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Mass spectrometrists should search only for peptides they care about

Abstract

Analysis pipelines that assign peptides to shotgun proteomics mass spectra often discard identified spectra deemed irrelevant to the scientific hypothesis being tested. To improve statistical power, I propose that researchers remove irrelevant peptides from the database prior to searching rather than assigning these peptides to spectra and then discarding the matches.

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Figure 1: Boosting statistical power by eliminating irrelevant hypotheses.
Figure 2: Loss of statistical power as a function of database size.

References

  1. Klammer, A.A., Park, C.Y. & Noble, W.S. J. Proteome Res. 8, 2106–2113 (2009).

    Article  CAS  Google Scholar 

  2. Kim, S., Gupta, N. & Pevzner, P.A. J. Proteome Res. 7, 3354–3363 (2008).

    Article  CAS  Google Scholar 

  3. Howbert, J.J. & Noble, W.S. Mol. Cell. Proteomics 13, 2467–2479 (2014).

    Article  CAS  Google Scholar 

  4. Moore, R.E., Young, M.K. & Lee, T.D. J. Am. Soc. Mass Spectrom. 13, 378–386 (2002).

    Article  CAS  Google Scholar 

  5. Elias, J.E. & Gygi, S.P. Nat. Methods 4, 207–214 (2007).

    Article  CAS  Google Scholar 

  6. Pease, B.N. et al. J. Proteome Res. 12, 4028–4045 (2013).

    Article  CAS  Google Scholar 

  7. Foster, M.W. et al. J. Proteome Res. 13, 3722–3732 (2014).

    Article  CAS  Google Scholar 

  8. Bromenshenk, J.J. et al. PLoS ONE 5, e13181 (2010).

    Article  Google Scholar 

  9. Knudsen, G.M. & Chalkley, R.J. PLoS ONE 6, e20873 (2011).

    Article  CAS  Google Scholar 

  10. Foster, L.J. Mol. Cell. Proteomics 10, M110.006387 (2011).

    Article  Google Scholar 

  11. Foster, L.J. Mol. Cell. Proteomics 11, A110.006387-1 (2012).

    Article  Google Scholar 

  12. Keller, A., Nesvizhskii, A.I., Kolker, E. & Aebersold, R. Anal. Chem. 74, 5383–5392 (2002).

    Article  CAS  Google Scholar 

  13. American Society for Biochemistry and Molecular Biology. Revised publication guidelines for documenting the identification and quantification of peptides, proteins, and post-translational modifications by mass spectrometry. Molecular and Cellular Proteomics http://www.mcponline.org/site/misc/peptide_and_protein_identification_guidelines.pdf (2015; accessed 6 April 2015).

  14. Keich, U. & Noble, W.S. J. Proteome Res. 14, 1147–1160 (2015).

    Article  CAS  Google Scholar 

  15. Nesvizhskii, A.I., Keller, A., Kolker, E. & Aebersold, R. Anal. Chem. 75, 4646–4658 (2003).

    Article  CAS  Google Scholar 

  16. Serang, O., MacCoss, M.J. & Noble, W.S. J. Proteome Res. 9, 5346–5357 (2010).

    Article  CAS  Google Scholar 

  17. Cox, J. & Mann, M. Nat. Biotechnol. 26, 1367–1372 (2008).

    Article  CAS  Google Scholar 

  18. Dudoit, S. & van der Laan, M.J. Multiple Testing Procedures with Applications to Genomics (Springer, 2008).

    Book  Google Scholar 

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Acknowledgements

I thank G. Knudsen for providing access to the honeybee data set. This work was funded by US National Institutes of Health awards R01 GM096306 and P41 GM103533.

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Correspondence to William Stafford Noble.

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The author declares no competing financial interests.

Supplementary information

Supplementary texts

Supplementary Methods (PDF 365 kb)

Supplementary Data 1

Reanalyzed Plasmodium data. The zip file contains five files: two lists of tryptic peptides (Plasmodium and human) and three lists of peptide-spectrum matches (Plasmodium, human, and Plasmodium+human). (ZIP 11716 kb)

Supplementary Data 2

Reanalyzed SP-A data. The zip file contains five files: two lists of tryptic peptides (SP_A variants, human proteome) and three lists of peptide-spectrum matches (SP_A, human, SP_A+human). (ZIP 37844 kb)

Supplementary Data 3

Reanalyzed honeybee data. The zip file contains five files: two lists of tryptic peptides (virus and honeybee) and three lists of peptide-spectrum matches (virus, honeybee, virus+honeybee). (ZIP 46845 kb)

Supplementary Data 4

Source data for Figure 1. (ZIP 609 kb)

Supplementary Data 5

Source data for Figure 2. (ZIP 25 kb)

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Noble, W. Mass spectrometrists should search only for peptides they care about. Nat Methods 12, 605–608 (2015). https://doi.org/10.1038/nmeth.3450

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