title: PDON: Parkinson's disease ontology for representation and modeling of the Parkinson's disease knowledge domain.
abstract: BACKGROUND
  Despite the unprecedented and increasing amount of data, relatively little progress has been made in molecular characterization of mechanisms underlying Parkinson's disease. In the area of Parkinson's research, there is a pressing need to integrate various pieces of information into a meaningful context of presumed disease mechanism(s). Disease ontologies provide a novel means for organizing, integrating, and standardizing the knowledge domains specific to disease in a compact, formalized and computer-readable form and serve as a reference for knowledge exchange or systems modeling of disease mechanism.
  
  
  METHODS
  The Parkinson's disease ontology was built according to the life cycle of ontology building. Structural, functional, and expert evaluation of the ontology was performed to ensure the quality and usability of the ontology. A novelty metric has been introduced to measure the gain of new knowledge using the ontology. Finally, a cause-and-effect model was built around PINK1 and two gene expression studies from the Gene Expression Omnibus database were re-annotated to demonstrate the usability of the ontology.
  
  
  RESULTS
  The Parkinson's disease ontology with a subclass-based taxonomic hierarchy covers the broad spectrum of major biomedical concepts from molecular to clinical features of the disease, and also reflects different views on disease features held by molecular biologists, clinicians and drug developers. The current version of the ontology contains 632 concepts, which are organized under nine views. The structural evaluation showed the balanced dispersion of concept classes throughout the ontology. The functional evaluation demonstrated that the ontology-driven literature search could gain novel knowledge not present in the reference Parkinson's knowledge map. The ontology was able to answer specific questions related to Parkinson's when evaluated by experts. Finally, the added value of the Parkinson's disease ontology is demonstrated by ontology-driven modeling of PINK1 and re-annotation of gene expression datasets relevant to Parkinson's disease.
  
  
  CONCLUSIONS
  Parkinson's disease ontology delivers the knowledge domain of Parkinson's disease in a compact, computer-readable form, which can be further edited and enriched by the scientific community and also to be used to construct, represent and automatically extend Parkinson's-related computable models. A practical version of the Parkinson's disease ontology for browsing and editing can be publicly accessed at http://bioportal.bioontology.org/ontologies/PDON .
authors.affiliation: Department of Bionformatics, Fraunhofer Institute for Algorithms and Scientific Computing, 53754, Sankt Augustin, Germany. erfan.younesi@scai.fraunhofer.de.
authors.forename: Erfan
authors.initials: E
authors.lastname: Younesi
authors.affiliation: Department of Bionformatics, Fraunhofer Institute for Algorithms and Scientific Computing, 53754, Sankt Augustin, Germany. ashutosh.malhotra@scai.fraunhofer.de.|Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn-Aachen International Center for IT, 53113, Bonn, Germany. ashutosh.malhotra@scai.fraunhofer.de.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Malhotra
authors.affiliation: Department of Bionformatics, Fraunhofer Institute for Algorithms and Scientific Computing, 53754, Sankt Augustin, Germany. michaela.guendel@scai-extern.fraunhofer.de.|Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn-Aachen International Center for IT, 53113, Bonn, Germany. michaela.guendel@scai-extern.fraunhofer.de.
authors.forename: Michaela
authors.initials: M
authors.lastname: Gündel
authors.affiliation: Informatics group, UCB Pharma, 208 Bath Road, Slough, UK. phil.scordis@ucb.com.
authors.forename: Phil
authors.initials: P
authors.lastname: Scordis
authors.affiliation: Department of Bionformatics, Fraunhofer Institute for Algorithms and Scientific Computing, 53754, Sankt Augustin, Germany. alpha.tom.kodamullil@scai.fraunhofer.de.|Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn-Aachen International Center for IT, 53113, Bonn, Germany. alpha.tom.kodamullil@scai.fraunhofer.de.
authors.forename: Alpha Tom
authors.initials: AT
authors.lastname: Kodamullil
authors.affiliation: Informatics group, UCB Pharma, 208 Bath Road, Slough, UK. matt.page@ucb.com.
authors.forename: Matt
authors.initials: M
authors.lastname: Page
authors.affiliation: Department of Bionformatics, Fraunhofer Institute for Algorithms and Scientific Computing, 53754, Sankt Augustin, Germany. bernd.mueller@scai.fraunhofer.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Müller
authors.affiliation: Department of Bionformatics, Fraunhofer Institute for Algorithms and Scientific Computing, 53754, Sankt Augustin, Germany. stephan.springstubbe@scai.fraunhofer.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Springstubbe
authors.affiliation: Department of Neurology, University of Bonn, 53105, Bonn, Germany. ullrich.wuellner@ukb.uni-bonn.de.
authors.forename: Ullrich
authors.initials: U
authors.lastname: Wüllner
authors.affiliation: Pharmacology Parkinson's Disease and Movement Disorders, UCB Pharma S.A., Chemin du Foriest, B-1420, Braine-l'Allued, Belgium. dieter.scheller@ucb.com.
authors.forename: Dieter
authors.initials: D
authors.lastname: Scheller
authors.affiliation: Department of Bionformatics, Fraunhofer Institute for Algorithms and Scientific Computing, 53754, Sankt Augustin, Germany. martin.hofmann-apitius@scai.fraunhofer.de.|Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn-Aachen International Center for IT, 53113, Bonn, Germany. martin.hofmann-apitius@scai.fraunhofer.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Hofmann-Apitius
mesh_terms: D000818:Animals; D030541:Databases, Genetic; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D019359:Knowledge; D058977:Molecular Sequence Annotation; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics*; D012984:Software