Artificial decoy spectral libraries for false discovery rate estimation in spectral library searching in proteomics

Journal of Proteome Research
Henry LamRuedi Aebersold

Abstract

The challenge of estimating false discovery rates (FDR) in peptide identification from MS/MS spectra has received increased attention in proteomics. The simple approach of target-decoy searching has become popular with traditional sequence (database) searching methods, but has yet to be practiced in spectral (library) searching, an emerging alternative to sequence searching. We extended this target-decoy searching approach to spectral searching by developing and validating a robust method to generate realistic, but unnatural, decoy spectra. Our method involves randomly shuffling the peptide identification of each reference spectrum in the library, and repositioning each fragment ion peak along the m/z axis to match the fragment ions expected from the shuffled sequence. We show that this method produces decoy spectra that are sufficiently realistic, such that incorrect identifications are equally likely to match real and decoy spectra, a key assumption necessary for decoy counting. This approach has been implemented in the open-source library building software, SpectraST.

References

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Citations

Feb 14, 2013·Journal of Proteome Research·Ling JianAndrew J Link
May 23, 2012·Molecular BioSystems·Adrian GuthalsNuno Bandeira
Jun 3, 2011·Molecular & Cellular Proteomics : MCP·Terry FarrahRuedi Aebersold
Aug 25, 2011·Molecular & Cellular Proteomics : MCP·Jian WangNuno Bandeira
Mar 7, 2013·Molecular & Cellular Proteomics : MCP·Jayantha GunaratneRuedi Aebersold
Sep 9, 2011·Molecular & Cellular Proteomics : MCP·Henry Lam
Nov 28, 2012·BMC Bioinformatics·Kyowon JeongNuno Bandeira
Jul 24, 2012·Amino Acids·Salvatore CappadonaBas van Breukelen
Dec 1, 2012·Expert Review of Proteomics·Marc VaudelLennart Martens
Dec 15, 2015·Journal of Proteome Research·Matthew The, Lukas Käll
Dec 1, 2015·Proteomics·Johannes Griss
Jul 21, 2011·Molecular Systems Biology·Alexander SchmidtRuedi Aebersold
Oct 15, 2013·Proteomics·Paul A Rudnick
May 8, 2014·Nucleic Acids Research·Juan CaballeroGustavo Glusman
Mar 17, 2015·Journal of Proteome Research·Veronika SuniGarry L Corthals
Jan 20, 2015·Nature Methods·Chih-Chiang TsouAlexey I Nesvizhskii
May 17, 2013·Journal of Proteome Research·Wenguang Shao, Henry Lam
Oct 16, 2013·Journal of Proteome Research·Yingwei Hu, Henry Lam
Jul 3, 2013·Journal of Proteome Research·Mingxun Wang, Nuno Bandeira
Sep 7, 2016·Rapid Communications in Mass Spectrometry : RCM·Adelina E Acosta-MartinPierre Lescuyer
Nov 9, 2016·BMC Bioinformatics·Dmitry IschenkoVadim Govorun
Dec 25, 2016·Briefings in Bioinformatics·Yassene Mohammed, Magnus Palmblad
May 3, 2011·Molecular & Cellular Proteomics : MCP·Chia-Yu YenWilliam M Old
Jul 13, 2016·Mass Spectrometry Reviews·Wenguang Shao, Henry Lam
Jan 11, 2020·Journal of Proteome Research·Jordy Evan Sulaiman, Henry Lam
Sep 3, 2018·Cell Systems·Mingxun WangNuno Bandeira
Mar 30, 2021·Journal of the American Society for Mass Spectrometry·Shanshan Guan, Benjamin J Bythell
May 21, 2021·Rapid Communications in Mass Spectrometry : RCM·Daniel P ZolgMartin Frejno
Aug 4, 2021·Journal of Proteome Research·William E FondrieWilliam S Noble
Apr 20, 2011·Journal of Proteome Research·Erik AhrnéMarkus Müller

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