Searching tandem mass spectra against a peptide database requires accurate knowledge of various experimental parameters, including machine settings and details of the sample preparation protocol. In some cases, such as in reanalysis of public data sets, this experimental metadata may be missing or inaccurate. We describe a method for automatically inferring the presence of various types of modifications, including stable-isotope and isobaric labeling and tandem mass tags as well as the enrichment of phosphorylated peptides, directly from a given set of mass spectra. We demonstrate the sensitivity and specificity of the proposed approach, and we provide open-source Python and C++ implementations in a new version of the software tool Param-Medic.
Keywords: database search; isobaric labeling; mass spectrometry; phosphorylation; proteomics; tandem mass tags.