Evidence map›Paper›PMID 36926954›Full record

ArticleScience (New York, N.Y.)2023

Decrypting drug actions and protein modifications by dose- and time-resolved proteomics.

Jana Zecha, Florian P Bayer, Svenja Wiechmann, Julia Woortman, Nicola Berner, Julian Müller, Annika Schneider, Karl Kramer, Mar Abril-Gil, Thomas Hopf and 27 more

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
15.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 100 citations in OpenAlex.

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  15. Variable thresholds for phosphorylation targets of the ERK signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors at 4 institutions in 1 country.

Jana Zecha *Proteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-8767-6294
Florian P Bayer *Proteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0001-6489-2835
Svenja Wiechmann *Proteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0003-1324-0743
Julia WoortmanProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0003-4189-3434
Nicola BernerProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.
Julian MüllerProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0003-4108-7926
Annika SchneiderProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-7684-7801
Karl KramerProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0003-2180-5652
Mar Abril-GilInstitute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.ORCID 0000-0003-0318-6755
Thomas HopfOmicScouts GmbH, 85354 Freising, Germany.ORCID 0000-0002-7476-9539
Leonie ReichartOmicScouts GmbH, 85354 Freising, Germany.
Lin ChenProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-3601-299X
Fynn M HansenProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-0370-8173
Severin LechnerProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0003-2297-9208
Patroklos SamarasProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0001-6042-1585
Stephan EckertProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-6959-4439
Ludwig LautenbacherProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-1540-5911
Maria ReineckeProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.
Firas HamoodProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-4141-7051
Polina ProkofevaProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0001-9528-2204
Larsen VornholzInstitute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.ORCID 0000-0002-8054-5603
Chiara FalcomatàGerman Cancer Consortium, Partner Site Munich, 80336 Munich, Germany.ORCID 0000-0001-9269-2582
Madeleine DorschDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, 45147 Essen, Germany.ORCID 0000-0002-5998-4177
Ayla SchröderOmicScouts GmbH, 85354 Freising, Germany.ORCID 0000-0002-1424-3666
Anton VenhuizenProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-7314-1467
Stephanie WilhelmProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-1066-6565
Guillaume MédardProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-4782-4029
Gabriele StoehrOmicScouts GmbH, 85354 Freising, Germany.
Jürgen RulandGerman Cancer Consortium, Partner Site Munich, 80336 Munich, Germany.ORCID 0000-0002-8381-3597
Barbara M GrünerDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, 45147 Essen, Germany.ORCID 0000-0003-0974-4826
Dieter SaurGerman Cancer Consortium, Partner Site Munich, 80336 Munich, Germany.ORCID 0000-0001-5874-0210
Maike BuchnerInstitute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
Benjamin RuprechtProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.
Hannes HahneOmicScouts GmbH, 85354 Freising, Germany.ORCID 0000-0003-3601-0051
Matthew TheProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-5401-5553
Mathias WilhelmProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-9224-3258
Bernhard KusterProteomics and Bioanalytics, Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.ORCID 0000-0002-9094-1677
Technical University of Munich · DETUM Klinikum · DEDeutschen Konsortium für Translationale Krebsforschung · DEEssen University Hospital · DE

Funding

European Research Council 833710
6 · The paper itself

Abstract

Although most cancer drugs modulate the activities of cellular pathways by changing posttranslational modifications (PTMs), little is known regarding the extent and the time- and dose-response characteristics of drug-regulated PTMs. In this work, we introduce a proteomic assay called decryptM that quantifies drug-PTM modulation for thousands of PTMs in cells to shed light on target engagement and drug mechanism of action. Examples range from detecting DNA damage by chemotherapeutics, to identifying drug-specific PTM signatures of kinase inhibitors, to demonstrating that rituximab kills CD20-positive B cells by overactivating B cell receptor signaling. DecryptM profiling of 31 cancer drugs in 13 cell lines demonstrates the broad applicability of the approach. The resulting 1.8 million dose-response curves are provided as an interactive molecular resource in ProteomicsDB.

Indexed as

Antineoplastic AgentsApoptosisProtein Processing, Post-TranslationalProteomicsAntigens, CD20B-LymphocytesCell Line, TumorDNA DamageHumansReceptors, Antigen, B-CellSignal TransductionAntigens, CD20Antineoplastic AgentsReceptors, Antigen, B-Cell

Identifiers

PMID36926954
PMCPMC7615311
OpenAlexW4327549849

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.