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Mass spectrometrists should search only for peptides they care about

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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.

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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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Authors and Affiliations

  1. William Stafford Noble is in the Department of Genome Sciences and the Department of Computer Science and Engineering, University of Washington, Seattle, Washington, USA.,

    William Stafford Noble

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  1. William Stafford Noble
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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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