Systematic Identification of Pharmacological Targets from Small-Molecule Phenotypic Screens

Liu, Xueping; Baarsma, Hoeke Abele; Thiam, Chung Hwee; Montrone, Corinna; Brauner, Barbara; Fobo, Gisela; Heier, Julia-Sophie; Duscha, Sven; Königshoff, Melanie; Angeli, Veronique; Ruepp, Andreas und Campillos, Monica (2016): Systematic Identification of Pharmacological Targets from Small-Molecule Phenotypic Screens. In: Cell Chemical Biology, Bd. 23, Nr. 10: S. 1302-1313

Abstract

Phenotypic drug discovery offers some advantages over target-based methods, mainly because it allows drug leads to be tested in systems that more closely model distinct disease states. However, a potential disadvantage is the difficulty of linking the observed phenotype to a specific cellular target. To address this problem, we developed DePick, a computational target de-convolution tool to determine targets specifically linked to small-molecule phenotypic screens. We applied DePick to eight publicly available screens and predicted 59 drug target-phenotype associations. In addition to literature-based evidence for our predictions, we provide experimental support for seven predicted associations. Interestingly, our analysis led to the discovery of a previously unrecognized connection between the Wnt signaling pathway and an aromatase, CYP19A1. These results demonstrate that the DePick approach can not only accelerate target de-convolution but also aid in discovery of new functionally relevant biological relationships.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2451-9448
• Sprache: Englisch