Schuffenhauer, A. | bioRxiv Science

bioRxiv2020

Systematic Chemogenetic Library Assembly

The assembly of chemogenetic libraries composed of chemical probes provides tremendous value to biomedical research, but requires substantial effort to ensure diversity as well as quality of the contents. We are assembling a chemogenetic library by data mining and crowdsourcing institutional expertise. We are sharing our methodology, lessons learned, and disclosing our current collection of 4186 compounds with their primary annotated gene targets.

bioinformatics↗

bioRxiv2019

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

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.

bioinformatics↗