Deep coverage and extended sequence reads obtained with a single archaeal protease expedite de novo protein sequencing by mass spectrometry

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On 2026-04-092026-04-09By In Featured User Publications

Advancing de novo Antibody Sequencing with Hyperthermal Proteases and Next‑Gen Fragmentation

A recent Cell Systems study coming from our collaborators at CinderBio, led by Dr. Steven Yannone, in a joint work with Dr. Albert Heck's lab, highlights how highly efficient hyperthermal acidic proteases, combined with hybrid-fragmentation schemes, greatly boost confidence in de novo sequencing. Combining the HTA-based hyperthermal single-protease approach with powerful ZenoTOF EAciD fragmentation provides information-rich spectra and enables confident de novo antibody sequencing based on a single LC-MS run.

Conventional tryptic digestion often produces short peptides and limited coverage of complementarity‑determining regions (CDRs). As a result, de novo antibody sequencing typically requires multiple proteases and repeated MS analyses, increasing complexity and cost. In this study, hyperthermoacidic archaeal proteases were used to generate long, overlapping peptides ideally suited for PEAKS de novo analysis in a single digestion step.

We are excited to see PEAKS DeepNovo peptide sequencing algorithm efficiently handling the rich fragment ion series from EAciD to delivered high‑confidence peptide sequences and strong residue‑level support across antibody variable regions. Using confident peptide sequences from PEAKS Studio, full antibody sequences—including all CDRs—were reconstructed with higher confidence and fewer errors than conventional workflows.

BSI is proud to support these breakthroughs within our software portfolio, including new support for HTA‑proteases in our automated protein and antibody sequencing tool, PEAKS AB, enabling researchers to confidently sequence peptides from spectra generated by next‑generation fragmentation technologies and extract deeper insights from MS data.

If you’re interested in seeing how this fascinating integration can boost your research, reach out to us today!

Read the full article here: Pañeda, L. P., Kadavá, T., Shamorkina, T. M., Schulte, D., Pribil, P., Heidelberger, S., Narlock-Brand, A. M., Yannone, S. M., Snijder, J., & Heck, A. J. R. (2026). Deep coverage and extended sequence reads obtained with a single archaeal protease expedite de novo protein sequencing by mass spectrometry. Cell Systems. 17, 101536. doi:10.1016/j.cels.2026.101536