PTMeta: Increasing identification rates of modified peptides using modification prescanning and meta-analysis

The analysis of peptides and proteins in complex biological systems has greatly improved over the last decade. State-of-the-art mass spectrometric instruments combined with adequate software tools allow for more and more comprehensive proteome analyses. Most proteome-wide studies focus on the analysis of unmodified proteins or look at selected modifications only. However, spectral information of protein modifications, chemically induced through sample preparation or post-translationally attached in biological pathways is acquired as a significant, yet disregarded, fraction of tandem spectra in most discovery studies. We present a new computational pipeline, PTMeta, to uncover information of modifications attached to peptides. We use modification prescanning to pinpoint the most abundant potential modifications, followed by extensive database search and a statistical framework to combine results from database search runs with different modification settings.