Modanovo: A Unified Model for Post-translational Modification-Aware De Novo Sequencing Using Experimental Spectra From In Vivo and Synthetic Peptides.

ABSTRACT: Post-translational modifications (PTMs) play a central role in cellular regulation and are implicated in numerous diseases. Database searching remains the standard for identifying modified peptides from tandem mass spectra but is hindered by the combinatorial expansion of modification types and sites. De novo peptide sequencing offers an attractive alternative, yet existing methods remain limited to unmodified peptides or a narrow set of PTMs. Here, we curated a large dataset of spectra from endogenous and synthetic peptides from ProteomeTools spanning 19 biologically relevant amino acid-PTM combinations, covering phosphorylation, acetylation, and ubiquitination. We used this dataset to develop Modanovo, an extension of the Casanovo transformer architecture for de novo peptide sequencing.

SUBMITTER: Klaproth-Andrade D 

PROVIDER: S-EPMC12860953 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature