1. Large Row-Constrained Supersaturated Designs for High-throughput Screening
- Author
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Smucker, Byran J., Wright, Stephen E., Williams, Isaac, Page, Richard C., Kiss, Andor J., Silwal, Surendra Bikram, Weese, Maria, and Edwards, David J.
- Subjects
Statistics - Methodology ,Statistics - Applications - Abstract
High-throughput screening, in which multiwell plates are used to test large numbers of compounds against specific targets, is widely used across many areas of the biological sciences and most prominently in drug discovery. We propose a statistically principled approach to these screening experiments, using the machinery of supersaturated designs and the Lasso. To accommodate limitations on the number of biological entities that can be applied to a single microplate well, we present a new class of row-constrained supersaturated designs. We develop a computational procedure to construct these designs, provide some initial lower bounds on the average squared off-diagonal values of their main-effects information matrix, and study the impact of the constraint on design quality. We also show via simulation that the proposed constrained row screening method is statistically superior to existing methods and demonstrate the use of the new methodology on a real drug-discovery system., Comment: Supplementary materials can be found at https://sites.miamioh.edu/byran-smucker/research-2/
- Published
- 2024