Evidence map›Paper›PMID 38118439›Full record

ArticleCell chemical biology2024

Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input.

Ka Yang, Rebecca L Whitehouse, Shane L Dawson, Lu Zhang, Jeffrey G Martin, Douglas S Johnson, Joao A Paulo, Steven P Gygi, Qing Yu

Abstract read
In one paragraph

Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
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

27 citing papers in PubMed.

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  17. Article
  18. Covalent Proximity Inducers.Chemical reviews · 2025
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Ka YangDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Rebecca L WhitehouseDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Shane L DawsonDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Lu ZhangBiogen, Cambridge, MA 02142, USA.
Jeffrey G MartinBiogen, Cambridge, MA 02142, USA.
Douglas S JohnsonBiogen, Cambridge, MA 02142, USA.
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: steven_gygi@hms.harvard.edu.
Qing YuDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: qing_yu2@hms.harvard.edu.

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
Advancing Multiplexed Isobaric Tag-based Strategies for Proteome ProfilingR01GM132129 · NIGMS · HARVARD MEDICAL SCHOOL · PI PAULO, JOAO A · 2019 to 2023
$1.7M
NIGMS NIH HHS R01 GM067945NIGMS NIH HHS R01 GM132129
6 · The paper itself

Abstract

Chemoproteomics has made significant progress in investigating small-molecule-protein interactions. However, the proteome-wide profiling of cysteine ligandability remains challenging to adapt for high-throughput applications, primarily due to a lack of platforms capable of achieving the desired depth using low input in 96- or 384-well plates. Here, we introduce a revamped, plate-based platform which enables routine interrogation of either ∼18,000 or ∼24,000 reactive cysteines based on starting amounts of 10 or 20 μg, respectively. This represents a 5-10X reduction in input and 2-3X improved coverage. We applied the platform to screen 192 electrophiles in the native HEK293T proteome, mapping the ligandability of 38,450 reactive cysteines from 8,274 human proteins. We further applied the platform to characterize new cellular targets of established drugs, uncovering that ARS-1620, a KRAS

Indexed as

CysteineProteomeHEK293 CellsHumansLigandsCysteineLigandsProteomeABPPchemoproteomicscovalent electrophilecysteinehigh throughputTMT

Identifiers

PMID38118439
PMCPMC10960705

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Registered trials

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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.