title: Compound set enrichment: a novel approach to analysis of primary HTS data.
abstract: The main goal of high-throughput screening (HTS) is to identify active chemical series rather than just individual active compounds. In light of this goal, a new method (called compound set enrichment) to identify active chemical series from primary screening data is proposed. The method employs the scaffold tree compound classification in conjunction with the Kolmogorov-Smirnov statistic to assess the overall activity of a compound scaffold. The application of this method to seven PubChem data sets (containing between 9389 and 263679 molecules) is presented, and the ability of this method to identify compound classes with only weakly active compounds (potentially latent hits) is demonstrated. The analysis presented here shows how methods based on an activity cutoff can distort activity information, leading to the incorrect activity assignment of compound series. These results suggest that this method might have utility in the rational selection of active classes of compounds (and not just individual active compounds) for followup and validation.
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Pharma AG, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland, and 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. thibault.varin@novartis.com
authors.forename: Thibault
authors.initials: T
authors.lastname: Varin
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Gubler
authors.forename: Christian N
authors.initials: CN
authors.lastname: Parker
authors.forename: Ji-Hu
authors.initials: JH
authors.lastname: Zhang
authors.forename: Pichai
authors.initials: P
authors.lastname: Raman
authors.forename: Peter
authors.initials: P
authors.lastname: Ertl
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schuffenhauer
mesh_terms: D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays / Q000379:methods*