I have a set of RNASeq data for various points of a differentiation time series, with replicates. A known fraction of the cells in each sample are MEFs, and 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 (for example) or using svaseq but I can't figure out how. Can anyone recommend a strategy for doing this?
EDITED TO ADD: To clarify, this is a mouse cell line differentiation series that is contaminated by Mouse Embryonic Fibroblasts. As the contaminating MEF mRNA are the same species as the differentiating cell mRNA I can't remove them based on species mapping.