Precision multidimensional assay for high-throughput microRNA drug discovery
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 528785249 | ||
| 005 | 20190713030951.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924s2016 xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000113652 |2 doi |
| 024 | 7 | 0 | |a 10.1038/ncomms10709 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/113652 | ||
| 245 | 0 | 0 | |a Precision multidimensional assay for high-throughput microRNA drug discovery |h [Elektronische Daten] |c [Benjamin Haefliger, Laura Prochazka, Bartolomeo Angelici, Yaakov Benenson] |
| 246 | 0 | |a Nat Commun | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a 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. | |
| 540 | |a Creative Commons Attribution 4.0 International |u http://creativecommons.org/licenses/by/4.0 |2 ethresearch | ||
| 700 | 1 | |a Haefliger |D Benjamin |e joint author | |
| 700 | 1 | |a Prochazka |D Laura |e joint author | |
| 700 | 1 | |a Angelici |D Bartolomeo |e joint author | |
| 700 | 1 | |a Benenson |D Yaakov |e joint author | |
| 773 | 0 | |t Nature Communications |d London : Nature Publishing Group |g 7, p. 10709 |x 2041-1723 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/113652 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/113652 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Haefliger |D Benjamin |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Prochazka |D Laura |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Angelici |D Bartolomeo |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Benenson |D Yaakov |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t Nature Communications |d London : Nature Publishing Group |g 7, p. 10709 |x 2041-1723 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||