Dataset Information

TargetSeeker-MS: A Bayesian Inference Approach for Drug Target Discovery using Protein Fractionation Coupled to Mass Spectrometry

ABSTRACT: Determining the affinity of a drug to its putative targets is critical to the understanding of its mechanism and to assess its clinical usefulness and viability. Energetics-based protein separation (EBPS) techniques, such as thermal shift assay, when coupled to mass spectrometry (MS) have shown great potential to identify the targets of a drug on a proteome scale. Nevertheless, the computational analyses assessing the confidence of drug target predictions made by these methods have remained rudimentary and tightly tied to the protocol under which the data were produced. We propose a novel flexible Bayesian inference approach named TargetSeeker-MS to identify drug targets in datasets produced using different EBPS techniques coupled to MS. We show that TargetSeeker-MS identifies known and novel drug targets in C. elegans and HEK 293 samples treated with benomyl, a fungicide. We also demonstrate that TargetSeeker-MS’ drug target identifications are reproducible in C. elegans samples that were processed using two different EBPS techniques (thermal shift assay and a selective precipitation-based separation). In addition, we validate a novel benomyl target by measuring its altered enzymatic activity upon drug treatment in vitro. TargetSeeker-MS, which is available as a web server, allows for the rapid and confident identification of targets of a drug on a proteome scale, thereby providing a better understanding of its mechanisms to ease the evaluation of its clinical viability.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Caenorhabditis Elegans

TISSUE(S): Cell Culture, Whole Body

SUBMITTER: James Moresco

LAB HEAD: John R. Yates III

PROVIDER: PXD010799 | Pride | 2026-04-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20150711_FF_10ul_CB1.raw	Raw
	20150711_FF_10ul_CB1.sqt	Other
	20150711_FF_10ul_CB10.raw	Raw
	20150711_FF_10ul_CB10.sqt	Other
	20150711_FF_10ul_CB2.raw	Raw

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Publications

TargetSeeker-MS: A Bayesian Inference Approach for Drug-Target Discovery Using Protein Fractionation Coupled to Mass Spectrometry.

Lavallée-Adam Mathieu M Pelletier Alexander A Diedrich Jolene K JK Pinto Antonio F M AFM Martínez-Bartolomé Salvador S Petrascheck Michael M Moresco James J JJ Yates John R JR

Journal of the American Society for Mass Spectrometry 20250311 4

To understand the mechanism of action of a drug and assess its clinical usefulness and viability, it is imperative that its affinity for its putative targets is determined. When coupled to mass spectrometry (MS), energetics-based protein separation (EBPS) techniques, such as a thermal shift assay, have shown great potential to identify the targets of a drug on a proteome scale. Nevertheless, the computational analyses assessing the confidence of drug-target predictions made by these methods have ...[more]

PMID: 40067882

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