CALUX measurements: Statistical inferences for the dose-response curve

M. Elskens, D. S. Baston, C. Stumpf, J. Haedrich, I. Keupers, K. Croes, M. S. Denison, W. Baeyens, L. Goeyens

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 (ECR 20-50-80) 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.

Original languageEnglish (US)
Pages (from-to)1966-1973
Number of pages8
JournalTalanta
Volume85
Issue number4
DOIs
StatePublished - Sep 30 2011

Fingerprint

Luciferases
Gene expression
Gene Expression
Uncertainty
Cells
Confidence Intervals
Dioxins
Nonlinear Dynamics
Bioassay
Sigmoid Colon
Reporter Genes
Biological Assay
Calibration
Hepatocellular Carcinoma
Assays
Genes
Cell Line
Polychlorinated Dibenzodioxins
1,4-dioxin

Keywords

  • Bioassay CALUX
  • Box-Cox transformation
  • Dose-response curve
  • Statistical inference

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Elskens, M., Baston, D. S., Stumpf, C., Haedrich, J., Keupers, I., Croes, K., ... Goeyens, L. (2011). CALUX measurements: Statistical inferences for the dose-response curve. Talanta, 85(4), 1966-1973. https://doi.org/10.1016/j.talanta.2011.07.014

CALUX measurements : Statistical inferences for the dose-response curve. / Elskens, M.; Baston, D. S.; Stumpf, C.; Haedrich, J.; Keupers, I.; Croes, K.; Denison, M. S.; Baeyens, W.; Goeyens, L.

In: Talanta, Vol. 85, No. 4, 30.09.2011, p. 1966-1973.

Research output: Contribution to journalArticle

Elskens, M, Baston, DS, Stumpf, C, Haedrich, J, Keupers, I, Croes, K, Denison, MS, Baeyens, W & Goeyens, L 2011, 'CALUX measurements: Statistical inferences for the dose-response curve', Talanta, vol. 85, no. 4, pp. 1966-1973. https://doi.org/10.1016/j.talanta.2011.07.014
Elskens M, Baston DS, Stumpf C, Haedrich J, Keupers I, Croes K et al. CALUX measurements: Statistical inferences for the dose-response curve. Talanta. 2011 Sep 30;85(4):1966-1973. https://doi.org/10.1016/j.talanta.2011.07.014
Elskens, M. ; Baston, D. S. ; Stumpf, C. ; Haedrich, J. ; Keupers, I. ; Croes, K. ; Denison, M. S. ; Baeyens, W. ; Goeyens, L. / CALUX measurements : Statistical inferences for the dose-response curve. In: Talanta. 2011 ; Vol. 85, No. 4. pp. 1966-1973.
@article{f2a6053881a24bca98b771059bb494f8,
title = "CALUX measurements: Statistical inferences for the dose-response curve",
abstract = "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 (ECR 20-50-80) 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.",
keywords = "Bioassay CALUX, Box-Cox transformation, Dose-response curve, Statistical inference",
author = "M. Elskens and Baston, {D. S.} and C. Stumpf and J. Haedrich and I. Keupers and K. Croes and Denison, {M. S.} and W. Baeyens and L. Goeyens",
year = "2011",
month = "9",
day = "30",
doi = "10.1016/j.talanta.2011.07.014",
language = "English (US)",
volume = "85",
pages = "1966--1973",
journal = "Talanta",
issn = "0039-9140",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - CALUX measurements

T2 - Statistical inferences for the dose-response curve

AU - Elskens, M.

AU - Baston, D. S.

AU - Stumpf, C.

AU - Haedrich, J.

AU - Keupers, I.

AU - Croes, K.

AU - Denison, M. S.

AU - Baeyens, W.

AU - Goeyens, L.

PY - 2011/9/30

Y1 - 2011/9/30

N2 - 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 (ECR 20-50-80) 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.

AB - 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 (ECR 20-50-80) 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.

KW - Bioassay CALUX

KW - Box-Cox transformation

KW - Dose-response curve

KW - Statistical inference

UR - http://www.scopus.com/inward/record.url?scp=80052178656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052178656&partnerID=8YFLogxK

U2 - 10.1016/j.talanta.2011.07.014

DO - 10.1016/j.talanta.2011.07.014

M3 - Article

C2 - 21872045

AN - SCOPUS:80052178656

VL - 85

SP - 1966

EP - 1973

JO - Talanta

JF - Talanta

SN - 0039-9140

IS - 4

ER -