caa a22 4500 528785249 20190713030951.0 cr unu---uuuuu 180924s2016 xx s 000 0 eng 10.3929/ethz-b-000113652 doi 10.1038/ncomms10709 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/113652 Precision multidimensional assay for high-throughput microRNA drug discovery [Elektronische Daten] [Benjamin Haefliger, Laura Prochazka, Bartolomeo Angelici, Yaakov Benenson] Nat Commun Open access ethresearch Development of drug discovery assays that combine high content with throughput is challenging. Information-processing gene networks can address this challenge by integrating multiple potential targets of drug candidates' activities into a small number of informative readouts, reporting simultaneously on specific and non-specific effects. Here we show a family of networks implementing this concept in a cell-based drug discovery assay for miRNA drug targets. The networks comprise multiple modules reporting on specific effects towards an intended miRNA target, together with non-specific effects on gene expression, off-target miRNAs and RNA interference pathway. We validate the assays using known perturbations of on- and off-target miRNAs, and evaluate an ∼700 compound library in an automated screen with a follow-up on specific and non-specific hits. We further customize and validate assays for additional drug targets and non-specific inputs. Our study offers a novel framework for precision drug discovery assays applicable to diverse target families. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Haefliger Benjamin joint author Prochazka Laura joint author Angelici Bartolomeo joint author Benenson Yaakov joint author Nature Communications London : Nature Publishing Group 7, p. 10709 2041-1723 http://hdl.handle.net/20.500.11850/113652 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/113652 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Haefliger Benjamin joint author ETHRESEARCH 700 1- Prochazka Laura joint author ETHRESEARCH 700 1- Angelici Bartolomeo joint author ETHRESEARCH 700 1- Benenson Yaakov joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 7, p. 10709 2041-1723 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access