InsPecT: Identification of Posttranslationally Modified Peptides from Tandem Mass Spectra.

Reliable identification of posttranslational modifications is key to understanding various cellular regulatory processes. We describe a tool, InsPecT, to identify post-translational modifications using tandem mass specirom- etry data. InsPecT constructs database filters that proved to be very successful in genomics searches. Given an MS/MS spectrum S and a database D, a database filter selects a small fraction of database D that is guaranteed (with high probability) to contain a peptide that produced S. InsPecT uses peptide sequence tags as efficient filters that reduce the size of the database by a few orders of magnitude while retaining the correct peptide with very high probability. In addition to ifitering, InsPecT also uses novel algorithms for scoring and validating in the presence of modifications, without explicit enumeration of all vari- ants. InsPecT identifies modified peptides with better or equivalent accuracy than other database search tools while being 2 orders of magnitude faster than SEQ UEST, and substantially faster than X!TANDEM on complex mixtures. The tool was used to identify a number of novel modifications in different data sets, including many phos- phopetides in data provided by Alliance for Cellular Signaling that were missed by other tools. [ABSTRACT FROM AUTHOR]