PXD076296-1

PXD076296 is an original dataset announced via ProteomeXchange.

Title	Zero-Shot De Novo Peptide Sequencing with Open Post-Translational Modification Discovery
Description	Proteins play essential roles in biology, yet identifying their precise sequences and modifications remains challenging. De novo peptide sequencing offers a powerful solution by directly inferring sequences from mass spectrometry data without relying on protein databases. Recent deep learning models have significantly advanced this task but remain trapped in a major dilemma: they require labeled training data to recognize post-translational modifications (PTMs), which is unavailable for most biologically relevant but rare or unknown modifications. We solve this long-standing problem by introducing RNovA, a transformer-based de novo sequencing algorithm enhanced with relative positional embeddings and a reinforcement-learning–style sequential decision framework. RNovA enables open PTM discovery in a zero-shot settingwithout retraining or a predefined list of candidate residues—while maintaining state-of-the-art performance on standard benchmarks. Demonstrating this capability, we successfully identified peptides modified by kynurenine—an uncommon and biologically relevant PTM—in clinical samples from rheumatoid arthritis patients. RNovA overcomes key limitations of existing methods and provides a foundation for exploring previously inaccessible regions of the proteome, including peptides with unexpected or unannotated modifications. This capability is widely needed in immunology, biomarker discovery, and biomedical research.
HostingRepository	PRIDE
AnnounceDate	2026-03-29
AnnouncementXML	Submission_2026-03-29_09:56:06.564.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zeping Mao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: NEWT:4932;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; orbitrap; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-29 09:04:07	ID requested
⏵ 1	2026-03-29 09:56:07	announced

Dataset with its publication pending

submitter keyword: De Novo, Deep Learning,PTM

Ming Li
contact affiliation	Canada Research Chair in Bioinformatics University Professor David R. Cheriton School of Computer Science University of Waterloo, Ontario, Canada
contact email	mli@uwaterloo.ca
lab head
Zeping Mao
contact affiliation	University of Waterloo
contact email	z37mao@uwaterloo.ca
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/2026/03/PXD076296

PRIDE project URI

• PRIDE
  1. PXD076296
     1. Label: PRIDE project
     2. Name: Zero-Shot De Novo Peptide Sequencing with Open Post-Translational Modification Discovery