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Toward performance-diverse small-molecule libraries for cell-based phenotypic screening using multiplexed high-dimensional profiling

2014; National Academy of Sciences; Volume: 111; Issue: 30 Linguagem: Inglês

10.1073/pnas.1410933111

1091-6490

Mathias J. Wawer, Kejie Li, Sigrun Gustafsdottir, Vebjorn Ljosa, Nicole E. Bodycombe, Melissa A. Marton, Katherine L Sokolnicki, Mark‐Anthony Bray, Melissa M. Kemp, Ellen Winchester, Bradley R Taylor, George Grant, C. Suk-Yee Hon, Jeremy R. Duvall, Joshua Wilson, Joshua A. Bittker, Vlado Dančík, Rajiv Narayan, Aravind Subramanian, Wendy Winckler, Todd R. Golub, Anne E. Carpenter, Alykhan F. Shamji, Stuart L. Schreiber, Paul A. Clemons,

Viral Infectious Diseases and Gene Expression in Insects

Significance A large compound screening collection is usually constructed to be tested in many distinct assays, each one designed to find modulators of a different biological process. However, it is generally not known to what extent a compound collection actually contains molecules with distinct biological effects (or even any effect) until it has been tested for a couple of years. This study explores a cost-effective way of rapidly assessing the biological performance diversity of a screening collection in a single assay. By simultaneously measuring a large number of cellular features, unbiased profiling assays can distinguish compound effects with high resolution and thus measure performance diversity. We show that this approach could be used as a filtering strategy to build effective screening collections.