title: Large-scale discovery and characterization of protein regulatory motifs in eukaryotes.
abstract: The increasing ability to generate large-scale, quantitative proteomic data has brought with it the challenge of analyzing such data to discover the sequence elements that underlie systems-level protein behavior. Here we show that short, linear protein motifs can be efficiently recovered from proteome-scale datasets such as sub-cellular localization, molecular function, half-life, and protein abundance data using an information theoretic approach. Using this approach, we have identified many known protein motifs, such as phosphorylation sites and localization signals, and discovered a large number of candidate elements. We estimate that ~80% of these are novel predictions in that they do not match a known motif in both sequence and biological context, suggesting that post-translational regulation of protein behavior is still largely unexplored. These predicted motifs, many of which display preferential association with specific biological pathways and non-random positioning in the linear protein sequence, provide focused hypotheses for experimental validation.
authors.affiliation: Department of Molecular Biology, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Lieber
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.forename: Saeed
authors.initials: S
authors.lastname: Tavazoie
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D056890:Eukaryota; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism
chemical_list: D011506:Proteins; D020543:Proteome