Viability at a given dosage from AUC

For PRISM 19Q4, secondary screen, I am wondering if we can compute % killing at a required dosage from AUC values. For each drug-cell line pair, we have available fitted curve upper/lower limits & slope.

If I am not mistaken, these two formulas from Corsello et al. 2020 could be the starting points, but am not sure about the next steps as not all variables (eg. E-inf) here are completely clear. Thanks! Screen Shot 2020-12-26 at 10.54.22 PM
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Hello,

I believe your comment is totally correct, we can essentially “impute” the missing doses using the dose-response parameters we computed.

To do that you should download “secondary-dose-response-curve-parameters.csv” file and use “lower_limit” column as the E_infty parameter in the equations.

However, for a simpler solution one can just take replicate level log-fold change data and fit a line using the available data for the closest 2 doses (one above and one below the targeted dose - in total ~6 data points: 2 doses x 3 replicates) to approximate the final result. This will help you with the missing dose response parameters (i.e. poor dose response curve fits), and would be easier to track.

Warmly,
Mustafa

For PRISM 19Q4, secondary screen, I am wondering if we can compute % killing at a required dosage from AUC* values. Returns the AUC (Area Under the drug response Curve) given concentration slope unblocked and viability as input, normalized by the concentration range of the experiment. For Sanger, the choices are: AUC – the area under the fitted dose response curve; … at which the compound reaches 50% reduction in cell viability. AUC , a parameter that combines potency and efficacy into a single measure was robust as a response metric when the goal was to compare