I couldn’t help but notice that the DepMap CRISPR KO score is assigned for SRY gene in cell lines originating from women. Presumably, most of them have no Y chromosome where SRY is localized.
ACH-000001, female, ovarian
ACH-000019, female, breast
ACH-000023, female, pancreatic
ACH-000024, female, B-cell
… and so on.
Overall, 44% of cell lines with reported SRY KO scores originated from female patients.
We report gene effect scores for all genes which are targeted by the CRISPR library regardless of whether the gene is present (or expressed at all in the given model).
Perhaps a more accurate description of gene effect is that it is a score which describes the viability defect from an attempt to knock out the gene. In these high throughput screens there is no verification that the gene was successfully knocked out.
We don’t make any effort to censor gene effect based on knowledge of the genetics of the model.
It would be surprising if we did observe a viability defect from targeting a gene that we know shouldn’t be there, so I looked at the distribution of gene effects for this gene:
This gene looks to me like it is non-essential in both male and female samples. The distribution of gene effect from knocking out an essential gene is centered at -1 and the distribution of gene effects from knocking out non-essential genes is centered at 0.
This specific gene doesn’t have any gene effects approaching -1, so it seems to be non-essential in all of the screened models, so I don’t see anything surprising about the gene effect of attempting to knockout this gene in the models derived from female patients.
In theory, it could be nice to assume that it is transparent reporting. But in practice, SRY positive scores are quite similar to PTEN. I suspect that for PTEN the forum story would be “well, this is an oncosuppressor.” But now, because of the pseudo-positive SRY effect in cell lines not having SRY, what does it tell about PTEN?
Also, can you please comment on why the average score is ~0.3 for having gRNA targeting a non-existing sequence? Should this value be the reference for neutral effect?
The third question is: Why was the SRY score excluded for most of the cell lines? Only 310 of them have the score. I am trying to understand how to interpret the DepMap results and what the potential source of noise in the data is.
To summarize, under the assumption of completely unsupervised reporting and well-gauged proliferation effect, I would expect SRY scores to be lower than PTEN scores, centered at zero, and reported for every cell line. Instead, the scores are reported for only 310 cell lines, the average score is ~0.3 in female cell lines, and median values of SRY and PTEN are on par.
