Journal Article

Discovery of phosphorylation motif mixtures in phosphoproteomics data

Anna Ritz, Gregory Shakhnarovich, Arthur R. Salomon and Benjamin J. Raphael

in Bioinformatics

Volume 25, issue 1, pages 14-21
Published in print January 2009 | ISSN: 1367-4803
Published online November 2008 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/btn569
Discovery of phosphorylation motif mixtures in phosphoproteomics data

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Motivation: Modification of proteins via phosphorylation is a primary mechanism for signal transduction in cells. Phosphorylation sites on proteins are determined in part through particular patterns, or motifs, present in the amino acid sequence.

Results: We describe an algorithm that simultaneously discovers multiple motifs in a set of peptides that were phosphorylated by several different kinases. Such sets of peptides are routinely produced in proteomics experiments.Our motif-finding algorithm uses the principle of minimum description length to determine a mixture of sequence motifs that distinguish a foreground set of phosphopeptides from a background set of unphosphorylated peptides. We show that our algorithm outperforms existing motif-finding algorithms on synthetic datasets consisting of mixtures of known phosphorylation sites. We also derive a motif specificity score that quantifies whether or not the phosphoproteins containing an instance of a motif have a significant number of known interactions. Application of our motif-finding algorithm to recently published human and mouse proteomic studies recovers several known phosphorylation motifs and reveals a number of novel motifs that are enriched for interactions with a particular kinase or phosphatase. Our tools provide a new approach for uncovering the sequence specificities of uncharacterized kinases or phosphatases.

Availability: Software is available at http:/cs.brown.edu/people/braphael/software.html.

Contact: aritz@cs.brown.edu; braphael@cs.brown.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Journal Article.  6362 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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