I have two scRNA-seq datasets, both derived from a heterogeneous population of cells (comprising similar numbers of cell types and subpopulations). One sample has been treated with a drug, the other has not. While I can separate out the cellular subpopulations in each dataset, what I want is to then identify differentially expressed genes that result from the drug treatment - in each of the individual cellular subpopulations.
In theory I can do this by extracting average transcript counts for each gene and then use a program such a Gfold to run a differential expression analysis by treating each dataset as a bulk-rnaseq experiment. However this doesn't seem very elegant, and more importantly does not take into account the distribution of transcript counts for a given gene in a given subpopulation.
Are there any packages out there designed for these types of analyses? Does anyone have any thoughts on how I might approach this otherwise?