Details
| Original language | English |
|---|---|
| Pages (from-to) | 36-41 |
| Number of pages | 6 |
| Journal | Mutation Research - Genetic Toxicology and Environmental Mutagenesis |
| Volume | 744 |
| Issue number | 1 |
| Early online date | 9 Dec 2011 |
| Publication status | Published - 11 Apr 2012 |
Abstract
Validation activities of the BALB/c 3T3 cell transformation assay (CTA) - a test method used for the assessment of the carcinogenic potential of compounds - have revealed the need for statistical analysis tailored to specific features of BALB/c 3T3 CTA data. Whereas a standard statistical approach for the Syrian hamster embryo (SHE) CTA was considered sufficient, an international expert group was gathered by the European Centre for the Validation of Alternative Methods (ECVAM) to review commonly applied statistical approaches for BALB/c 3T3 CTA. As it was concluded that none of the commonly applied approaches is entirely appropriate, two novel statistical approaches were found to be recommended for the evaluation of BALB/c 3T3 CTA data accounting for possible non-monotone concentration-response relationship and variance heterogeneity: a negative binomial generalised linear model with William's-type downturn-protected trend tests and a normalisation of the data by a specific transformation allowing for application of a general linear model that estimates effects assuming a normal distribution with William's-type protected tests. Both approaches are described in this article and their performance and the quality of the results they generate is demonstrated using exemplary data. Our work confirmed that both approaches are suitable for the statistical analysis of BALB/c 3T3 CTA data and that each of them is superior to commonly used methods. Furthermore, a procedure dichotomising data into negatives and positives is proposed which allows re-testing in cases where inconclusive data are encountered. The scripts of the statistical evaluation programs written in R - a freely available statistical software - are appended including exemplary outputs (Appendix A).
Keywords
- (Negative binomial) Generalised linear model, Analysis programme, BALB/c 3T3 cell transformation assay, Non-monotone concentration response, Statistical analysis, William's-type protected tests
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Genetics
- Environmental Science(all)
- Health, Toxicology and Mutagenesis
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In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 744, No. 1, 11.04.2012, p. 36-41.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Two new approaches to improve the analysis of BALB/c 3T3 cell transformation assay data
AU - Hoffmann, Sebastian
AU - Hothorn, Ludwig A.
AU - Edler, Lutz
AU - Kleensang, André
AU - Suzuki, Masaya
AU - Phrakonkham, Pascal
AU - Gerhard, Daniel
PY - 2012/4/11
Y1 - 2012/4/11
N2 - Validation activities of the BALB/c 3T3 cell transformation assay (CTA) - a test method used for the assessment of the carcinogenic potential of compounds - have revealed the need for statistical analysis tailored to specific features of BALB/c 3T3 CTA data. Whereas a standard statistical approach for the Syrian hamster embryo (SHE) CTA was considered sufficient, an international expert group was gathered by the European Centre for the Validation of Alternative Methods (ECVAM) to review commonly applied statistical approaches for BALB/c 3T3 CTA. As it was concluded that none of the commonly applied approaches is entirely appropriate, two novel statistical approaches were found to be recommended for the evaluation of BALB/c 3T3 CTA data accounting for possible non-monotone concentration-response relationship and variance heterogeneity: a negative binomial generalised linear model with William's-type downturn-protected trend tests and a normalisation of the data by a specific transformation allowing for application of a general linear model that estimates effects assuming a normal distribution with William's-type protected tests. Both approaches are described in this article and their performance and the quality of the results they generate is demonstrated using exemplary data. Our work confirmed that both approaches are suitable for the statistical analysis of BALB/c 3T3 CTA data and that each of them is superior to commonly used methods. Furthermore, a procedure dichotomising data into negatives and positives is proposed which allows re-testing in cases where inconclusive data are encountered. The scripts of the statistical evaluation programs written in R - a freely available statistical software - are appended including exemplary outputs (Appendix A).
AB - Validation activities of the BALB/c 3T3 cell transformation assay (CTA) - a test method used for the assessment of the carcinogenic potential of compounds - have revealed the need for statistical analysis tailored to specific features of BALB/c 3T3 CTA data. Whereas a standard statistical approach for the Syrian hamster embryo (SHE) CTA was considered sufficient, an international expert group was gathered by the European Centre for the Validation of Alternative Methods (ECVAM) to review commonly applied statistical approaches for BALB/c 3T3 CTA. As it was concluded that none of the commonly applied approaches is entirely appropriate, two novel statistical approaches were found to be recommended for the evaluation of BALB/c 3T3 CTA data accounting for possible non-monotone concentration-response relationship and variance heterogeneity: a negative binomial generalised linear model with William's-type downturn-protected trend tests and a normalisation of the data by a specific transformation allowing for application of a general linear model that estimates effects assuming a normal distribution with William's-type protected tests. Both approaches are described in this article and their performance and the quality of the results they generate is demonstrated using exemplary data. Our work confirmed that both approaches are suitable for the statistical analysis of BALB/c 3T3 CTA data and that each of them is superior to commonly used methods. Furthermore, a procedure dichotomising data into negatives and positives is proposed which allows re-testing in cases where inconclusive data are encountered. The scripts of the statistical evaluation programs written in R - a freely available statistical software - are appended including exemplary outputs (Appendix A).
KW - (Negative binomial) Generalised linear model
KW - Analysis programme
KW - BALB/c 3T3 cell transformation assay
KW - Non-monotone concentration response
KW - Statistical analysis
KW - William's-type protected tests
UR - http://www.scopus.com/inward/record.url?scp=84859426993&partnerID=8YFLogxK
U2 - 10.1016/j.mrgentox.2011.12.002
DO - 10.1016/j.mrgentox.2011.12.002
M3 - Article
C2 - 22178130
AN - SCOPUS:84859426993
VL - 744
SP - 36
EP - 41
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
SN - 1383-5718
IS - 1
ER -