CellOracle KO simulation produced results opposite to real KO results
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Sustella commented
Thanks so much for the wonderful package for studying cell differentiation through regulator gene perturbation simulation.
From the literature, Isl1 plays a very important role in differentiating a progenitor cell A into a descendant cell B, i.e. when Isl1 is knocked out, cell A stops differentiating to cell B. Isl1 expression value decreases when differentiating to the descendant cell. When Isl1 KO is simulated in CellOracle, cell identity still shifts from A to B; if Isl1 expression value was set to 5, cell identity shifted from B to A. The results are different from real KO results.
I would like to confirm with you what I did is correct.
- The input data I have is after applying the normalizedata() function from Seurat. Before using CellOracle, I applied math.expm1() to revert the effect of log1p(). Since I don't have the original raw data, would this work?
- Since I have cell type annotation, I do Isl1 KO simulation for all the cell populations of the progenitor cell A and descendant cell B, instead of sub-regions of cell A and cell B from clustering. Is it OK?
- From the results of the CellOracle paper, it seems that all "differentiation inhibited" KO results occur in the input data where regulator expression value increases when differentiating to a descendant cell. In my data, it is the opposite.
Appreciate your feedback.