PepPr: De Novo peptide sequencing with peptide priors

PepPr, a de novo peptide sequencing method using a peptide prior from a reference proteome, improved reference peptide identification and variant identification versus prior-free DNPS.

• Why it matters: DNPS often fails with incomplete spectra, and prior hybrid approaches either correct after database search or reuse previously identified spectra, limiting robust discovery.
• What they did: PepPr combines DNPS with a language model fitted to a reference proteome, tolerating variants while remaining uncertain on strongly divergent sequences.
• The result: With a related proteome as prior, PepPr matched or outperformed homology-driven database search, and in antibody sequencing it improved recovery across the variable–constant boundary, deamidation calls, and assembly.