SpecPeptidOMS Directly and Rapidly Aligns Mass Spectra on Whole Proteomes and Identifies Peptides That Are Not Necessarily Tryptic: Implications for Peptidomics.

Abstract

SpecPeptidOMS directly aligns peptide fragmentation spectra to whole and undigested protein sequences. The algorithm was specifically and initially designed for peptidomics, where the aim is to identify peptides that do not result from the hydrolysis of a known protein and therefore, whose termini cannot be predicted. Thus, SpecPeptidOMS can perform alignments starting and ending anywhere in the protein sequence. The underlying computational method of SpecPeptidOMS, which is based on a dynamic programming approach, was drastically optimized. As a result, SpecPeptidOMS can process around 12,000 spectra per hour on an ordinary laptop, with alignment performed against the entire human proteome. The performance of SpecPeptidOMS was first evaluated on a publicly available data set of (nontryptic) synthetic mass spectra. Accuracy was estimated by considering the results obtained by MaxQuant on the same data set as the "ground truth". A second series of tests on a larger, well-known proteomics data set (HEK293) highlighted SpecPeptidOMS' additional ability to search for open modifications, a feature of interest in peptidomics but also more broadly in conventional proteomics. SpecPeptidOMS is open-source, cross-platform (written in Java), and freely available.