What to do with “one‐hit wonders”?

Global proteomics has been witness to the solutionbased revolution in which mixtures of proteins are digested into peptides prior to fractionation and analysis by mass spectrometry (MS). In stark contrast to gelbased methods, the complexity of the protein mixture is increased rather than decreased prior to MS analysis. This “bottom up” approach makes peptide mapping as a protein identification tool obsolete as a typical MS scan will detect peptides originating from many different proteins. Instead, solution-based global proteomic studies rely on tandem MS to identify peptides, which are then extrapolated as originating from intact proteins. The results as far as the number of proteins identified using solution-based methods are quite impressive, with more than 1000 proteins being routinely identified in such studies [1].