Gene-signatures predict biologically relevant dose-response potencies in phenotypic assays

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:
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