We ran DESeq2 on an experiment with several samples (each sample in triplicates). The samples differ dramatically. In one of the pair wise comparisons, we have ~4200 differentially expressed genes (with fold change above 2 or below -2, p-adj<0.05), out of ~19,000 detected genes (human genome).
DESeq normalization is based on the assumption that most genes are not differentially expressed.
Do you think that it is valid to use this normalization in this case?