Partial covariance two-dimensional mass spectrometry for bio-molecular primary structure

A new kind of two-dimensional mass spectrometry is described and applied to peptides, proteins and oligonucleotides. Partial covariance two-dimensional mass spectrometry (pC-2DMS) detects intrinsic statistical correlations between bio-molecular fragments originating from the same or consecutive decomposition events. This enables the identification of pairs of ions sharing a common origin across the entire fragment mass spectrum. The fragment-fragment correlations revealed by pC-2DMS are much more specific to the bio-molecular primary structure and its modifications than the individual fragment mass-to-charge ratios on which standard one-dimensional mass spectrometry (MS) is based. We illustrate the analytical power of pC-2DMS by demonstrating the identification of mixtures of combinatorial post-translational modification patterns inaccessible to standard MS.