Standardized Drug Activity Evaluation

Drug activity levels expressed as 50% growth inhibitory levels (GI50s) are determined by the Developmental Therapeutics Program² at 48 hours using the sulphorhodamine B assay (22 (link)). Repeat experiments must pass quality control criteria, similar to those for gene transcript levels. Experiments with range less than 1.2 log₁₀ or with information on less than 35 cell lines are dropped. This serves to eliminate non-responsive and out of proper range data. The number of experiments that pass these criteria is determined, and 25% of that number calculated (keeping a minimum of 2 and a maximum of 122). Pearson’s correlations are determined for all remaining possible experiment/experiment combinations. Experiments whose average correlations are less than 0.334 (p<0.05 for the 35 cell line minimum in the absence of multiple comparisons correction) and were not correlated to individual probes at ≥ 0.334 are dropped. For the remaining experiments with average correlations less than 0.60 (p<0.00014 for the 35 cell line minimum), the lowest is dropped, and the correlations recalculated for all remaining possible experiment/experiment combinations. Experiments are dropped in this fashion until either all are ≥ to 0.60, or the 25% (of experiments that passed the 1.2 log₂ range criteria) level is reached. This ensures significant pattern match across experiments. Drugs with only one experiment, but pass that the ≤1.2 log₁₀ range test are included as output as they are potentially informative, but must be considered less reliable. For the purpose of this manuscript, compounds that have not yet undergone clinical trials will sometimes be referred to as drugs, as well as those that have.