A new way to assign ions in tandem mass spectrometry

Tandem mass spectrometry is a powerful tool in proteomics. By ionizing peptides and then fragmenting those ions into smaller product ions, researchers can determine the biomolecules’ amino acid sequences. But if a sample contains a complex mixture of peptides, it can be challenging to determine which precursor produced which product ions. To avoid such confusion, scientists have implemented other analytical approaches—such as liquid chromatography—to physically separate peptides prior to injection into the mass spectrometer. But trying to fully separate similar peptides using physical approaches can prove futile, and the resulting mix of product ions remains difficult to interpret. Now, an interdisciplinary team of researchers has demonstrated a way to overcome the challenge: use a new technique—dubbed fragment correlation mass spectrometry—on a mix of parent peptides and group product ions based on the noise in their respective signals ( Proc. Natl. Acad. Sci. U.S.A. 2024, DOI: 10.1073 /pnas.2409676121 ). The approach