Protein identification false discovery rates for very large proteomics data sets generated by tandem mass spectrometry.
Comprehensive characterization of a proteome is a fundamental goal in proteomics. To achieve saturation coverage of a proteome or specific subproteome via tandem mass spectrometric identification of tryptic protein sample digests, proteomics data sets are growing dramatically in size and heterogeneity. The trend toward very large integrated data sets poses so far unsolved challenges to control the uncertainty of protein identifications going beyond well established confidence measures for peptide-spectrum matches. We present MAYU, a novel strategy that reliably estimates false discovery rates for protein identifications in large scale data sets. We validated and applied MAYU using various large proteomics data sets. The data show that the size of the data set has an important and previously underestimated impact on the reliability of protein identifications. We particularly found that protein false discovery rates are significantly elevated compared with those of peptide-spectrum matches. The function provided by MAYU is critical to control the quality of proteome data repositories and thereby to enhance any study relying on these data sources. The MAYU software is available as standalone software and also integrated into the Trans-Proteomic Pipeline.
Reiter
Lukas
L
Institute of Molecular Biology, University of Zurich, CH-8057 Zurich, Switzerland.
Claassen
Manfred
M
Schrimpf
Sabine P
SP
Jovanovic
Marko
M
Schmidt
Alexander
A
Buhmann
Joachim M
JM
Hengartner
Michael O
MO
Aebersold
Ruedi
R
D000465:Algorithms; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D005189:False Positive Reactions; D007919:Leptospira / Q000378:metabolism; D015233:Models, Statistical; D010455:Peptides / Q000737:chemistry; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012568:Schizosaccharomyces / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*
D010455:Peptides; D020543:Proteome