Protein phosphorylation prediction: limitations, merits and pitfalls

Dimitrios Vlachakis, Elena Bencurova, Louis Papageorgiou, Mangesh Bhide, Sophia Kossida

Abstract


Protein phosphorylation is a major protein post-translational modification process that plays a pivotal role in numerous cellular processes, such as recognition, signaling or degradation. It can be studied experimentally by various methodologies, including western blot analysis, site-directed mutagenesis, 2D gel electrophoresis, mass spectrometry etc. A number of in silico tools have also been developed in order to predict plausible phosphorylation sites in a given protein. In this review, we conducted a benchmark study including the leading protein phosphorylation prediction software, in an effort to determine which performs best. The first place was taken by GPS 2.2, having predicted all phosphorylation sites with a 83% fidelity while in second place came NetPhos 2.0 with 69%.

 

 


Keywords


Bioinformatics; Protein Phosphorylation; Post-Translational Modifications; Benchmark; Phosphorylation Prediction; GPS; NetPhos; Phospho.ELM; PPSP; SMALI; ScanSite; Musite; NetPhos

References


Bandeira N 2011 Protein identification by spectral networks analysis. Methods Mol Biol 694 151-168

Blom, N, Gammeltoft S & Brunak S 1999 Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J Mol Biol 294 1351-1362

Blom N, Sicheritz-Pontén T, Gupta R, Gammeltoft S & Brunak S 2004 Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 4 1633-1649

Ciesla J, Fraczyk T & Rode W 2011 Phosphorylation of basic amino acid residues in proteins: important but easily missed. Acta Biochim Pol 58 137-148

Craig R & Beavis RC 2004 TANDEM: matching proteins with tandem mass spectra. Bioinformatics 20 1466-1467

Dinkel H, Chica C, Via A, Gould CM, Jensen LJ, Gibson TJ & Diella F 2011 Phospho.ELM: a database of phosphorylation sites--update 2011. Nucleic Acids Res 39 D261-267

Gao J, Thelen JJ, Dunker AK & Xu D 2010 Musite, a tool for global prediction of general and kinase-specific phosphorylation sites. Mol Cell Proteomics 9 2586-2600

Geer LY, Markey SP, Kowalak JA, Wagner L, Xu M, Maynard DM, Yang X, Shi W & Bryant SH 2004 Open mass spectrometry search algorithm. J Proteome Res 3 958-964

Leitner A, Sturm M & Lindner W 2011 Tools for analyzing the phosphoproteome and other phosphorylated biomolecules: a review. Anal Chim Acta 703 19-30

Lew DJ & Kornbluth S 1996 Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control. Curr Opin Cell Biol 8 795-804

Li L, Wu C, Huang H, Zhang K, Gan J & Li SS 2008 Prediction of phosphotyrosine signaling networks using a scoring matrix-assisted ligand identification approach. Nucleic Acids Res 36 3263-3273

Lovrić J, Dammeier S, Kieser A, Mischak H & Kolch W 1998 Activated raf induces the hyperphosphorylation of stathmin and the reorganization of the microtubule network. J Biol Chem 273 22848-22855

MacKeigan JP, Murphy LO & Blenis J 2005 Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance. Nat Cell Biol 7 591-600

Masumoto H, Muramatsu S, Kamimura Y & Araki H 2002 S-Cdk-dependent phosphorylation of Sld2 essential for chromosomal DNA replication in budding yeast. Nature 415 651-655

Obenauer JC, Cantley LC & Yaffe MB 2003 Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs. Nucleic Acids Res 31 3635-3641

Ruvolo PP, Deng X & May WS 2001 Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia 15 515-522

Song C, Ye M, Liu Z, Cheng H, Jiang X, Han G, Songyang Z, Tan Y, Wang H, Ren J, Xue Y & Zou H 2012 Systematic analysis of protein phosphorylation networks from phosphoproteomic data. Mol Cell Proteomics 11 1070-1083

St-Denis N & Gingras AC 2012 Mass spectrometric tools for systematic analysis of protein phosphorylation. Prog Mol Biol Transl Sci 106 3-32

Sundstrom JM, Sundstrom CJ, Sundstrom SA, Fort PE, Rauscher RL, Gardner TW & Antonetti DA 2009 Phosphorylation site mapping of endogenous proteins: a combined MS and bioinformatics approach. J Proteome Res 8 798-807

Suter B, Graham C & Stagljar I 2008 Exploring protein phosphorylation in response to DNA damage using differentially tagged yeast arrays. Biotechniques 45 581-584

Tabb DL, Saraf A & Yates JR 3rd 2003 GutenTag: high-throughput sequence tagging via an empirically derived fragmentation model. Anal Chem 75 6415-6421

Tanner S, Shu H, Frank A, Wang LC, Zandi E, Mumby M, Pevzner PA & Bafna V 2005 InsPecT: identification of posttranslationally modified peptides from tandem mass spectra. Anal Chem 77 4626-4639

Xue Y, Li A, Wang L, Feng H & Yao X 2006 PPSP: prediction of PK-specific phosphorylation site with Bayesian decision theory. BMC Bioinformatics 7 163

Xue Y, Ren J, Gao X, Jin C, Wen L & Yao X 2008 GPS 2.0, a tool to predict kinase-specific phosphorylation sites in hierarchy. Mol Cell Proteomics 7 1598-1608

Xue Y, Zhou F, Zhu M, Ahmed K, Chen G & Yao X 2005 GPS: a comprehensive www server for phosphorylation sites prediction. Nucleic Acids Res 33 W184-187

Yates JR 3rd, Eng JK, McCormack AL & Schieltz D 1995 Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. Anal Chem 67 1426-1436

Zhou FF, Xue Y, Chen GL & Yao X 2004 GPS: a novel group-based phosphorylation predicting and scoring method. Biochem Biophys Res Commun 325 1443-1448

Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, Bertone P, Lan N, Jansen R, Bidlingmaier S, Houfek T, Mitchell T, Miller P, Dean RA, Gerstein M & Snyder M 2001 Global analysis of protein activities using proteome chips. Science 293 2101-2105


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