TY - JOUR
T1 - An economic framework to prioritize confirmatory tests after a high-throughput screen
AU - Swamidass, S. Joshua
AU - Bittker, Joshua A.
AU - Bodycombe, Nicole E.
AU - Ryder, Sean P.
AU - Clemons, Paul A.
N1 - Funding Information:
We thank the Physician Scientist Training Program of the Washington University Pathology Department for supporting SJS; NEB and PAC are supported in part by NCI’s Initiative for Chemical Genetics (N01-CO-12400) and NIH Molecular Libraries Network (U54-HG005032), and SPR is supported by the NIH (NS-059380). We also thank Paul Swamidass and Richard Ahn for their helpful comments on the manuscript.
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - automation/robotics
KW - chemoinformatics
KW - data analysis software
KW - fluorescence polarization (FP)
KW - information management
UR - http://www.scopus.com/inward/record.url?scp=77955830685&partnerID=8YFLogxK
U2 - 10.1177/1087057110372803
DO - 10.1177/1087057110372803
M3 - Article
C2 - 20547534
AN - SCOPUS:77955830685
SN - 1087-0571
VL - 15
SP - 680
EP - 686
JO - Journal of Biomolecular Screening
JF - Journal of Biomolecular Screening
IS - 6
ER -