Second, the method of Watanabe et al. corrects for the average expression of all cell types in a dataset. This practice is, in our view, problematic as it necessarily forces dependence on the composition of a scRNA-seq dataset. For instance, if a dataset consists mostly of neurons, this amounts to correcting for neuronal expression and necessarily erodes power to detect trait enrichment in neurons. Alternatively, if a dataset is composed mostly of non-neuronal cells, this will impacts the detection of enrichment in non-neuronal cells.
