Two new approaches to improve the analysis of BALB/c 3T3 cell transformation assay data

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dc.contributor.authorHoffmann, S.
dc.contributor.authorHothorn, L.A.
dc.contributor.authorEdler, L.
dc.contributor.authorKleensang, A.
dc.contributor.authorSuzuki, M.
dc.contributor.authorPhrakonkham, P.
dc.contributor.authorGerhard, D.
dc.date.accessioned2015-05-18T02:30:17Z
dc.date.available2015-05-18T02:30:17Z
dc.date.issued2012en
dc.description.abstractValidation 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.en
dc.identifier.citationHoffmann, S., Hothorn, L.A., Edler, L., Kleensang, A., Suzuki, M., Phrakonkham, P., Gerhard, D. (2012) Two new approaches to improve the analysis of BALB/c 3T3 cell transformation assay data. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 744(1), pp. 36-41.en
dc.identifier.doihttps://doi.org/10.1016/j.mrgentox.2011.12.002
dc.identifier.urihttp://hdl.handle.net/10092/10426
dc.language.isoen
dc.publisherUniversity of Canterbury. Mathematics and Statisticsen
dc.rights.urihttps://hdl.handle.net/10092/17651en
dc.subjectBALB/c 3T3 cell transformation assayen
dc.subjectstatistical analysisen
dc.subjectanalysis programmeen
dc.subjectnon-monotone concentration responseen
dc.subject(negative binomial) generalised linear modelen
dc.subjectWilliam's-type protected testsen
dc.subject.anzsrcFields of Research::31 - Biological sciences::3101 - Biochemistry and cell biology::310103 - Cell metabolismen
dc.subject.anzsrcField of Research::01 - Mathematical Sciences::0104 - Statistics::010401 - Applied Statisticsen
dc.titleTwo new approaches to improve the analysis of BALB/c 3T3 cell transformation assay dataen
dc.typeJournal Article
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