Evidence map›Paper›PMID 33290830›Full record

ArticleToxicology letters2021

A direct peptide reactivity assay using a high-throughput mass spectrometry screening platform for detection of skin sensitizers.

Zhengxi Wei, Yuhong Fang, Maya L Gosztyla, Andrew J Li, Wenwei Huang, Christopher A LeClair, Anton Simeonov, Dingyin Tao, Menghang Xia

Open access · hybridAbstract read
In one paragraph

Article in Toxicology letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 19% 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

4 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Use ofFrontiers in toxicology · 2024
    Article
  4. Article
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

9 authors at 2 institutions in 1 country.

Zhengxi WeiDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States.
Yuhong FangDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States.
Maya L GosztylaDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States.
Andrew J LiDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States.
Wenwei HuangDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States.
Christopher A LeClairDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States.
Anton SimeonovDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States.
Dingyin TaoDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States. Electronic address: dingyin.tao@nih.gov.
Menghang XiaDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, United States. Electronic address: xia@mail.nih.gov.
National Center for Advancing Translational Sciences · USNational Institutes of Health · US

Funding

Analytical ChemistryZICTR000037 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI LECLAIR, CHRISTOPHER ARTHUR · 2015 to 2025
$23.2M
Toxicology in the 21st Century Program (Tox21) - Systems ToxicologyZIATR000038 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI XIA, MENGHANG · 2015 to 2025
$5.7M
Intramural NIH HHS Z99 TR999999
6 · The paper itself

Abstract

Chemical-peptide conjugation is the molecular initiating event in skin sensitization. The OECD test guideline uses a high-performance liquid chromatography/ultraviolet (HPLC/UV) detection method to quantify chemical-peptide conjugation in a direct peptide reactivity assay (DPRA), which measures the depletion of two synthetic peptides containing lysine or cysteine residues. To improve assay throughput, sensitivity and accuracy, an automated 384-well plate-based RapidFire solid-phase extraction (SPE) system coupled with tandem mass spectrometry (MS/MS) DPRA was developed and validated in the presence of a newly designed internal standard. Compared to the HPLC/UV-based DPRA, the automated SPE-MS/MS-based DPRA improved throughput from 16 min to 10 s per sample, and substrate peptides usage was reduced from 100 mM to 5 μM. When implementing the SPE-MS/MS-based DPRA into a high-throughput platform, we found 10 compounds that depleted lysine peptide and 24 compounds that depleted cysteine peptide (including 7 unreported chemicals from 55 compounds we tested) in a concentration-response manner. The adduct formation between cysteine and cinnamic aldehyde and ethylene glycol dimethacrylate were further analyzed using high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF-MS) to confirm the conjugation. Overall, the automated SPE-MS/MS-based platform is an efficient, economic, and accurate way to detect skin sensitizers.

Indexed as

Chromatography, High Pressure LiquidHigh-Throughput Screening AssaysTandem Mass SpectrometryToxicity TestsAllergensAnimal Testing AlternativesCysteineDermatitis, Allergic ContactHumansLysinePeptidesReference StandardsReproducibility of ResultsRisk AssessmentSkinAllergensCysteineLysinePeptidesDirect peptide reaction assay (DPRA)High throughput mass spectrometryRapidFire-MS/MS

Identifiers

PMID33290830
PMCPMC9527016
OpenAlexW3113208072

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.