Issue with Drug sensitivity AUC (CTD^2)

Issues and Bugs
1

Hi,

I am encountering an issue while downloading the Drug Sensitivity AUC (CTD^2) file from the custom download section. Specifically, the values in the file do not appear to be AUC scores, as they fall outside the expected range of 0 to 1.

Could you please advise where I can access the matrix containing the actual AUC values?

Thank you,
Alessandro

2

Hi Alessandro - can you describe the unexpected values? Are they greater than 1, or negative? If they are greater than 1, that is possible if for example the compound is causing cell growth.

3

The value reported in the Drug Sensitivity AUC (CTD^2) file are positive values grater than 1. However this file should report Area Under the Curve (AUC) values which they typically range from 0 and 1. Correct AUC files are available for the SANGER and PRISM datasets (which I am currently using) but not for CTD. It does not look like the AUC matrix for the CTD dataset has been uploaded. Can you please help me with that?

Thanks!

4

Yep, this is confusing when you first use the CTRP data. The data are the actual AUCs, but it scaled weirdly. In the original CTRP publication from 2013, they decided to scale the AUCs by multiplying the AUC by the maximum dose. I think this was to allow for comparison across drugs because not all drugs were tested at the same dose range. You can undo the scaling by dividing by the maximum drug concentration.

If you are using the AUC data as a continuous variable, you don’t have to undo the scaling though. You can also find recalculated data online as well. I work at the Huang Lab at the University of Minnesota and we refitted the dose response curves and you can find that at our website.

You can find some more information at this post

5

After a bit of investigation of the CTRP data, it does not appear to be true that the AUC values on DepMap are just standard AUC values multiplied by the maximum concentration. Looking at the AUC data on DepMap and taking the maximum AUC for each drug, the values range from 13.574 to 29.350. However, the range of concentrations is from 0.13 - 600 uM. If the AUC data on DepMap was just 0-1 values that were multiplied by the maximum concentration, then the maximum AUCs for each drug should be 1*maximum_concentration. Therefore, the maximum AUC values across the drug should range from 0.13 to 600, not ~13 - 29.

You can even take some examples, CIL56 is listed as having a top testing concentration of 2.5, but the AUC values range from 6.92 to 17.19. Meaning the “original” AUCs would all be 6.92/2.5, which is very much greater that 1.

Finally, a word of caution against using the AUC values that are on DepMap, I have compared the DepMap AUC values with AUC values calculated by other groups who have refit the original CTRP data. It appears that the DepMap CTRP values provided may have a number of values that are greater to 1 and potentially not biologically relevant. The distribution of AUCs from DepMap look very different compared to the recalculated values.