title: Novel protein-protein interactions inferred from literature context.
abstract: We have developed a method that predicts Protein-Protein Interactions (PPIs) based on the similarity of the context in which proteins appear in literature. This method outperforms previously developed PPI prediction algorithms that rely on the conjunction of two protein names in MEDLINE abstracts. We show significant increases in coverage (76% versus 32%) and sensitivity (66% versus 41% at a specificity of 95%) for the prediction of PPIs currently archived in 6 PPI databases. A retrospective analysis shows that PPIs can efficiently be predicted before they enter PPI databases and before their interaction is explicitly described in the literature. The practical value of the method for discovery of novel PPIs is illustrated by the experimental confirmation of the inferred physical interaction between CAPN3 and PARVB, which was based on frequent co-occurrence of both proteins with concepts like Z-disc, dysferlin, and alpha-actinin. The relationships between proteins predicted by our method are broader than PPIs, and include proteins in the same complex or pathway. Dependent on the type of relationships deemed useful, the precision of our method can be as high as 90%. The full set of predicted interactions is available in a downloadable matrix and through the webtool Nermal, which lists the most likely interaction partners for a given protein. Our framework can be used for prioritizing potential interaction partners, hitherto undiscovered, for follow-up studies and to aid the generation of accurate protein interaction maps.
authors.affiliation: Biosemantics Association, Department of Human Genetics, Leiden University Medical Center, Leiden, and Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands. hvanhaagen@lumc.nl
authors.forename: Herman H H B M
authors.initials: HH
authors.lastname: van Haagen
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.forename: Alessandro
authors.initials: A
authors.lastname: Botelho Bovo
authors.forename: Antoine
authors.initials: A
authors.lastname: de Morrée
authors.forename: Erik M
authors.initials: EM
authors.lastname: van Mulligen
authors.forename: Christine
authors.initials: C
authors.lastname: Chichester
authors.forename: Jan A
authors.initials: JA
authors.lastname: Kors
authors.forename: Johan T
authors.initials: JT
authors.lastname: den Dunnen
authors.forename: Gert-Jan B
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: Silvère M
authors.initials: SM
authors.lastname: van der Maarel
authors.forename: Vinícius Medina
authors.initials: VM
authors.lastname: Kern
authors.forename: Barend
authors.initials: B
authors.lastname: Mons
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Schuemie
mesh_terms: D000465:Algorithms; D000818:Animals; D002154:Calpain / Q000378:metabolism; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D016239:MEDLINE; D051379:Mice; D015233:Models, Statistical; D009124:Muscle Proteins / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012372:ROC Curve; D011994:Recombinant Proteins / Q000737:chemistry; D015203:Reproducibility of Results; D014481:United States
chemical_list: D009124:Muscle Proteins; D011506:Proteins; D011994:Recombinant Proteins; C105884:CAPN3 protein, human; D002154:Calpain