Wild-card search for shotgun proteomics

The standard programs (SEQUEST, Mascot, and X!Tandem) for peptide and protein identification by tandem-MS have a limitation: the user must tell the program exactly which modifications to consider. There are a few programs available for "blind" modification search (e.g., InsPecT or spectral networks analysis), but these programs do not include all the capabilities of the standard tools, so that users currently have to use more than one software package for a thorough analysis of a tandem-MS data set. In this talk, we describe an especially simple way to combine blind modification search with standard search. A wild-card modification allows any integer mass shift to any one residue within a peptide. The wild-card modification is used most effectively in a multi-pass searching strategy.