Discovery of phosphorylation motif mixtures in phosphoproteomics data.
BACKGROUND
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.
Ritz
Anna
A
Department of Computer Science, Brown University, Toyota Technological Institute at Chicago, Chicago, IL, USA. aritz@cs.brown.edu
Shakhnarovich
Gregory
G
Salomon
Arthur R
AR
Raphael
Benjamin J
BJ
D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D030562:Databases, Protein; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry*; D010766:Phosphorylation; D040901:Proteomics; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry; D015203:Reproducibility of Results
D010750:Phosphoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases