High-resolution detection of post-translational modifications using single-molecule protein sequencing

AGBT 2026 Poster – Post-translational modifications (PTMs) play a critical role in regulating protein function and cellular processes. However, due to the diversity and complexity of the proteome, methods to detect and quantify PTMs have lagged behind advances in DNA sequencing. While conventional mass spectrometry and antibody-based methods provide valuable information, they are limited in their capacity to resolve and quantify PTMs at the amino acid level, particularly for PTMs with minimal differences in mass and without available antibodies. The Quantum-Si Platinum® and Platinum® Pro sequencers are benchtop instruments designed for high-resolution, single-molecule protein sequencing. These instruments use engineered N-terminal amino acid recognizers to accurately determine the sequence composition of proteins, enabling the detection of PTMs and making advanced proteomic analysis accessible in a standard laboratory setting. In this study, we report the application of this next-gen protein sequencing (NGPS) method to detect and quantify multiple PTMs across diverse protein types.