Directed mass spectrometry: towards hypothesis-driven proteomics

To date, the vast majority of the proteomic data sets collected by mass spectrometry (MS) have been generated by nondirected methods, whereby the identified precursor ions are stochastically selected for sequencing from complex sample mixtures. Recently, new MS approaches have been developed in which the mass spectrometer is directed to select and fragment sets of precursor ions that represent the most informative peptides in a sample mixture. These directed MS methods have shown superior performance for the fast, sensitive, and highly reproducible generation of consistent data sets at low redundancy. In this manuscript we summarize recent technical advances in directed MS and discuss important applications to quantitative proteomics.