Dear Oliver,

	In addition to Limma, which measures changes between conditions,
the program EDGE is useful for time course analysis
to measure statistical significance of changes over the entire time course. You
can read about here

http://www.ncbi.nlm.nih.gov/pubmed/16357033
http://www.ncbi.nlm.nih.gov/pubmed/16141318

With hopes that this helps,
Rich

Richard A. Friedman, PhD
Associate Research Scientist,
Biomedical Informatics Shared Resource
Herbert Irving Comprehensive Cancer Center (HICCC)
Lecturer,
Department of Biomedical Informatics (DBMI)
Educational Coordinator,
Center for Computational Biology and Bioinformatics (C2B2)/
National Center for Multiscale Analysis of Genomic Networks (MAGNet)/
Columbia Initiative in Systems Biology
Room 824
Irving Cancer Research Center
Columbia University
1130 St. Nicholas Ave
New York, NY 10032
(212)851-4765 (voice)
friedman@cancercenter.columbia.edu
http://cancercenter.columbia.edu/~friedman/

"Complex numbers! Ha! Ha! There is nothing weirder
than imaginary numbers. Architects don't need to know 
complex numbers. Whenever I get a  negative root for
an area, I throw it out. And don't talk to me about
quaternions. I am not going into computer animation."
-Rose Friedman, age 16
 

On Jan 16, 2013, at 6:05 PM, Oliver Hofmann wrote:

> Dear all,
> 
> 
> posting this on behalf of a colleague who is looking for help with a time series analysis:
> 
> "I've read a number of articles and searched the list's archive, but cannot figure out what is the best method to analyze time course data where I need to adjust for confounders.
> 
> First - my experiment: Longitudinal cohort study in 80 children (60 asthmatics and 20 non-asthmatics), three time points (one prior to exposure, two after exposure), one exposure (endotoxin) and several measured confounders (other allergens, asthma vs. no asthma, atopy vs. no atopy).
> 
> The research question is:
> 
> 1) Are there differentially expressed genes in response to endotoxin at the two time points after exposure (early and late) - note issue of confounding exposures
> 
> 2) Do differentially expressed genes differ between asthmatics and non-asthmatics at the two time points in response to endotoxin exposure
> 
> Most time course studies are laboratory studies where by experimental design there are no (known) confounders.  Limma or a linear mixed effect model seem to handle time course with covariates.
> 
> Can anybody give me advice on:
> 
> 1. What is the best method (limma vs. linear mixed effect model vs. other) for this research question and design, and _why?
> 
> 2. What is the best way to decide which covariates to include (prior biological knowledge vs. algorithm)
> 
> 3. How does one typically handle missing data in this kind of time course microarray studies?"
> 
> Any feedback would be appreciated!
> 
> Best, Oliver
> 
> 
> -- 
> Research Scientist    Harvard School of Public Health
> Associate Director    Bioinformatics Core
> Skype: ohofmann       Phone: +1 (617) 365 0984
> http://compbio.sph.harvard.edu/chb/
> 
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