MassIVE MSV000087954

Imported Reanalysis Dataset Public PXD018573

A mass spectrometry-based proteome map of drug action in lung cancer cell lines

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Description

Mass spectrometry-based discovery proteomics is an essential tool for the proximal read-out of cellular drug action. Here, we used a robust proteomic workflow to rapidly and systematically profile the proteomes of five cell lines in response to > 50 drugs. We found that aggregating millions of quantitative protein-drug associations substantially improved the mechanism of action (MoA) deconvolution of single compounds. For example, MoA specificity increased after removal of proteins which frequently responded to drugs and the aggregation of proteome changes across multiple cell lines resolved compound effects on proteostasis. These characteristics were further leveraged to demonstrate efficient target identification of protein degraders. Moreover, we followed up on selected proteomic findings and showed that the inhibition of mitochondrial function is an off-target mechanism of the clinical MEK inhibitor PD184352 and that Ceritinib, an FDA approved drug in lung cancer, modulates autophagy. Overall, this study demonstrates that large-scale proteome perturbation profiling can be a useful addition to the drug discovery toolbox. [doi:10.25345/C5RK1K] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Mass spectrometry ; Drug discovery ; Proteomics ; Perturbation profiling

Contact

Principal Investigators:
(in alphabetical order) 		An Chi, Merck, N/A
Submitting User: ccms

Publications

Ruprecht B, Di Bernardo J, Wang Z, Mo X, Ursu O, Christopher M, Fernandez RB, Zheng L, Dill BD, Wang H, Xu Y, Liaw A, Mortison JD, Siriwardana N, Andresen B, Glick M, Tata JR, Kutilek V, Cornella-Taracido I, Chi A.
A mass spectrometry-based proteome map of drug action in lung cancer cell lines.
Nat Chem Biol. 2020 Oct;16(10):1111-1119. Epub 2020 Jul 20.

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Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

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Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.