I have a set of Mouse RNASeq data for various points of a differentiation time series, with replicates. A known fraction of the cells in each sample are Mouse Embryonic Fibroblasts (MEFs), that fraction varies quite a bit per sample. I have expression data for a pure MEF sample grown under similar conditions.
I'd like to do a fold change analysis between time points, subtracting the MEF expression contamination in such a way that the resulting increased variance per gene is factored into the fold change analysis.
It seems it may be possible to do it within DESeq2 or using svaseq but I can't figure out how. Can anyone recommend a strategy for doing this; I'm really not clear on how to approach it.
(note this is a crosspost from Biostars, as I wasn't able to get a solution there)