SenzaGen, Sweden, Lund, Department of Immunotechnology, Lund University, Sweden, Lund
Background
Genomic Allergen Rapid Detection, GARD, is an in vitro test developed for the prediction of sensitizing chemicals. It is based on differential expression of disease-associated genomic biomarkers in a human myeloid dendritic cell line.
Here, we describe the development, scientific validation, applications and the current state of the GARD platform. The scientific rationale behind the use of genomic biomarker signatures are detailed, linked to the AOP in a biological context, and to advantages realized through multivariate computational prediction models in a technological context.
Resume
GARDskin
– Hazard identification of skin sensitizers
– Accuracy: ~90%
– Initiated ECVAM validation (OECD TGP no. 4.106)
GARDair
– Hazard identification of respiratory sensitizers
– Accuracy: ~85%
Anki Malmborg Hager elected one of the two most powerful people among Lund technology companies according to Rapidus ranking
The news site Rapidus has been looking into nealy 180 companies of extended IDEON business park in Lund, Sweden in a unique survey of decision-makers of the region. Ericsson veteran Tord Wingren and Alligator Bioscience co-founder Anki Malmborg-Hager were ranked two of the most powerful people among Lund technology companies.
Rapidus writes:
Leeding up to the expansion of the concept of Ideon, Rapidus went through the records of company boards and chief executives of all technology companies which have their registered office at Ideon Medicon Village, Mobile Heights Center and Edison Park.
In total it ads up to around 700 decision makers of almost 180 companies. Most of them only sit on one board or CEO positions however 56 of these people have posiotions in more than one technology company on the extended Ideon area. At the top of the list are a dozen people with at least three appointments, including the CEO of Jolife Erik von Schenck and Professor Carl Borrebaeck, who among several appointments is on the board of Alligator Bioscience and Clinical Laserthermia Systems.
Read the full news at Rapidus site (only subscribers)
SenzaGen starts blogging for Swedish leading financial newspaper Dagens Industri.
Follow our CEO, Anki Malmborg Hager here on the new blog at our web site under Mixed Media/blogs or at Di Gasell.
The blog will be in Swedish
SenzaGen nominated for Guldråttan -the Golden Rat
SenzaGen has been nominated for the honorable price “Guldråttan” -the Golden Rat, a prize awarded by Djurens Rätt (the Animal Rights) to companies that make exceptional contribution to animal wellfare.
SenzaGen is able to greatly reduce animal use with their animal free allergy tests for cosmetic ingredients, raw material production and the pharmaceutical industries. With the company’s test GARD, which is performed in vitro, the number of animals used for testing in these industries can be heavily reduced and now that SenzaGen is expanding globally, the impact can be even greater.
“Guldråttan is Sweden’s finest animal rights prize and awarded since 1987 by Djurens Rätt to a person or persons who have made an exceptional contribution during the year to animal well fare” Djurens Rätt says ontheir site.
It is now possible to vote on who should be awarded Guldråttan 2016. Voting will run until April 10 and the winner will be presented at Djurens Rätts National Conference in Stockholm on 14-15 May.
Participate and vote at http://www.djurensratt.se/guldrattan2016 (in Swedish) Link no longer available
SenzaGen is presenting at a hosted session at Society of Toxicology 55th Annual Meeting in New Orleans March 15, 2016
SenzaGen Senior Scientist, Dr. Henrik Johansson will give a presentation at an exhibitor hosted session at the Society of Toxicology 55th Annual Meeting in New Orleans, 15th of March.
The meeting promises more than 150 scientific sessions, approximately 350 ToxExpo exhibitors offering you the latest information on services and technology, thousands of abstract presentations, continuing education courses, awards presentations, receptions, career guidance and support, and more.
The topic for Dr. Johansson’s presentation, Genomics—The Future of Sensitization Testing and Safety Assessment is: In vitro testing in human cellines using genomic technology is the future in safety testing of chemicals and proteins. SenzaGen is presenting their use of genomics for sensitization testing with GARD assays for skin and respiratory sensitization. Using +200 biomarkers enables better predictions, including potency information.
This session is an Exhibitor-Hosted Session. Although not an official part of the SOT Annual Meeting scientific program, its presentation is permitted by the Society.
The presentation will cover
- Accurate and convenient safety assessment of chemical sensitizers using GARD, an in vitro assay based on genomic biomarker signatures
- How genomic readouts can help facilitate simple models that effectively monitors a complex reality
- Versatile test systems allowing for a broad applicability domain
Attendees are welcomed from researcher community, industry, manufacturers, regulatory agencies, consultants, CROs and every one interested in safety testing of chemical compounds.
Details: Genomics—The Future of Sensitization Testing and Safety Assessment
Exhibition hall, Room 211 Tuesday, March 15, 1:30 PM to 2:30 PM
