PSMtags improve peptide sequencing and throughput in sensitive proteomics

PSMtag substantially increases detection of peptide fragment b-ions, boosting confidence in sequence identification and enhancing de novo sequencing in mass spectrometry-based proteomics.

• Why it matters: Label-free proteomics is hard to scale to thousands of samples per day, and plexDIA increases throughput but lacks mass tags needed for improved peptide detection and sequencing.
• What they did: The team screened a library of 576 compounds, then used the lead PSMtag to enable 9-plexDIA with stable isotopes of carbon, oxygen, and nitrogen.
• The result: With 9-plexDIA, they achieved 1,130 SPD from single-cell-level human proteomes, generating 27,520 protein datapoints versus 3,216 with label-free methods in the same time.