Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2011 Apr 1;10(4):2123-7.
doi: 10.1021/pr101143m. Epub 2011 Feb 21.

Comment on "Unbiased statistical analysis for multi-stage proteomic search strategies"

Marshall Bern  1 , Yong J Kil
Affiliations
Comment

Comment on "Unbiased statistical analysis for multi-stage proteomic search strategies"

Marshall Bern et al. J Proteome Res. .

Abstract

Everett et al. recently reported on a statistical bias that arises in the target-decoy approach to false discovery rate estimation in two-pass proteomics search strategies as exemplified by X!Tandem. This bias can cause serious underestimation of the false discovery rate. We argue here that the "unbiased" solution proposed by Everett et al., however, is also biased and under certain circumstances can also result in a serious underestimate of the FDR, especially at the protein level.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Results of five two-stage ByOnic searches of the Aurum spectra (MALDI-TOF-TOF spectra of reference proteins) against a nonsense protein database containing no true proteins. EV shows the substantial bias of Everett et al.'s proposed solution when the multi-stage search does not use the matched spectrum removal step. EMSR shows the mild bias of the proposed solution when the MSR step is used. XT, XMSR, and BK do not show any bias in this nonsense-database experiment.
Figure 2
Figure 2
Results of six ByOnic searches of the Aurum spectra against a good protein database. EV and XT are two-stage searches biased in quality and quantity respectively. BK is a two-stage search using decoys matched in both quality and quantity. 1PASS is a one-stage search using the most widely accepted target-decoy approach. XMSR and EMSR are two-stage searches with the matched spectrum removal step.
Figure 3
Figure 3
Results of three X!Tandem searches of the Aurum spectra against a good protein database. All searches used X!Tandem's matched spectrum removal step with acceptance criterion E-value 0.1 or better. EMSR and XMSR are two-stage searches biased in quality and quantity respectively. BKMSR is a two-stage search using decoys matched in both quality and quantity.
See this image and copyright information in PMC

Comment on

References

    1. Bern M, Goldberg D. Improved ranking functions for protein and modification-site identifications. J Comp Biology. 2008;15:705–719. - PubMed
    1. Creasy DM, Cottrell JS. Error tolerant searching of uninterpreted tandem mass spectrometry data. Proteomics. 2002;2(10):1426–1434. - PubMed
    1. Nesvizhskii AI, Roos FF, Grossmann J, Vogelzang M, Eddes JS, Gruissem W, Baginsky S, Aebersold R. Dynamic spectrum quality assessment and iterative computational analysis of shotgun proteomic data: toward more efficient identification of posttranslational modifications, sequence polymorphisms, and novel peptides. Mol Cell Proteomics. 2006;5(4):652–670. - PubMed
    1. Craig R, Beavis RC. TANDEM: matching proteins with tandem mass spectra. Bioinformatics. 2004;20(9):1466–1467. - PubMed
    1. Shilov IV, Seymour SL, Patel AA, Loboda A, Tang WH, Keating SP, Hunter CL, Nuwaysir LM, Schaeffer DA. The Paragon Algorithm, a next generation search engine that uses sequence temperature values and feature probabilities to identify peptides from tandem mass spectra. Mol Cell Proteomics. 2007;6:1638–1655. - PubMed

Publication types