Gene-signatures predict biologically relevant dose-response potencies in phenotypic assays
Renner, S.; Bergsdorf, C.; Bouhelal, R.; Koziczak-Holbro, M.; Amati, A. M.; Techer-Etienne, V.; Flotte, L.; Reymann, N.; Kapur, K.; Hoersch, S.; Oakeley, E. J.; Schuffenhauer, A.; Gubler, H.; Lounkine, E.; Farmer, P.
Show 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.\n\nTwo 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.\n\nOur 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.
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