title: Utility-aware screening with clique-oriented prioritization.
abstract: Most methods of deciding which hits from a screen to send for confirmatory testing assume that all confirmed actives are equally valuable and aim only to maximize the number of confirmed hits. In contrast, "utility-aware" methods are informed by models of screeners' preferences and can increase the rate at which the useful information is discovered. Clique-oriented prioritization (COP) extends a recently proposed economic framework and aims--by changing which hits are sent for confirmatory testing--to maximize the number of scaffolds with at least two confirmed active examples. In both retrospective and prospective experiments, COP enables accurate predictions of the number of clique discoveries in a batch of confirmatory experiments and improves the rate of clique discovery by more than 3-fold. In contrast, other similarity-based methods like ontology-based pattern identification (OPI) and local hit-rate analysis (LHR) reduce the rate of scaffold discovery by about half. The utility-aware algorithm used to implement COP is general enough to implement several other important models of screener preferences.
authors: Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA. swamidass@wustl.edu
authors: S Joshua
authors: SJ
authors: Swamidass
authors: Bradley T
authors: BT
authors: Calhoun
authors: Joshua A
authors: JA
authors: Bittker
authors: Nicole E
authors: NE
authors: Bodycombe
authors: Paul A
authors: PA
authors: Clemons
mesh_terms: D000465:Algorithms; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors* / Q000737:chemistry; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D054852:Small Molecule Libraries
chemical_list: D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; C410587:MEX-5 protein, C elegans; D054852:Small Molecule Libraries; D056484:Jumonji Domain-Containing Histone Demethylases; C494424:KDM4A protein, human