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From genome-wide arrays to tailor-made biomarker readout – Progress towards routine analysis of skin sensitizing chemicals with GARD

Forreryd, Andy LU ; Zeller, Kathrin S. LU ; Lindberg, Tim LU ; Johansson, Henrik LU and Lindstedt, Malin LU (2016) In Toxicology in Vitro 37. p.178-188
Abstract

Allergic contact dermatitis (ACD) initiated by chemical sensitizers is an important public health concern. To prevent ACD, it is important to identify chemical allergens to limit the use of such compounds in various products. EU legislations, as well as increased mechanistic knowledge of skin sensitization have promoted development of non-animal based approaches for hazard classification of chemicals. GARD is an in vitro testing strategy based on measurements of a genomic biomarker signature. However, current GARD protocols are optimized for identification of predictive biomarker signatures, and not suitable for standardized screening. This study describes improvements to GARD to progress from biomarker discovery into a reliable and... (More)

Allergic contact dermatitis (ACD) initiated by chemical sensitizers is an important public health concern. To prevent ACD, it is important to identify chemical allergens to limit the use of such compounds in various products. EU legislations, as well as increased mechanistic knowledge of skin sensitization have promoted development of non-animal based approaches for hazard classification of chemicals. GARD is an in vitro testing strategy based on measurements of a genomic biomarker signature. However, current GARD protocols are optimized for identification of predictive biomarker signatures, and not suitable for standardized screening. This study describes improvements to GARD to progress from biomarker discovery into a reliable and cost-effective assay for routine testing. Gene expression measurements were transferred to NanoString nCounter platform, normalization strategy was adjusted to fit serial arrival of testing substances, and a novel strategy to correct batch variations was presented. When challenging GARD with 29 compounds, sensitivity, specificity and accuracy could be estimated to 94%, 83% and 90%, respectively. In conclusion, we present a GARD workflow with improved sample capacity, retained predictive performance, and in a format adapted to standardized screening. We propose that GARD is ready to be considered as part of an integrated testing strategy for skin sensitization.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
GARD, In vitro assay, Predictive genomic biomarker signature, Skin sensitization
in
Toxicology in Vitro
volume
37
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:84992313061
  • wos:000387198300021
ISSN
0887-2333
DOI
10.1016/j.tiv.2016.09.013
language
English
LU publication?
yes
id
0a695dbe-6c3f-44ae-90dc-828a546b54a7
date added to LUP
2016-11-04 09:15:43
date last changed
2017-07-30 05:16:48
@article{0a695dbe-6c3f-44ae-90dc-828a546b54a7,
  abstract     = {<p>Allergic contact dermatitis (ACD) initiated by chemical sensitizers is an important public health concern. To prevent ACD, it is important to identify chemical allergens to limit the use of such compounds in various products. EU legislations, as well as increased mechanistic knowledge of skin sensitization have promoted development of non-animal based approaches for hazard classification of chemicals. GARD is an in vitro testing strategy based on measurements of a genomic biomarker signature. However, current GARD protocols are optimized for identification of predictive biomarker signatures, and not suitable for standardized screening. This study describes improvements to GARD to progress from biomarker discovery into a reliable and cost-effective assay for routine testing. Gene expression measurements were transferred to NanoString nCounter platform, normalization strategy was adjusted to fit serial arrival of testing substances, and a novel strategy to correct batch variations was presented. When challenging GARD with 29 compounds, sensitivity, specificity and accuracy could be estimated to 94%, 83% and 90%, respectively. In conclusion, we present a GARD workflow with improved sample capacity, retained predictive performance, and in a format adapted to standardized screening. We propose that GARD is ready to be considered as part of an integrated testing strategy for skin sensitization.</p>},
  author       = {Forreryd, Andy and Zeller, Kathrin S. and Lindberg, Tim and Johansson, Henrik and Lindstedt, Malin},
  issn         = {0887-2333},
  keyword      = {GARD,In vitro assay,Predictive genomic biomarker signature,Skin sensitization},
  language     = {eng},
  month        = {12},
  pages        = {178--188},
  publisher    = {Elsevier},
  series       = {Toxicology in Vitro},
  title        = {From genome-wide arrays to tailor-made biomarker readout – Progress towards routine analysis of skin sensitizing chemicals with GARD},
  url          = {http://dx.doi.org/10.1016/j.tiv.2016.09.013},
  volume       = {37},
  year         = {2016},
}