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The Problem with Peptide Presumption and the Downfall of Target− Decoy False Discovery Rates

Permanent URL:
http://handle.nal.usda.gov/10113/56697
File:
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Abstract:
In proteomics, peptide-tandem mass spectrum match scores and target−decoy database derived false discovery rates (FDR) are confidence indicators describing the quality of individual and sets of tandem mass spectrum matches. A user can impose a standard by prescribing a limit to these values, equivalent to drawing a line that separates better from poorer quality matches. As a result of setting narrower parent ion mass tolerances to reflect the better resolution of modern mass spectrometers, target−decoy derived FDRs can diminish. FDRs lowered this way consequently drive down the lower-limit for peptide-spectrum match score acceptance. Hence, data quality confidence appears to improve even while fragmentation evidence for some spectra remains weak. One negative outcome can be the presumed identification of peptides that do not exist. The options researchers have to improve proteomics data confidence are not panaceas, and there may be no satisfying solution as long as peptides are identified from a circumscribed list of proteins scientists wish to find.
Author(s):
Bret Cooper
Subject(s):
databases , peptides , proteins , proteomics , spectrometers
Source:
Analytical Chemistry 2012 v.84
Language:
English
Year:
2012
Collection:
Journal Articles, USDA Authors, Peer-Reviewed
Rights:
Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.