Evidence map›Paper›PMID 38354049›Full record

ArticleAnalytical chemistry2024

Targeted Quantification of Proteoforms in Complex Samples by Proteoform Reaction Monitoring.

Che-Fan Huang, Jake T Kline, Fernanda Negrão, Matthew T Robey, Timothy K Toby, Kenneth R Durbin, Ryan T Fellers, John J Friedewald, Josh Levitsky, Michael M I Abecassis and 3 more

Abstract read
In one paragraph

Article in Analytical chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Article
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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

13 authors.

Che-Fan HuangDepartments of Molecular Biosciences, Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States.
Jake T KlineSchool of Biological Sciences, University of Oklahoma, Norman, Oklahoma 73019, United States.
Fernanda NegrãoDepartments of Molecular Biosciences, Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States.
Matthew T RobeyDepartments of Molecular Biosciences, Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States.
Timothy K TobyDepartments of Molecular Biosciences, Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States.
Kenneth R DurbinDepartments of Molecular Biosciences, Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States.ORCID 0000-0001-7163-4877
Ryan T FellersDepartments of Molecular Biosciences, Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States.
John J FriedewaldComprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, United States.
Josh LevitskyComprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, United States.
Michael M I AbecassisComprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, United States.
Rafael D MelaniDepartments of Molecular Biosciences, Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States.
Neil L KelleherDepartments of Molecular Biosciences, Chemistry, and the Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States.ORCID 0000-0002-8815-3372
Luca FornelliSchool of Biological Sciences, University of Oklahoma, Norman, Oklahoma 73019, United States.ORCID 0000-0001-6334-1046

Funding

TR&D 7: Cell Specific ProteomicsP41GM108569 · NIGMS · NORTHWESTERN UNIVERSITY · PI KELLEHER, NEIL L · 2015 to 2024
$13.6M
A multi-level mass spectrometry pipeline for the analysis of whole proteoforms and their complexesR35GM147397 · NIGMS · UNIVERSITY OF OKLAHOMA · PI Luca Fornelli · 2022 to 2026
$1.9M
A comprehensive solution for native top down mass spectrometry data analyses across structural biology and biopharmaR44GM130262 · NIGMS · PROTEINACEOUS, INC. · PI DURBIN, KENNETH · 2022 to 2023
$1.6M
A proteoform-centric informatics platform for targeted top-down characterization and quantitationR43GM142386 · NIGMS · PROTEINACEOUS, INC. · PI DURBIN, KENNETH · 2021 to 2021
$252k
NIGMS NIH HHS P41 GM108569NIGMS NIH HHS R35 GM147397NIGMS NIH HHS R43 GM142386NIGMS NIH HHS R44 GM130262
6 · The paper itself

Abstract

Existing mass spectrometric assays used for sensitive and specific measurements of target proteins across multiple samples, such as selected/multiple reaction monitoring (SRM/MRM) or parallel reaction monitoring (PRM), are peptide-based methods for bottom-up proteomics. Here, we describe an approach based on the principle of PRM for the measurement of intact proteoforms by targeted top-down proteomics, termed proteoform reaction monitoring (PfRM). We explore the ability of our method to circumvent traditional limitations of top-down proteomics, such as sensitivity and reproducibility. We also introduce a new software program, Proteoform Finder (part of ProSight Native), specifically designed for the easy analysis of PfRM data. PfRM was initially benchmarked by quantifying three standard proteins. The linearity of the assay was shown over almost 3 orders of magnitude in the femtomole range, with limits of detection and quantification in the low femtomolar range. We later applied our multiplexed PfRM assay to complex samples to quantify biomarker candidates in peripheral blood mononuclear cells (PBMCs) from liver-transplanted patients, suggesting their possible translational applications. These results demonstrate that PfRM has the potential to contribute to the accurate quantification of protein biomarkers for diagnostic purposes and to improve our understanding of disease etiology at the proteoform level.

Indexed as

Leukocytes, MononuclearProteinsHumansMass SpectrometryProtein Processing, Post-TranslationalProteomeProteomicsReproducibility of ResultsProteinsProteome

Identifiers

PMID38354049
PMCPMC11008684

What OpenQuestion holds

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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.