Evidence map›Paper›PMID 41038282›Full record

ArticleMolecular & cellular proteomics : MCP2025

Breaking Boundaries in Histone Modification MS-Based Detection: A Tailored Search Strategy for Unrestricted Identification of Novel Epigenetic Marks.

Alessandro Vai, Roberta Noberini, Andrea Graziadei, Daniel A Polasky, Fengchao Yu, Alexey I Nesvizhskii, Tiziana Bonaldi

Abstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

7 authors.

Alessandro VaiDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCSS, Milan, Italy.
Roberta NoberiniDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCSS, Milan, Italy.
Andrea GraziadeiHuman Technopole, Milan, Italy.
Daniel A PolaskyDepartment of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Fengchao YuDepartment of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Alexey I NesvizhskiiDepartment of Pathology, University of Michigan, Ann Arbor, Michigan, USA; Gilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: nesvi@med.umich.edu.
Tiziana BonaldiDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCSS, Milan, Italy; Department of Oncology and Hematology-Oncology, University of Milan, Milan, Italy. Electronic address: tiziana.bonaldi@ieo.it.

Funding

COMPUTATIONAL TOOLS FOR MASS SPECTROMETRY-BASED INTERACTOME DATAR01GM094231 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 2010 to 2026
$5.4M
Michigan Center for Translational Cancer Proteogenomics-Diversity SupplementU24CA271037 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Saravana Mohan Dhanasekaran, Alexey I Nesvizhskii · 2022 to 2026
$4.4M
NCI NIH HHS U24 CA271037NIGMS NIH HHS R01 GM094231
6 · The paper itself

Abstract

Histone post-translational modifications (PTMs) play a crucial role in regulating gene expression and maintaining DNA integrity, and their aberrations are linked to various diseases, including cancer. While lysine acetylation and methylation have been extensively studied, recent research has uncovered additional PTMs that significantly contribute to chromatin structure and function. Mass spectrometry is the most effective analytical method for studying histone PTMs; however, computational limitations often restrict the analysis to common modifications. Unrestrictive search strategies have the potential to enable a more comprehensive characterization of the histone modification landscape. In this work, we systematically assess the application of unrestrictive search approaches to histone data. After evaluating the limitations of these methods, we develop a novel bioinformatics workflow, named HiP-Frag (histone PTM analysis with FragPipe), which enables the identification of 96 sites decorated with uncommon PTMs on core histones-60 of which were previously unreported-as well as 55 histone marks on linker histones, including 13 novel ones, purified from human cell lines and primary samples. The expanded histone PTM analysis enabled by this strategy is among the first to extract previously unexplored epigenetic information from mass spectrometry raw data. This approach paves the way for a facilitated and more streamlined identification of uncommon and yet unannotated histone modifications, supporting a deeper dissection of the histone code and the understanding of the potential biological role of the novel epigenetic marks.

Indexed as

Computational BiologyEpigenesis, GeneticHistone CodeHistonesHumansMass SpectrometryProtein Processing, Post-TranslationalHistonesbioinformatics workflowepigeneticshistone PTM discoverymass spectrometrypost-translational modifications

Identifiers

PMID41038282
PMCPMC12634847

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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.