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Gene-signature-derived IC50s/EC50s reflect the potency of causative upstream targets and downstream phenotypes.

ABSTRACT: Multiplexed gene-signature-based phenotypic assays are increasingly used for the identification and profiling of small molecule-tool compounds and drugs. Here we introduce a method (provided as R-package) for the quantification of the dose-response potency of a gene-signature as EC50 and IC50 values. Two signaling pathways were used as models to validate our methods: beta-adrenergic agonistic activity on cAMP generation (dedicated dataset generated for this study) and EGFR inhibitory effect on cancer cell viability. In both cases, potencies derived from multi-gene expression data were highly correlated with orthogonal potencies derived from cAMP and cell growth readouts, and superior to potencies derived from single individual genes. Based on our results we propose gene-signature potencies as a novel valid alternative for the quantitative prioritization, optimization and development of novel drugs.

SUBMITTER: Renner S

PROVIDER: S-EPMC7295968 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Gene-signature-derived IC50s/EC50s reflect the potency of causative upstream targets and downstream phenotypes.

Renner Steffen S Bergsdorf Christian C Bouhelal Rochdi R Koziczak-Holbro Magdalena M Amati Andrea Marco AM Techer-Etienne Valerie V Flotte Ludivine L Reymann Nicole N Kapur Karen K Hoersch Sebastian S Oakeley Edward James EJ Schuffenhauer Ansgar A Gubler Hanspeter H Lounkine Eugen E Farmer Pierre P

Scientific reports 20200615 1

Multiplexed gene-signature-based phenotypic assays are increasingly used for the identification and profiling of small molecule-tool compounds and drugs. Here we introduce a method (provided as R-package) for the quantification of the dose-response potency of a gene-signature as EC50 and IC50 values. Two signaling pathways were used as models to validate our methods: beta-adrenergic agonistic activity on cAMP generation (dedicated dataset generated for this study) and EGFR ...[more]

PMID: 32541899

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Gene-signature-derived IC50s/EC50s reflect the potency of causative upstream targets and downstream phenotypes.

Publications

Gene-signature-derived IC<sub>50</sub>s/EC<sub>50</sub>s reflect the potency of causative upstream targets and downstream phenotypes.

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