My research is focused on the physiologic function of EWSR1. According to the DepMap, EWSR1 is categorized as a common essential gene. Actually, 1071 out of 1086 cell lines show gene effects of around -1.0, strongly suggesting that EWSR1 is an essential gene. However, my EWSR1 conditional KD HCT116 cells using Auxin induced degron system and EWSR1 In-del KO cells made by using the CRISPR SYSTEM show that cells grow OK under the unstressed condition without EWSR1 expression. I also found some publications showing that EWSR1 KO cells and EWSR1 KO mice are viable.
I would just like to know what would possibly make this kind of false evaluation in DepMap, particularly in the case of EWSR1. It seems Not gene copy number problem which could be potentially making false evaluation as common essential.
I’m curious why you would extrapolate your result in a single cell line to say the results in 1000+ other cell lines are wrong?
Can you share all the evidence you have that in your system the EWSR1 protein is gone, i.e. that your degron system was effective and/or that the CRISPR guide(s) you used were effective? How many different guides did you use in your experiment?
One thing to keep in mind is that the readout of the genetic perturbation screens is cell count, not cell death. Since the CRISPR and RNAi screens are several weeks long, multiple cell doublings occur, depending on growth rate, and it can be difficult to differentiate between cases where gene perturbation caused the cells to stop growing and cases where the cells underwent apoptosis (cytostatic vs. cytotoxic effects).
Also, the EWSR1 knockdown using RNAi does not result in pan-dependency, suggesting higher efficacy knockout is required to see strong effects on cell fitness. In other words, the effect could be specific to the type of perturbation.
