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Precision multidimensional assay for high-throughput microRNA drug discovery.

ABSTRACT: 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.

SUBMITTER: Haefliger B

PROVIDER: S-EPMC4757758 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Precision multidimensional assay for high-throughput microRNA drug discovery.

Haefliger Benjamin B Prochazka Laura L Angelici Bartolomeo B Benenson Yaakov Y

Nature communications 20160216

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 ...[more]

PMID: 26880188

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Dataset Information

Precision multidimensional assay for high-throughput microRNA drug discovery.

Publications

Precision multidimensional assay for high-throughput microRNA drug discovery.

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