Evidence map›Paper›PMID 33398154›Full record

ArticleNature biotechnology2021

Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries.

Miljan Kuljanin, Dylan C Mitchell, Devin K Schweppe, Ajami S Gikandi, David P Nusinow, Nathan J Bulloch, Ekaterina V Vinogradova, David L Wilson, Eric T Kool, Joseph D Mancias and 2 more

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed
26.4field-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

160 citing papers in PubMed, 319 citations in OpenAlex.

  1. Review
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  6. Proteomics-Driven Strategies for Proximity-Inducing Drug Discovery.Angewandte Chemie (International ed. in English) · 2026
    Review
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100 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

12 authors at 3 institutions in 1 country.

Miljan KuljaninDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Dylan C MitchellDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Devin K SchweppeDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3241-6276
Ajami S GikandiDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
David P NusinowDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7819-5261
Nathan J BullochDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Ekaterina V VinogradovaDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
David L WilsonDepartment of Chemistry, Stanford Cancer Institute and ChEM-H Institute, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1922-427X
Eric T KoolDepartment of Chemistry, Stanford Cancer Institute and ChEM-H Institute, Stanford University, Stanford, CA, USA.
Joseph D ManciasDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Benjamin F CravattDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA. steven_gygi@hms.harvard.edu.ORCID http://orcid.org/0000-0001-7626-0034
Harvard University · USScripps Research Institute · USStanford University · US

Funding

New Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5M
Chemical Proteomic Platforms for Radically Expanding Cancer DruggabilityR35CA231991 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI BENJAMIN F CRAVATT · 2018 to 2026
$9.5M
Measuring and Modulating Oxidative DNA Damage Surveillance PathwaysR01CA217809 · NCI · STANFORD UNIVERSITY · PI KOOL, ERIC T. · 2017 to 2024
$3.7M
NCI NIH HHS R01 CA217809NCI NIH HHS R35 CA231991NIGMS NIH HHS R01 GM067945
6 · The paper itself

Abstract

Current methods used for measuring amino acid side-chain reactivity lack the throughput needed to screen large chemical libraries for interactions across the proteome. Here we redesigned the workflow for activity-based protein profiling of reactive cysteine residues by using a smaller desthiobiotin-based probe, sample multiplexing, reduced protein starting amounts and software to boost data acquisition in real time on the mass spectrometer. Our method, streamlined cysteine activity-based protein profiling (SLC-ABPP), achieved a 42-fold improvement in sample throughput, corresponding to profiling library members at a depth of >8,000 reactive cysteine sites at 18 min per compound. We applied it to identify proteome-wide targets of covalent inhibitors to mutant Kirsten rat sarcoma (KRAS)

Indexed as

Agammaglobulinaemia Tyrosine KinaseAmino AcidsAntioxidant Response ElementsCysteineHumansMass SpectrometryProteomeProteomicsProto-Oncogene Proteins p21(ras)Agammaglobulinaemia Tyrosine KinaseAmino AcidsCysteineKRAS protein, humanProteomeProto-Oncogene Proteins p21(ras)

Identifiers

PMID33398154
PMCPMC8316984
OpenAlexW3120879514

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.