Motif-All: discovering all phosphorylation motifs

BackgroundPhosphorylation motifs represent common patterns around the phosphorylation site. The discovery of such kinds of motifs reveals the underlying regulation mechanism and facilitates the prediction of unknown phosphorylation event. To date, people have gathered large amounts of phosphorylation data, making it possible to perform substrate-driven motif discovery using data mining techniques.ResultsWe describe an algorithm called Motif-All that is able to efficiently identify all statistically significant motifs. The proposed method explores a support constraint to reduce search space and avoid generating random artifacts. As the number of phosphorylated peptides are far less than that of unphosphorylated ones, we divide the mining process into two stages: The first step generates candidates from the set of phosphorylated sequences using only support constraint and the second step tests the statistical significance of each candidate using the odds ratio derived from the whole data set. Experimental results on real data show that Motif-All outperforms current algorithms in terms of both effectiveness and efficiency.ConclusionsMotif-All is a useful tool for discovering statistically significant phosphorylation motifs. Source codes and data sets are available at: http://bioinformatics.ust.hk/MotifAll.rar.

[1]  Aris Floratos,et al.  Combinatorial pattern discovery in biological sequences: The TEIRESIAS algorithm [published erratum appears in Bioinformatics 1998;14(2): 229] , 1998, Bioinform..

[2]  Gregory Shakhnarovich,et al.  Discovery of phosphorylation motif mixtures in phosphoproteomics data , 2008, Bioinform..

[3]  S. Gygi,et al.  An iterative statistical approach to the identification of protein phosphorylation motifs from large-scale data sets , 2005, Nature Biotechnology.

[4]  Joachim Selbig,et al.  PhosPhAt: a database of phosphorylation sites in Arabidopsis thaliana and a plant-specific phosphorylation site predictor , 2007, Nucleic Acids Res..

[5]  Ramakrishnan Srikant,et al.  Fast Algorithms for Mining Association Rules in Large Databases , 1994, VLDB.

[6]  Rakesh Agarwal,et al.  Fast Algorithms for Mining Association Rules , 1994, VLDB 1994.

[7]  Yu Xue,et al.  PPSP: prediction of PK-specific phosphorylation site with Bayesian decision theory , 2006, BMC Bioinformatics.

[8]  S. Wassertheil-Smoller,et al.  Biostatistics and Epidemiology , 1990, Springer New York.

[9]  George M. Church,et al.  Predicting Protein Post-translational Modifications Using Meta-analysis of Proteome Scale Data Sets*S , 2009, Molecular & Cellular Proteomics.

[10]  Dongsup Kim,et al.  PostMod: sequence based prediction of kinase-specific phosphorylation sites with indirect relationship , 2010, BMC Bioinformatics.

[11]  Robert Schmidt,et al.  PhosPhAt: the Arabidopsis thaliana phosphorylation site database. An update , 2009, Nucleic Acids Res..

[12]  S. Mathivanan,et al.  A curated compendium of phosphorylation motifs , 2007, Nature Biotechnology.