Originally posted by zhengz
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Simon
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Not really. A lot of people assume a Poisson distribution (implicitly, by using Fisher's exact test) and then, for genes with high count rates, everything looks significant. You simply need to assess the biological variance (and for few replicates, you can only do so by pooling information over genes) and add it to the shot noise from the Poisson. NB is certainly the simplest way to to that.
Simon
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