SpecOMS: A Full Open Modification Search Method Performing All-to-All Spectra Comparisons within Minutes

The analysis of discovery proteomics
experiments relies on algorithms
that identify peptides from their tandem mass spectra. The almost
exhaustive interpretation of these spectra remains an unresolved issue.
At present, an important number of missing interpretations is probably
due to peptides displaying post-translational modifications and variants
that yield spectra that are particularly difficult to interpret. However,
the emergence of a new generation of mass spectrometers that provide
high fragment ion accuracy has paved the way for more efficient algorithms.
We present a new software, SpecOMS, that can handle the computational
complexity of pairwise comparisons of spectra in the context of large
volumes. SpecOMS can compare a whole set of experimental spectra generated
by a discovery proteomics experiment to a whole set of theoretical
spectra deduced from a protein database in a few minutes on a standard
workstation. SpecOMS can ingeniously exploit those capabilities to
improve the peptide identification process, allowing strong competition
between all possible peptides for spectrum interpretation. Remarkably,
this software resolves the drawbacks (i.e., efficiency problems and
decreased sensitivity) that usually accompany open modification searches.
We highlight this promising approach using results obtained from the
analysis of a public human data set downloaded from the PRIDE (PRoteomics
IDEntification) database.