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. 2006 Apr 26:7:222.
doi: 10.1186/1471-2105-7-222.

A novel scoring schema for peptide identification by searching protein sequence databases using tandem mass spectrometry data

Zhuo Zhang  1 , Shiwei Sun, Xiaopeng Zhu, Suhua Chang, Xiaofei Liu, Chungong Yu, Dongbo Bu, Runsheng Chen
Affiliations

A novel scoring schema for peptide identification by searching protein sequence databases using tandem mass spectrometry data

Zhuo Zhang et al. BMC Bioinformatics. .

Abstract

Background: Tandem mass spectrometry (MS/MS) is a powerful tool for protein identification. Although great efforts have been made in scoring the correlation between tandem mass spectra and an amino acid sequence database, improvements could be made in three aspects, including characterization ofpeaks in spectra, adoption of effective scoring functions and access to thereliability of matching between peptides and spectra.

Results: A novel scoring function is presented, along with criteria to estimate the performance confidence of the function. Through learning the typesof product ions and the probability of generating them, a hypothetic spectrum was generated for each candidate peptide. Then relative entropy was introduced to measure the similarity between the hypothetic and the observed spectra. Based on the extreme value distribution (EVD) theory, a threshold was chosen to distinguish a true peptide assignment from a random one. Tests on a public MS/MS dataset demonstrated that this method performs better than the well-known SEQUEST.

Conclusion: A reliable identification of proteins from the spectra promises a more efficient application of tandem mass spectrometry to proteomes with high complexity.

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Figures

Figure 1
Figure 1
Schematic figure of peptide fragmentation. A peptide breaks into two parts, induced by the collisional gas. Breakage favors the peptide backbone, resulting in N-terminal a/b/c ions and C-terminal x/y/z/ions; small chemical groups such as water and amino molecules often dissociate from specific residues.
Figure 2
Figure 2
Occurrence probability of different N-terminal ions. In general, serial ions bear a larger probability, however, their variants (like dehydrated form) also often appear. The m/z of the peptide bond is set to 0, and the relative probability is normalized to a total probability of 100.0 (including C-terminal ions, which are not shown).
Figure 3
Figure 3
Breakage preference in the position along peptides. Breakage tends to occur at middle rather than terminal positions of the peptides. The Abscissa denotes the position of residues relative to the whole sequence. The relative probability is normalized to a total of 100.0.
Figure 4
Figure 4
The hypothetic and experimental spectra of the sequence VGDANPALQK. The serial ions are marked with the observed intensity.
Figure 5
Figure 5
Distribution of minimal score values of MS/MS spectra. The score of a spectrum is the best match to the peptide library. The solidcurve results from correlating a set of MS/MS spectra with a peptide library containing the query peptide, while the dashed curve results from matcheswith a library not containing the query at all (i.e. all matches are random). Threshold is set to be the location of the cross-point of the two distributions, which minimizes the sum of false-positives and false-negatives. Therefore, if a match had a score less than 3.8, it was considered highly probable that the spectrum was produced as result of the matched peptide.
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