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An iterative statistical approach to the identification of protein phosphorylation motifs from large-scale data sets

Abstract

With the recent exponential increase in protein phosphorylation sites identified by mass spectrometry, a unique opportunity has arisen to understand the motifs surrounding such sites. Here we present an algorithm designed to extract motifs from large data sets of naturally occurring phosphorylation sites. The methodology relies on the intrinsic alignment of phospho-residues and the extraction of motifs through iterative comparison to a dynamic statistical background. Results show the identification of dozens of novel and known phosphorylation motifs from recently published serine, threonine and tyrosine phosphorylation studies. When applied to a linguistic data set to test the versatility of the approach, the algorithm successfully extracted hundreds of language motifs. This method, in addition to shedding light on the consensus sequences of identified and as yet unidentified kinases and modular protein domains, may also eventually be used as a tool to determine potential phosphorylation sites in proteins of interest.

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Figure 1: Overview of motif-building strategy.
Figure 2: Sequence logo representations of various extracted motifs.

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Acknowledgements

The authors thank John Rush and Cell Signaling Technology for providing access to the tyrosine phosphorylation data sets prior to their publication. Additionally, D.S. wishes to thank Michael Chou for assistance with the Moby Dick analysis as well as numerous stimulating conversations regarding the algorithm and critical reading of the manuscript. This work was supported in part by National Institutes of Health grant HG03456 (S.P.G.).

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Correspondence to Daniel Schwartz.

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Schwartz, D., Gygi, S. An iterative statistical approach to the identification of protein phosphorylation motifs from large-scale data sets. Nat Biotechnol 23, 1391–1398 (2005). https://doi.org/10.1038/nbt1146

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