An economic framework to prioritize confirmatory tests after a high-throughput screen.
How many hits from a high-throughput screen should be sent for confirmatory experiments? Analytical answers to this question are derived from statistics alone and aim to fix, for example, the false discovery rate at a predetermined tolerance. These methods, however, neglect local economic context and consequently lead to irrational experimental strategies. In contrast, the authors argue that this question is essentially economic, not statistical, and is amenable to an economic analysis that admits an optimal solution. This solution, in turn, suggests a novel tool for deciding the number of hits to confirm and the marginal cost of discovery, which meaningfully quantifies the local economic trade-off between true and false positives, yielding an economically optimal experimental strategy. Validated with retrospective simulations and prospective experiments, this strategy identified 157 additional actives that had been erroneously labeled inactive in at least one real-world screening experiment.
Swamidass
S Joshua
SJ
Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. jswamidass@path.wustl.edu
Bittker
Joshua A
JA
Bodycombe
Nicole E
NE
Ryder
Sean P
SP
Clemons
Paul A
PA
D005189:False Positive Reactions; D005240:Feasibility Studies; D057166:High-Throughput Screening Assays / Q000191:economics* / Q000379:methods*; D006801:Humans; D015203:Reproducibility of Results