Interpretation of Drug sensitivity AUC and Logfold change value

Q&A
1

Dear Depmap team,

I have some questions regarding how to interpret Drug sensitivity AUC and Logfold change value during compound screening on cell lines:

  1. If cell line A has the higher the drug sensitivity AUC than cell line B on compound C, does it mean that cell line A is more sensitive than cell line B when treated with compound C?
  2. If cell line A has positive higher logfold change value than cell line B on compound C, does it mean that cell line A is more resistant than cell line B when treated with compound C? How about if cell line A has negative logfold change, what does it mean again?

Thank you in advance!

Best,
Marissa

1 Like
2

Hi Marissa,

Higher AUC implies less sensitivity to the compound, similarly higher LFC also implies less sensitivity.

As a reasonable heuristic, you can consider AUC as the average of 2^LFC (i.e. foldchange viabilities) over different doses, so they are (roughly) increase and decrease together.

Warmly,
Mustafa

3

Hi Mustafa,
Thank you very much for the answer!
Best,
Marissa

4

Hi Mustafa,

To follow up the question above, what is the LFC measured by? cell number in treatment group compared to DMSO group?

Thanks,
Marissa

5

Yes, it is the log2 of the ratio of abundance of cells in treatment group vs the ones in the control (DMSO) group.

6

I want to learn about the first question of @Marissa

My understanding is
“if cell line A has a higher drug sensitivity AUC (Area Under the Curve) than cell line B when treated with compound C, it means that cell line A is more sensitive to the effects of compound C compared to cell line B.” I thought higher AUC correlates with a stronger or more significant response to compound C? Best,
Amare

7

Hi Amare,

Unfortunately, that’s not true AUC value is proportional to the viability level, therefore it is inversely proportional to the sensitivity.

AUC values typically change between 0 and 1, and a higher value implies the dose-response curve is closer to the y = 1 curve (i.e. inert).

8

Hi, is it expected that the auc values are quite often above 1.0? I am working on the “secondary-screen-dose-response-curve-parameters.csv” and 32% of values are above 1.0.

Help is veryy much appreciated!

9

Dear Mustafa_Kocak:
Is an AUC value greater than 1 meaningful? Can it be used for deep learning modeling? Because I believe an AUC value greater than 1 suggests that the drug cannot inhibit the corresponding cell line.

Looking forward to your reply.

Best regards,
Mag