A perspective toward mass spectrometry-based de novo sequencing of endogenous antibodies
peer-reviewed · mAbs · 2022
| Date | 2022-12-31 |
| Type | peer-reviewed |
| Venue | mAbs |
| Publisher | Informa UK Limited |
| Contribution | review |
| DOI | 10.1080/19420862.2022.2079449 |
| Citations (OpenAlex) | 48 |
Abstract
A key step in therapeutic and endogenous humoral antibody characterization is identifying the amino acid sequence. So far, this task has been mainly tackled through sequencing of B-cell receptor (BCR) repertoires at the nucleotide level. Mass spectrometry (MS) has emerged as an alternative tool for obtaining sequence information directly at the - most relevant - protein level. Although several MS methods are now well established, analysis of recombinant and endogenous antibodies comes with a specific set of challenges, requiring approaches beyond the conventional proteomics workflows. Here, we review the challenges in MS-based sequencing of both recombinant as well as endogenous humoral antibodies and outline state-of-the-art methods attempting to overcome these obstacles. We highlight recent examples and discuss remaining challenges. We foresee a great future for these approaches making de novo antibody sequencing and discovery by MS-based techniques feasible, even for complex clinical samples from endogenous sources such as serum and other liquid biopsies.
Methods and tools
- Endogenous antibody de novo sequencing (perspective): Perspective on reading antibody sequences at the protein level rather than from B-cell receptor repertoires at the nucleotide level, surveying what mass spectrometry can already do for therapeutic antibodies and what endogenous, polyclonal ones still demand.
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Cited by (5)
- Deep coverage and extended sequence reads obtained with a single archaeal protease expedite de novo protein sequencing by mass spectrometry (2026) both
- XA-Novo: an accurate and high-throughput mass spectrometry-based de novo sequencing technology for monoclonal antibodies and antibody mixtures (2026) both
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