title: Global investigation of protein-protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences.
abstract: Protein-protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of approximately 99.95% and executes 16,000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29,589 high confidence interactions of approximately 2 x 10(7) possible pairs. Of these, 14,438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations.
authors.affiliation: School of Computer Science, Carleton University, Ottawa, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Pitre
authors.forename: C
authors.initials: C
authors.lastname: North
authors.forename: M
authors.initials: M
authors.lastname: Alamgir
authors.forename: M
authors.initials: M
authors.lastname: Jessulat
authors.forename: A
authors.initials: A
authors.lastname: Chan
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.forename: J R
authors.initials: JR
authors.lastname: Green
authors.forename: M
authors.initials: M
authors.lastname: Dumontier
authors.forename: F
authors.initials: F
authors.lastname: Dehne
authors.forename: A
authors.initials: A
authors.lastname: Golshani
mesh_terms: D019295:Computational Biology / Q000379:methods*; D016681:Genome, Fungal; D010455:Peptides / Q000737:chemistry; D025941:Protein Interaction Mapping / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D020539:Sequence Analysis, Protein
chemical_list: D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins