title: On the accuracy and limits of peptide fragmentation spectrum prediction.
abstract: We estimated the reproducibility of tandem mass spectra for the widely used collision-induced dissociation (CID) of peptide ions. Using the Pearson correlation coefficient as a measure of spectral similarity, we found that the within-experiment reproducibility of fragment ion intensities is very high (about 0.85). However, across different experiments and instrument types/setups, the correlation decreases by more than 15% (to about 0.70). We further investigated the accuracy of current predictors of peptide fragmentation spectra and found that they are more accurate than the ad-hoc models generally used by search engines (e.g., SEQUEST) and, surprisingly, approaching the empirical upper limit set by the average across-experiment spectral reproducibility (especially for charge +1 and charge +2 precursor ions). These results provide evidence that, in terms of accuracy of modeling, predicted peptide fragmentation spectra provide a viable alternative to spectral libraries for peptide identification, with a higher coverage of peptides and lower storage requirements. Furthermore, using five data sets of proteome digests by two different proteases, we find that PeptideART (a data-driven machine learning approach) is generally more accurate than MassAnalyzer (an approach based on a kinetic model for peptide fragmentation) in predicting fragmentation spectra but that both models are significantly more accurate than the ad-hoc models.
authors.affiliation: School of Informatics and Computing, Indiana University, Bloomington, Indiana 47408, USA.
authors.forename: Sujun
authors.initials: S
authors.lastname: Li
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Arnold
authors.forename: Haixu
authors.initials: H
authors.lastname: Tang
authors.forename: Predrag
authors.initials: P
authors.lastname: Radivojac
mesh_terms: D034301:Deinococcus / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D010446:Peptide Fragments / Q000032:analysis*; D020543:Proteome / Q000032:analysis; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D020592:Shewanella / Q000737:chemistry
chemical_list: D010446:Peptide Fragments; D020543:Proteome