PXD061934-1

PXD061934 is an original dataset announced via ProteomeXchange.

Title	Breaking Boundaries in Histone Modification MS-based Detection: A Tailored Search Strategy for Unrestricted identification of novel epigenetic marks
Description	Histone post-translational modifications (PTMs) are crucial for gene expression regulation and DNA maintenance, and their aberrations are linked to multiple diseases, like cancer. While functions related to lysine acetylation and methylation have been well-studied, recent studies have uncovered additional PTMs that also contribute significantly to chromatin structure and function. Mass Spectrometry (MS) is the most effective analytical method for studying histone PTMs, but computational limitations often restrict the analysis to common modifications. Unrestrictive search strategies hold the potential for an in-depth characterization of the histone modifications landscape. In this work, we carry out a systematic assessment of the application of unrestrictive search approaches to histone data. We assess the limitations of these approaches, and we implement and test an optimized bioinformatics workflow, HiP-Frag (Histone PTMs analysis with FragPipe), which allows the identification of 201 sites modified by uncommon modifications (127 of these were previously unreported) on core histones and 82 modified sites on the linker histones purified form human cell lines and primary samples, greatly contributing to the expansion of the catalogue of histone modifications. The comprehensive analysis of histone PTMs enabled by this strategy is one of the first to leverage previously unexplored epigenetic information in MS raw data. This approach opens the door to identifying uncommon, difficult-to-detect, and yet unannotated histone modifications, leading to a more complete annotation of the histone code and a potential deeper understanding of the roles of novel, less-characterized histone marks in both physiological and disease conditions.
HostingRepository	PRIDE
AnnounceDate	2025-11-11
AnnouncementXML	Submission_2025-11-11_06:02:50.865.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alessandro Vai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monomethylated residue; N6-(2-hydroxyisobutanoyl)-L-lysine; N6-malonyl-L-lysine; phosphorylated residue; N6-crotonyl-L-lysine; N6; acetylated residue; formylated residue; N6
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-17 11:07:37	ID requested
⏵ 1	2025-11-11 06:02:51	announced

10.1016/j.mcpro.2025.101080;

Vai A, Noberini R, Graziadei A, Polasky DA, Yu F, Nesvizhskii AI, Bonaldi T, Breaking Boundaries in Histone Modification MS-Based Detection: A Tailored Search Strategy for Unrestricted Identification of Novel Epigenetic Marks. Mol Cell Proteomics, 24(11):101080(2025) [pubmed]

submitter keyword: Human, LC-MSMS, Bioinformatics, Epigenetics, Histone Post-Translational Modifications, Open Search

Tiziana Bonaldii
contact affiliation	Department of Experimental Oncology, IEO, European Institute of Oncology IRCSS, 20139, Milan, Italy
contact email	tiziana.bonaldi@ieo.it
lab head
Alessandro Vai
contact affiliation	European Institute of Oncology (IEO)
contact email	alessandro.vai@ieo.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD061934

PRIDE project URI

• PRIDE
  1. PXD061934
     1. Label: PRIDE project
     2. Name: Breaking Boundaries in Histone Modification MS-based Detection: A Tailored Search Strategy for Unrestricted identification of novel epigenetic marks