De novo peptide sequencing via tandem mass spectrometry

Peptide sequencing via tandem mass spectrometry (MS/MS) is one of the most powerful tools in proteomics for identifying proteins. Because complete gen ome sequences are accumulating rapidly, the recent trend in interpretation of MS/MS spectra has been database search. However, de novo MS/MS spectral interpretation remains an open problem typically involving manual interpret ation by expert mass spectrometrists. We have developed a new algorithm, SH ERENGA, for de novo interpretation that automatically learns fragment ion t ypes and intensity thresholds from a collection of test spectra generated f rom any type of mass spectrometer, The test data are used to construct opti mal path scoring in the graph representations of MS/MS spectra, A ranked li st of high scoring paths corresponds to potential peptide sequences. SHEREN GA is most useful for interpreting sequences of peptides resulting from unk nown proteins and for validating the results of database search algorithms in fully automated, high-throughput peptide sequencing.