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Unkel, S.* ; Belka, C. ; Lauber, K.

On the analysis of clonogenic survival data: Statistical alternatives to the linear-quadratic model.

Radiat. Oncol. 11:11 (2016)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
Background: The most frequently used method to quantitatively describe the response to ionizing irradiation in terms of clonogenic survival is the linear-quadratic (LQ) model. In the LQ model, the logarithm of the surviving fraction is regressed linearly on the radiation dose by means of a second-degree polynomial. The ratio of the estimated parameters for the linear and quadratic term, respectively, represents the dose at which both terms have the same weight in the abrogation of clonogenic survival. This ratio is known as the aα/β ratio. However, there are plausible scenarios in which the aα/β ratio fails to sufficiently reflect differences between dose-response curves, for example when curves with similar aα/β ratio but different overall steepness are being compared. In such situations, the interpretation of the LQ model is severely limited. Methods: Colony formation assays were performed in order to measure the clonogenic survival of nine human pancreatic cancer cell lines and immortalized human pancreatic ductal epithelial cells upon irradiation at 0-10 Gy. The resulting dataset was subjected to LQ regression and non-linear log-logistic regression. Dimensionality reduction of the data was performed by cluster analysis and principal component analysis. Results: Both the LQ model and the non-linear log-logistic regression model resulted in accurate approximations of the observed dose-response relationships in the dataset of clonogenic survival. However, in contrast to the LQ model the non-linear regression model allowed the discrimination of curves with different overall steepness but similar aα/β ratio and revealed an improved goodness-of-fit. Additionally, the estimated parameters in the non-linear model exhibit a more direct interpretation than the aα/β ratio. Dimensionality reduction of clonogenic survival data by means of cluster analysis was shown to be a useful tool for classifying radioresistant and sensitive cell lines. More quantitatively, principal component analysis allowed the extraction of scores of radioresistance, which displayed significant correlations with the estimated parameters of the regression models. Conclusions: Undoubtedly, LQ regression is a robust method for the analysis of clonogenic survival data. Nevertheless, alternative approaches including non-linear regression and multivariate techniques such as cluster analysis and principal component analysis represent versatile tools for the extraction of parameters and/or scores of the cellular response towards ionizing irradiation with a more intuitive biological interpretation. The latter are highly informative for correlation analyses with other types of data, including functional genomics data that are increasingly being generated.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Clonogenic Survival ; Colony Formation Assays ; Hierarchical Clustering ; Linear-quadratic Model ; Non-linear Regression ; Principal Component Analysis ; Radiotherapy
ISSN (print) / ISBN 1748-717X
e-ISSN 1748-717X
Zeitschrift Radiation Oncology
Quellenangaben Band: 11 Heft: 1, Seiten: , Artikelnummer: 11 Supplement: ,
Verlag BioMed Central
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Translational Metabolic Oncology (IDC-TMO)