I am using DESeq2 to analyse RNA-seq data and very appreciated its comprehensive functionality. In my data, the counts are affected by genotype and cell type. I think there is interaction between genotype and cell type. Therefore, interaction term should be considered. In the help pages of function "results", there are two options for doing this. One is adding the interaction term explicitly in the formula, the other is combing two factors into one factor named group. I run the examples provided in the help page and found that two options output different results. For example, log2 fold change are different. So, what's reason or rationale underlying this situation?
If you run DESeq2 with an interaction term in the design formula, the beta-shrinkage is turned off, i.e. the fold changes are not shrunken. This is also mentioned in the examples section of the results:
# design with interactions terms by default have betaPrior=FALSE
However, if you take your two factors and combine them into a group vector, the beta-shrinkage is performed, leading to different fold change estimates. See also section 3.3. of the vignette for a thorough discussion of this.