[BioC] Dose-Response: Regressiion and ANOVA

[Arne.Muller at aventis.com]

Dear All,

I'm interested in your experience of analyzing dose-response experiments. I've an unbalanced design with 3 studies and within each study 4 to 5 doses of a drug (the doses do not exactmy the same in each study).

Usually I run an anova per gene

anova(lm(Intensity ~ Study + Dose + Study:Dose))

where Study and Dose are factors, and for the linear model I use a treatment contrast with the control dose (no treatment) as the base.

Actually I'm realy interested in a dose-response, i.e. consistent down- or up-regulation of a gene by dose. I have turned the Dose factor into a continous variable and taken the log10 of the dose. The model formular stays the same as above.

For the factorial desgin I get 112 genes a with significant dose effect, and for the regression model (dose is the regressor and study stays a factor) I get 280 genes at the same significance level.

Can I conclude that the regression model is more sensitive? Is there a way to find out where the differences come from and why there are so many differences?

There a strong difference using un-transformed or log transformed values for dose, and since the control dose is 0.0mM which value to add for the log transformation. Are any rules of thumb for the value to add?

I'd be happy to read about your experience of analyzing dose-response experiments and whether you use a factorial or regression desgin.

	kind regards,

	Arne