title: Extracting SAR Information from a Large Collection of Anti-Malarial Screening Hits by NSG-SPT Analysis.
abstract: We combine two graphical SAR analysis methods, Network-like Similarity Graphs (NSGs) and Similarity-Potency Trees (SPTs), to search for SAR information in a large and heterogeneous compound data set containing more than 13,000 antimalarial screening hits that was recently released by GlaxoSmithKline (GSK). The NSG-SPT approach first identifies subsets of compounds inducing local SAR discontinuity in data sets and then extracts available SAR information from these subsets in a graphically intuitive manner. Applying the NSG-SPT analysis scheme, we have identified in the GSK collection compound subsets of high local SAR information content including both known and previously unknown antimalarial chemotypes, which yielded interpretable SAR patterns. This information should be helpful to prioritize and select antimalarial candidate compounds for further chemical exploration. Furthermore, the NSG-SPT tools are publicly available, and our study also shows how to practically apply these SAR analysis methods to study large compound data sets.
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität , Dahlmannstrasse 2, D-53113 Bonn, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Wawer
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität , Dahlmannstrasse 2, D-53113 Bonn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
keywords: Anti-malaria screening hits; data mining; graphical SAR analysis; network-like similarity graphs; similarity-potency trees; structure−activity relationship (SAR) information