Advances in tandem mass-spectrometry (MS/MS) steadily increase the rate of generation of MS/MS spectra and make it more computationally challenging to analyze such huge datasets. As a result, the existing approaches that compare spectra against databases are already facing a bottleneck, particularly when interpreting spectra of post-translationally modified peptides. In this paper we introduce a new idea that allows one to perform MS/MS database search ... without ever comparing a spectrum against a database. The idea has two components: experimental and computational. Our experimental idea is counter-intuitive: we propose to intentionally introduce chemical damage to the sample. Although it does not appear to make any sense from the experimental perspective, it creates a large number of "spectral pairs" that, as we show below, open up computational avenues that were never explored before. Having a spectrum of a modified peptide paired with a spectrum of an unmodified peptide...
Nuno Bandeira, Dekel Tsur, Ari Frank, Pavel A. Pev