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  Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity: a bioinformatics perspective

Herwig, R., Gmuender, H., Corvi, R., Bloch, K. M., Brandenburg, A., Castell, J., et al. (2016). Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity: a bioinformatics perspective. Archives of Toxikology, 90(9), 2215-2229. doi:10.1007/s00204-015-1617-3.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-4784-3 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-F9F5-3
Genre: Journal Article

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© Springer-Verlag Berlin Heidelberg 2016
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 Creators:
Herwig, R.1, Author              
Gmuender, H., Author
Corvi, R., Author
Bloch, K. M., Author
Brandenburg, A., Author
Castell, J., Author
Ceelen, L., Author
Chesne, C., Author
Doktorova, T. Y., Author
Jennen, D., Author
Jennings, P., Author
Limonciel, A., Author
Lock, E. A., Author
McMorrow, T., Author
Phrakonkham, P., Author
Radford, R., Author
Slattery, C., Author
Stierum, R., Author
Vilardell, M., Author
Wittenberger, T., Author
Yildirimman, R., AuthorRyan, M., AuthorRogiers, V., AuthorKleinjans, J., Author more..
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385701              

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Free keywords: Bioinformatics Carcinogenicity In vitro assays Inter-laboratory assessment Pre-validation Toxicogenomics
 Abstract: The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems, reports on robustness and reproducibility, when testing them independently in different laboratories, are still uncommon. Furthermore, there is limited knowledge about variability induced by the data analysis protocols. We have conducted an inter-laboratory study for testing chemical carcinogenicity evaluating two human in vitro assays: hepatoma-derived cells and hTERT-immortalized renal proximal tubule epithelial cells, representing liver and kidney as major target organs. Cellular systems were initially challenged with thirty compounds, genome-wide gene expression was measured with microarrays, and hazard classifiers were built from this training set. Subsequently, each system was independently established in three different laboratories, and gene expression measurements were conducted using anonymized compounds. Data analysis was performed independently by two separate groups applying different protocols for the assessment of inter-laboratory reproducibility and for the prediction of carcinogenic hazard. As a result, both workflows came to very similar conclusions with respect to (1) identification of experimental outliers, (2) overall assessment of robustness and inter-laboratory reproducibility and (3) re-classification of the unknown compounds to the respective toxicity classes. In summary, the developed bioinformatics workflows deliver accurate measures for inter-laboratory comparison studies, and the study can be used as guidance for validation of future carcinogenicity assays in order to implement testing of human in vitro alternatives to animal testing.

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Language(s): eng - English
 Dates: 2015-11-022016-09
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: PMID: 26525393
DOI: 10.1007/s00204-015-1617-3
ISSN: 1432-0738 (Electronic)0340-5761 (Print)
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Title: Archives of Toxikology
Source Genre: Journal
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Publ. Info: Heidelberg : Springer
Pages: - Volume / Issue: 90 (9) Sequence Number: - Start / End Page: 2215 - 2229 Identifier: -