title: Assignment of protein function and discovery of novel nucleolar proteins based on automatic analysis of MEDLINE.
abstract: Attribution of the most probable functions to proteins identified by proteomics is a significant challenge that requires extensive literature analysis. We have developed a system for automated prediction of implicit and explicit biologically meaningful functions for a proteomics study of the nucleolus. This approach uses a set of vocabulary terms to map and integrate the information from the entire MEDLINE database. Based on a combination of cross-species sequence homology searches and the corresponding literature, our approach facilitated the direct association between sequence data and information from biological texts describing function. Comparison of our automated functional assignment to manual annotation demonstrated our method to be highly effective. To establish the sensitivity, we defined the functional subtleties within a family containing a highly conserved sequence. Clustering of the DEAD-box protein family of RNA helicases confirmed that these proteins shared similar morphology although functional subfamilies were accurately identified by our approach. We visualized the nucleolar proteome in terms of protein functions using multi-dimensional scaling, showing functional associations between nucleolar proteins that were not previously realized. Finally, by clustering the functional properties of the established nucleolar proteins, we predicted novel nucleolar proteins. Subsequently, nonproteomics studies confirmed the predictions of previously unidentified nucleolar proteins.
authors: Biosemantics Group, Medical Informatics Department, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Martijn
authors: M
authors: Schuemie
authors: Christine
authors: C
authors: Chichester
authors: Frederique
authors: F
authors: Lisacek
authors: Yohann
authors: Y
authors: Coute
authors: Peter-Jan
authors: PJ
authors: Roes
authors: Jean Charles
authors: JC
authors: Sanchez
authors: Jan
authors: J
authors: Kors
authors: Barend
authors: B
authors: Mons
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D030562:Databases, Protein; D006801:Humans; D016239:MEDLINE; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020543:Proteome
chemical_list: D009687:Nuclear Proteins; D020543:Proteome; D053487:DEAD-box RNA Helicases