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 counterintuitive: 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, allows one to separate the prefix and suffix ladders, to greatly reduce the number of noise peaks, and to generate a small number of peptide reconstructions that are very likely to contain the correct one. The MS/MS database search is thus reduced to extremely fast pattern matching (rather than time-consuming matching of spectra against databases). In addition to speed, our approach provides a new paradigm for identifying post-translational modifications. © Springer-Verlag Berlin Heidelberg 2006.
CITATION STYLE
Bandeira, N., Tsur, D., Frank, A., & Pevzner, P. (2006). A new approach to protein identification. In Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) (Vol. 3909 LNBI, pp. 363–378). https://doi.org/10.1007/11732990_31
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