the DESeq2 framework as gene- and sample-specific normalization factors. In addition, the approach used in DESeq2 can be extended to isoform-specific analysis, either through generalized linear modeling at the exon level with a gene-specific mean as in the DEXSeq package [30] or through counting evidence for alternative isoforms in splice graphs [31,32]. In fact, the latest release version of DEXSeq now uses DESeq2 as its inferential engine and so offers shrinkage estimation of dispersion and effect sizes for an exon-level analysis, too.