CALUX measurements: Statistical inferences for the dose–response curve

Chemical Activated LUciferase gene eXpression [CALUX] is a reporter gene mammalian cell bioassay used for detection and semi-quantitative analyses of dioxin-like compounds. CALUX dose–response curves for 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD] are typically smooth and sigmoidal when the dose is p...

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Bibliographic Details
Published in:	Talanta (Oxford) Vol. 85; no. 4; pp. 1966 - 1973
Main Authors:	Elskens, M., Baston, D.S., Stumpf, C., Haedrich, J., Keupers, I., Croes, K., Denison, M.S., Baeyens, W., Goeyens, L.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 30-09-2011 Elsevier
Subjects:	Analytical chemistry Animals Applied sciences Assessments Bioassay CALUX Biological Assay - methods Biological Assay - standards Box–Cox transformation Calibration Cell Line, Tumor Chemistry Confidence Confidence intervals Dose-Response Relationship, Drug Dose–response curve Environmental Pollutants - analysis Environmental Pollutants - pharmacology Exact sciences and technology Gene Expression - drug effects Global environmental pollution Intervals Luciferases - genetics Mathematical models Mice Pollution Polychlorinated Dibenzodioxins - pharmacology Reference Standards Regression Analysis Statistical inference Uncertainty Bioassay CALUX Statistical inference Box–Cox transformation Dose–response curve Performance evaluation Uncertainty Chemical analysis Liver Activation Standard Reporter gene Quantitative analysis Dose-response curve Biochemical analysis Bioassay Non linear regression Enzyme Sample Estimation Luciferase Use Rodentia Prediction Biological indicator Concentration Calibration Method Malignant tumor Gene expression Confidence interval Vertebrata Mammalia Cell line Mouse Non linear model Oxidoreductases Box-Cox transformation Detection Comparative study Cancer
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Summary:	Chemical Activated LUciferase gene eXpression [CALUX] is a reporter gene mammalian cell bioassay used for detection and semi-quantitative analyses of dioxin-like compounds. CALUX dose–response curves for 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD] are typically smooth and sigmoidal when the dose is portrayed on a logarithmic scale. Non-linear regression models are used to calibrate the CALUX response versus TCDD standards and to convert the sample response into Bioanalytical EQuivalents (BEQs). Several complications may arise in terms of statistical inference, specifically and most important is the uncertainty assessment of the predicted BEQ. This paper presents the use of linear calibration functions based on Box–Cox transformations to overcome the issue of uncertainty assessment. Main issues being addressed are (i) confidence and prediction intervals for the CALUX response, (ii) confidence and prediction intervals for the predicted BEQ-value, and (iii) detection/estimation capabilities for the sigmoid and linearized models. Statistical comparisons between different calculation methods involving inverse prediction, effective concentration ratios (ECR20–50–80) and slope ratio were achieved with example datasets in order to provide guidance for optimizing BEQ determinations and expand assay performance with the recombinant mouse hepatoma CALUX cell line H1L6.1c3.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0039-9140 1873-3573
DOI:	10.1016/j.talanta.2011.07.014