Cell Painting and Thermal Proteome Profiling for Inference of Drug Targets and Mechanism of Action

ABSTRACT: Understanding the mechanism of action (MoA) of bioactive compounds is a central challenge in drug discovery and chemical biology. We propose a strategy for integrating morphological data with proteomics to provide deeper insights into the MoA of compounds. We combine the rich phenotypic profiles of Cell Painting (CP) with the unbiased protein target detection of Thermal Proteome Profiling (TPP), and construct protein--protein interaction networks based on potential targets identified using both assays. We validated our method with public TPP data sets for the five compounds (+)-JQ1, I-BET151, Vemurafenib, Crizotinib and Panobinostat, and public Proteome Integral Solubility Alteration (PISA) data for 49 compounds, together with CP data for 5259 drugs on U2OS cells. We show that the combined

SUBMITTER: Camilla Johansson 

PROVIDER: S-SCDT-10_1038-S44320-026-00214-9 | biostudies-other |

REPOSITORIES: biostudies-other