Evidence map›Paper›PMID 33188197›Full record

ArticleNature communications2020

A computational method for detection of ligand-binding proteins from dose range thermal proteome profiles.

Nils Kurzawa, Isabelle Becher, Sindhuja Sridharan, Holger Franken, André Mateus, Simon Anders, Marcus Bantscheff, Wolfgang Huber, Mikhail M Savitski

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. 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 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 53 citations in OpenAlex.

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  11. Stability-based approaches in chemoproteomics.Expert reviews in molecular medicine · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Nils Kurzawa *European Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, 69117, Germany.ORCID http://orcid.org/0000-0002-7846-2817
Isabelle Becher *European Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, 69117, Germany.ORCID http://orcid.org/0000-0001-7170-2235
Sindhuja SridharanEuropean Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, 69117, Germany.ORCID http://orcid.org/0000-0003-4548-2624
Holger FrankenCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, 69117, Germany.
André MateusEuropean Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, 69117, Germany.ORCID http://orcid.org/0000-0001-6870-0677
Simon AndersCenter for Molecular Biology of Heidelberg University (ZMBH), Im Neuenheimer Feld 282, Heidelberg, 69120, Germany.ORCID http://orcid.org/0000-0003-4868-1805
Marcus BantscheffCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, 69117, Germany. marcus.x.bantscheff@gsk.com.ORCID http://orcid.org/0000-0002-8343-8977
Wolfgang HuberEuropean Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, 69117, Germany. wolfgang.huber@embl.org.ORCID http://orcid.org/0000-0002-0474-2218
Mikhail M SavitskiEuropean Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, 69117, Germany. mikhail.savitski@embl.de.ORCID http://orcid.org/0000-0003-2011-9247
European Molecular Biology Laboratory · DEEuropean Molecular Biology Laboratory · ESGlaxoSmithKline (Germany) · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Detecting ligand-protein interactions in living cells is a fundamental challenge in molecular biology and drug research. Proteome-wide profiling of thermal stability as a function of ligand concentration promises to tackle this challenge. However, current data analysis strategies use preset thresholds that can lead to suboptimal sensitivity/specificity tradeoffs and limited comparability across datasets. Here, we present a method based on statistical hypothesis testing on curves, which provides control of the false discovery rate. We apply it to several datasets probing epigenetic drugs and a metabolite. This leads us to detect off-target drug engagement, including the finding that the HDAC8 inhibitor PCI-34051 and its analog BRD-3811 bind to and inhibit leucine aminopeptidase 3. An implementation is available as an R package from Bioconductor ( https://bioconductor.org/packages/TPP2D ). We hope that our method will facilitate prioritizing targets from thermal profiling experiments.

Indexed as

ProteomicsTemperatureAdenosine TriphosphateComputational BiologyDatabases, ProteinGuanosine TriphosphateHep G2 CellsHistone Deacetylase InhibitorsHistone DeacetylasesHumansHydroxamic AcidsIndolesLeucyl AminopeptidaseLigandsPharmaceutical PreparationsProtein BindingAdenosine TriphosphateGuanosine TriphosphateHDAC8 protein, humanHistone Deacetylase InhibitorsHistone DeacetylasesHydroxamic AcidsIndolesLAP3 protein, humanLeucyl AminopeptidaseLigandsPCI 34051Pharmaceutical PreparationsProteomeRepressor Proteins

Identifiers

PMID33188197
PMCPMC7666118
OpenAlexW3099234957

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.