One sensible solution is to share information across genes. In DESeq2, we assume that genes of similar average expression strength have similar dispersion. We here explain the concepts of our approach using as examples a dataset by Bottomly et al. [16] with RNA-seq data for mice of two different strains and a dataset by Pickrell et al. [17] with RNA-seq data for human lymphoblastoid cell lines. For the mathematical details, see Materials and methods.