According to our simulations (Figure 2), including these 53 categories in our baseline model allows us to obtain unbiased or nearly unbiased estimates of enrichment for a wide range of potential new categories. To estimate the enrichment of a new annotation, we perform analyses using a model with these 53 annoations plus the new annotation. For example, for the cell-type-specific analysis, we add each cell-type-specific annotation to the baseline model one at a time, and asses enrichment using the z-score of the cell-type-specific annotation.
