Large, Row-Constrained Supersaturated Designs for High-Throughput Screening

Music City Center 

High-throughput screening, in which large numbers of compounds are traditionally studied one-at-a-time in multiwell plates, is widely used across many areas of the biological and chemical sciences including drug discovery. To improve the efficiency of these screens, we propose a new class of supersaturated designs that guide the construction of pools of compounds in each well. Because the size of the pools are typically limited by the particular application, the new designs accommodate this constraint and are part of a larger procedure that we call Constrained Row Screening, or CRowS. We introduce the designs and their construction, and study their behavior as a function of the constraint. Via simulation, we show that CRowS is statistically superior to the traditional one-compound-one-well approach as well as an existing pooling method, and as time permits provide results from two separate applications, both related to the search for solutions to antibiotic-resistant bacteria.

drug discovery

screening

experimental design

Lasso 

Section on Physical and Engineering Sciences