Question about the dependency on two genes

Q&A
1

We are interested in the DEMETER score data from RNAi screening or alike in URL: https://depmap.org/portal/achilles/, which is essentially the dependency of each gene in cell lines if my understanding is correct.

I have a question on the DEMETER scores. These scores assigned to each gene and each cell line based on corresponding experiment. However, we are interested in dependency of two genes for the same cell line, say KRAS and NF1 etc. From your database, We can get individual DEMETER scores for either KRAS or NF1 for our interested cell lines, but For dependency on both genes (or interaction of the two genes) for the same cell line, is there any strategy or way to derive or infer based on the individual DEMETER scores of both individual genes? Any idea or insight on that how to do it? Since these scores are derived based on experiments testing on each gene individually, for the interaction between them or dependency on both genes, could these individual scores provide some clues at least? Say, if a cell line depends on both genes based on their DEMETER scores, does this mean the cell would depend on both genes as well as their interaction? For drugs, we can have synergy effect, what about the DEMETER scores?

Thanks a lot for your help in advance!!

Best
Ming

2

I don’t believe the scores themselves give you information about their interactions. However, I believe I’ve seen papers from people outside of the DepMap project where they have performed double knockouts in some model lines to assess genetic interactions – which sounds like what you are looking for.

One key difference between those data and what you’ll find in the DepMap, is that the DepMap data covers a wide range of genetic backgrounds and cellular contexts by screening hundreds of cell lines. Whereas, I believe the double knockout data I’ve heard of was generated by screening one or two cell lines. Regardless, those experiments seem more aligned with the sort of questions that you seemed to be asking, so perhaps it’s worth exploring those.

3

Thanks a lot for your input and info! Too bad we can not infer anything about the interaction or at least co-dependency of the two genes from their individual dependency, I thought there might be a way to do that. You mentioned: someone performed double knockouts in some model lines to assess genetic interactions, do you have references on that? Thx again!