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Integrating Cell Painting and Thermal Proteome Profiling for Inference of 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. In this article, 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 evaluate our method on public TPP data sets for the five compounds (+)-JQ1, I-BET151, Vemurafenib, Crizotinib and Panobinostat, together with Cell Painting data for 5270 drugs on U2OS cells. We show that the combined approach could accurately identify known MoAs for four out of five compounds. This work highlights the value of multimodal profiling for chemical biology and opens new avenues for data-driven discovery of therapeutic mechanisms.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bone Cancer Cell Line, Bone Cell

SUBMITTER: Mårten Larsson

LAB HEAD: Erik T. Jansson

PROVIDER: PXD065743 | Pride | 2025-12-18

REPOSITORIES: Pride

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			Action	DRS
	2024-11-22-decoys-Human_UP000005640_SwissProt_241121_con.fasta.fas	Fasta
	250609_Phani_TMT_1.raw	Raw
	250609_Phani_TMT_2.raw	Raw
	250609_Phani_TMT_3.raw	Raw
	250609_Phani_TMT_4.raw	Raw

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