Accurate annotation of peptide modifications through unrestrictive database search.
Proteins are extensively modified after translation due to cellular regulation, signal transduction, or chemical damage. Peptide tandem mass spectrometry can discover post-translational modifications, as well as sequence polymorphisms. Recent efforts have studied modifications at the proteomic scale. In this context, it becomes crucial to assess the accuracy of modification discovery. We discuss methods to quantify the false discovery rate from a search and demonstrate how several features can be used to distinguish valid modifications from search artifacts. We present a tool, PTMFinder, which implements these methods. We summarize the corpus of post-translational modifications identified on large data sets. Thousands of known and novel modification sites are identified, including site-specific modifications conserved over vast evolutionary distances.
Tanner
Stephen
S
Bioinformatics Program, University of California San Diego, La Jolla, California 92093, USA. stanner@ucsd.edu
Payne
Samuel H
SH
Dasari
Surendra
S
Shen
Zhouxin
Z
Wilmarth
Phillip A
PA
David
Larry L
LL
Loomis
William F
WF
Briggs
Steven P
SP
Bafna
Vineet
V
D030562:Databases, Protein; D016247:Information Storage and Retrieval; D010455:Peptides / Q000737:chemistry; D011110:Polymorphism, Genetic; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry*; D012984:Software; D053719:Tandem Mass Spectrometry
D010455:Peptides; D011506:Proteins