Thanks to Mads, Simon, and Steve.

In summary:

- extreme variance within group (zero or large value) is not a good sign, and experimental issues are to be suspected - pooling (summing) tags over reference transcripts can rescue some of the signal - DESeq, and to some extent edgeR, will report as differentially expressed such gene/tags with such pathological counts while they should not. The issue is acknowledged and care should be taken (here we use various visualizations to complement the p-values).




Laurent

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