Evidence map›Paper›PMID 36526727›Full record

ReviewNature protocols2023

Proteome-wide structural changes measured with limited proteolysis-mass spectrometry: an advanced protocol for high-throughput applications.

Liliana Malinovska, Valentina Cappelletti, Devon Kohler, Ilaria Piazza, Tsung-Heng Tsai, Monika Pepelnjak, Patrick Stalder, Christian Dörig, Fabian Sesterhenn, Franziska Elsässer and 6 more

Erratum issuedAbstract readReview
PubMed Publisher
In one paragraph

Review in Nature protocols, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
10.5field-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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.

  1. Pooled it
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  7. Review
  8. Proteomics-Driven Strategies for Proximity-Inducing Drug Discovery.Angewandte Chemie (International ed. in English) · 2026
    Review
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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 3 countries.

Liliana Malinovska *Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-8514-4569
Valentina Cappelletti *Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Devon Kohler *Khoury College of Computer Sciences, Northeastern University, Boston, MA, USA.
Ilaria PiazzaMax Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC Berlin), Berlin, Germany.ORCID http://orcid.org/0000-0001-5895-6134
Tsung-Heng TsaiDepartment of Mathematical Sciences, Kent State University, Kent, OH, USA.ORCID http://orcid.org/0000-0001-5211-2985
Monika PepelnjakInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Patrick StalderInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Christian DörigInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-4213-8855
Fabian SesterhennInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Franziska ElsässerInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Lucie KralickovaInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Nigel BeatonBiognosys AG, Schlieren, Switzerland.
Lukas ReiterBiognosys AG, Schlieren, Switzerland.ORCID http://orcid.org/0000-0001-5751-3139
Natalie de SouzaInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Olga VitekKhoury College of Computer Sciences, Northeastern University, Boston, MA, USA. o.vitek@northeastern.edu.
Paola PicottiInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland. picotti@imsb.biol.ethz.ch.
ETH Zurich · CHBiognosys (Switzerland) · CHNortheastern University · USKent State University · USMax Delbrück Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteins regulate biological processes by changing their structure or abundance to accomplish a specific function. In response to a perturbation, protein structure may be altered by various molecular events, such as post-translational modifications, protein-protein interactions, aggregation, allostery or binding to other molecules. The ability to probe these structural changes in thousands of proteins simultaneously in cells or tissues can provide valuable information about the functional state of biological processes and pathways. Here, we present an updated protocol for LiP-MS, a proteomics technique combining limited proteolysis with mass spectrometry, to detect protein structural alterations in complex backgrounds and on a proteome-wide scale. In LiP-MS, proteins undergo a brief proteolysis in native conditions followed by complete digestion in denaturing conditions, to generate structurally informative proteolytic fragments that are analyzed by mass spectrometry. We describe advances in the throughput and robustness of the LiP-MS workflow and implementation of data-independent acquisition-based mass spectrometry, which together achieve high reproducibility and sensitivity, even on large sample sizes. We introduce MSstatsLiP, an R package dedicated to the analysis of LiP-MS data for the identification of structurally altered peptides and differentially abundant proteins. The experimental procedures take 3 d, mass spectrometric measurement time and data processing depend on sample number and statistical analysis typically requires ~1 d. These improvements expand the adaptability of LiP-MS and enable wide use in functional proteomics and translational applications.

Indexed as

Protein Processing, Post-TranslationalProteomeMass SpectrometryProteolysisReproducibility of ResultsProteome

Identifiers

PMID36526727
OpenAlexW4311685631

What OpenQuestion holds

Textmetadata
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.