Dear Gordon,

On 12/10/2012 11:06 PM, Gordon K Smyth wrote:
I don't see a proposal below, only a question.

Yes, I ended up not really proposing anything because I realized that I didn't really have anything that improves on linear modeling. But see below for what I was trying to get at.

What linear modelling programs such as limma and edgeR do is not "simply computing logCPM individually for each sample and taking the mean of all the samples in each group".
This what I thought, and I just wanted to make sure. Which brings me to...
I think that it might be better for you to try to understand what linear modelling is doing in a more sophisticated and complete manner before trying to redesign the process. What about reading a textbook on linear modelling?
This is exactly what I will do.

However, I want to clarify that I'm not trying to redesign the process of linear modeling. I'm trying to find a middle ground between simple but inflexible two-group comparisons and flexible but confusing (for biologists that I work with, and sometimes for me) linear modeling in its full generality. I think my idea of a no-intercept factor of interest plus sum-to-zero blocking factors accomplishes that goal for my purposes. It is a subset of the full possibilities of (generalized) linear modelling, but one which (unlike simple two-group comparisons) encompasses every experimental design I've encountered with so far, and does so in a way that makes sense to my biologist collaborators, since each group mean gets its own coefficient in the design matrix.

Thank you, Gordon, for your patience with me as I stumble around with my limited understanding of linear modelling. I will try to find a good textbook on the subject and improve my understanding.

Sincerely,

-Ryan

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