Two exceptions to the default DESeq2 LFC estimation steps are used for experimental designs with interaction terms. First, when any interaction terms are included in the design, the LFC prior width for main effect terms is not estimated from the data, but set to a wide value (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} ${\sigma ^{2}_{r}} = (\log (2))^{2} \, 1000$ \end{document}σr2=(log(2))21000, or 1000 on the base 2 scale). This ensures that shrinkage of main effect terms will not result in false positive calls of significance for interactions. Second, when interaction terms are included and all factors have two levels, then standard design matrices are used rather than expanded model matrices, such that only a single term is used to test the null hypothesis that a combination of two effects is merely additive in the logarithmic scale.
