Is there a threshold in Drug Sensitivity AUC, below which it is considered that the drug has an impact on cell line proliferation? which threshold?
Similarly, does a threshold also exist in the PRISM Repurposing Primary Screen dataset?
Hi,
For the Primary screen, the values are log2(Viabilities) at 2.5uM, and historically, we considered 30% viability (corresponding to log2(0.3) =~ -1.74 as a “sensitivity threshold.”
For AUC, it is trickier since it is also a function of the dose range screened for the drug. I don’t know the particular analysis you are following, but my recommendation would be scaling AUCs (maybe z-scores) and treating cell lines on the left tail (maybe z < -2) as sensitive lines.
Are we certain this is correct? The DepMap paper states “We label cell lines as sensitive to a treatment if the median-collapsed fold-change is less than 0.3.”
Thus, it appears that the binary cutoff is actually log2(0.3), which is 1.23. Meaning that a 23% increase in cell line proliferation relative to the control. I am unclear why an increase relative to the control would be considered sensitive to the treatment, although I think I read about noise being an issue.
If the metric were indicating 30% viability, the wording should state this, and not specifically mention “median-collapsed fold-change is less than 0.3.”
Can I get a clarification from the Depmap team on this important point?
Thanks
Apologies, I of course meant that since a “median-collapsed log-fold change” of 0.3 is the value reported, which itself is log2(1.23). So according to the paper, the reported value of 0.3 used as a threshold would correspond to cell proliferation relative to DSMO of 1.23, ie. a 23% increase.
Can someone from the DepMap team please clarify this?
