Evidence map›Paper›PMID 35226415›Full record

ArticleMolecular systems biology2022

Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation.

Andreas-David Brunner, Marvin Thielert, Catherine Vasilopoulou, Constantin Ammar, Fabian Coscia, Andreas Mund, Ole B Hoerning, Nicolai Bache, Amalia Apalategui, Markus Lubeck and 7 more

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 301 papers.

0numbers the graph read from it
0cells of the map it votes in
301citing papers in PubMed
52.5field-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

301 citing papers in PubMed, 512 citations in OpenAlex.

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241 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 3 countries.

Andreas-David BrunnerProteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0002-2733-7899
Marvin ThielertProteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.
Catherine VasilopoulouProteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.
Constantin AmmarProteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0003-4310-6908
Fabian CosciaNNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-2244-5081
Andreas MundNNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-7843-5341
Ole B HoerningEvoSep Biosystems, Odense, Denmark.
Nicolai BacheEvoSep Biosystems, Odense, Denmark.
Amalia ApalateguiBruker Daltonik GmbH, Bremen, Germany.
Markus LubeckBruker Daltonik GmbH, Bremen, Germany.
Sabrina RichterHelmholtz Zentrum München - German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany.ORCID 0000-0001-6101-2783
David S FischerHelmholtz Zentrum München - German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany.ORCID 0000-0002-1293-7656
Oliver RaetherBruker Daltonik GmbH, Bremen, Germany.
Melvin A ParkBruker Daltonics Inc., Billerica, MA, USA.
Florian MeierProteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0003-4729-175X
Fabian J TheisHelmholtz Zentrum München - German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany.ORCID 0000-0002-2419-1943
Matthias MannProteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0003-1292-4799
Max Planck Institute of Biochemistry · DEBruker (Germany) · DEHelmholtz Zentrum München · DEUniversity of Copenhagen · DKBruker (United States) · USJena University Hospital · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Single-cell technologies are revolutionizing biology but are today mainly limited to imaging and deep sequencing. However, proteins are the main drivers of cellular function and in-depth characterization of individual cells by mass spectrometry (MS)-based proteomics would thus be highly valuable and complementary. Here, we develop a robust workflow combining miniaturized sample preparation, very low flow-rate chromatography, and a novel trapped ion mobility mass spectrometer, resulting in a more than 10-fold improved sensitivity. We precisely and robustly quantify proteomes and their changes in single, FACS-isolated cells. Arresting cells at defined stages of the cell cycle by drug treatment retrieves expected key regulators. Furthermore, it highlights potential novel ones and allows cell phase prediction. Comparing the variability in more than 430 single-cell proteomes to transcriptome data revealed a stable-core proteome despite perturbation, while the transcriptome appears stochastic. Our technology can readily be applied to ultra-high sensitivity analyses of tissue material, posttranslational modifications, and small molecule studies from small cell counts to gain unprecedented insights into cellular heterogeneity in health and disease.

Indexed as

ProteomeProteomicsMass SpectrometryProtein Processing, Post-TranslationalWorkflowProteomedrug perturbationlow-flow LC-MSproteomics at single-cell resolutionsingle-cell heterogeneitysystems biology

Identifiers

PMID35226415
PMCPMC8884154
OpenAlexW4214546240

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.