Autor: |
Pierre Farmer, Ansgar Schuffenhauer, Nicole Reymann, Magdalena Koziczak-Holbro, Sebastian Hoersch, Edward James Oakeley, Rochdi Bouhelal, Eugen Lounkine, Hanspeter Gubler, Karen Kapur, Ludivine Flotte, Steffen Renner, Christian Bergsdorf, Andrea Marco Amati, Valerie Techer-Etienne |
Rok vydání: |
2019 |
Předmět: |
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DOI: |
10.1101/799106 |
Popis: |
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 EC50and IC50values.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.Our results show that gene-signature potencies are a novel valid alternative to conventional readouts for compound potency quantification, in particular in scenarios where no other established readouts are available. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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