pSite: Amino Acid Confidence Evaluation for Quality Control of De Novo Peptide Sequencing and Modification Site Localization

peer-reviewed · Journal of Proteome Research · 2017

peer-reviewed · Journal of Proteome Research · 2017. Hao Yang et al. MS-based de novo peptide sequencing has been improved remarkably with significant development of…
Date 2017-12-04
Type peer-reviewed
Venue Journal of Proteome Research
Publisher ACS
Contribution post-processor
DOI 10.1021/acs.jproteome.7b00428
Citations (OpenAlex) 22
Venue 2-year citedness 3.48

Abstract

MS-based de novo peptide sequencing has been improved remarkably with significant development of mass-spectrometry and computational approaches but still lacks quality-control methods. Here we proposed a novel algorithm pSite to evaluate the confidence of each amino acid rather than the full-length peptides obtained by de novo peptide sequencing. A semi-supervised learning approach was used to discriminate correct amino acids from random one; then, an expectation-maximization algorithm was used to adaptively control the false amino-acid rate (FAR). On three test data sets, pSite recalled 86% more amino acids on average than PEAKS at the FAR of 5%. pSite also performed superiorly on the modification site localization problem, which is essentially a special case of amino acid confidence evaluation. On three phosphopeptide data sets, at the false localization rate of 1%, the average recall of pSite was 91% while those of Ascore and phosphoRS were 64 and 63%, respectively. pSite covered 98% of Ascore and phosphoRS results and contributed 21% more phosphorylation sites. Further analyses show that the use of distinct fragmentation features in high-resolution MS/MS spectra, such as neutral loss ions, played an important role in improving the precision of pSite. In summary, the effective and universal model together with the extensive use of spectral information makes pSite an excellent quality control tool for both de novo peptide sequencing and modification site localization.

Authors

  1. Hao Yang · Chinese Academy of Sciences, University of Chinese Academy of Sciences
  2. Hao Chi · Chinese Academy of Sciences, University of Chinese Academy of Sciences
  3. Wen-Jing Zhou · Chinese Academy of Sciences, University of Chinese Academy of Sciences
  4. Wen-Feng Zeng · Chinese Academy of Sciences, University of Chinese Academy of Sciences, Westlake University
  5. Chao Liu · Beihang University, Chinese Academy of Sciences, University of Chinese Academy of Sciences
  6. Rui-Min Wang · Chinese Academy of Sciences, University of Chinese Academy of Sciences
  7. Zhao-Wei Wang · Chinese Academy of Sciences, University of Chinese Academy of Sciences
  8. Xiu-Nan Niu · Chinese Academy of Sciences, University of Chinese Academy of Sciences
  9. Zhen-Lin Chen · Chinese Academy of Sciences, University of Chinese Academy of Sciences
  10. Si-Min He · Chinese Academy of Sciences, University of Chinese Academy of Sciences

Methods and tools

  • pSite: AA confidence + site localization

Cites (14)

Cited by (3)

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