Many of the early RNA-seq datasets involve sequence reads from technical replicates (e.g. same source of RNA) as opposed to biological replicates (e.g. RNA from different individuals). Technical replicates will generally have lower variability than biological replicates and in our experience, the dispersion parameter (and the moderation procedure in edgeR) may not be necessary. For experiments with technical replicates, the data may be fitted well by the Poisson distribution, as demonstrated in Marioni et al. (2008). Since the Poisson distribution is a special case of the NB distribution (ϕ=0), edgeR can perform a Poisson-based analysis. The pairwise exact testing procedure will still be useful for these datasets.