title: NeuroRDF: semantic integration of highly curated data to prioritize biomarker candidates in Alzheimer's disease.
abstract: BACKGROUND
  Neurodegenerative diseases are incurable and debilitating indications with huge social and economic impact, where much is still to be learnt about the underlying molecular events. Mechanistic disease models could offer a knowledge framework to help decipher the complex interactions that occur at molecular and cellular levels. This motivates the need for the development of an approach integrating highly curated and heterogeneous data into a disease model of different regulatory data layers. Although several disease models exist, they often do not consider the quality of underlying data. Moreover, even with the current advancements in semantic web technology, we still do not have cure for complex diseases like Alzheimer's disease. One of the key reasons accountable for this could be the increasing gap between generated data and the derived knowledge.
  
  
  RESULTS
  In this paper, we describe an approach, called as NeuroRDF, to develop an integrative framework for modeling curated knowledge in the area of complex neurodegenerative diseases. The core of this strategy lies in the usage of well curated and context specific data for integration into one single semantic web-based framework, RDF. This increases the probability of the derived knowledge to be novel and reliable in a specific disease context. This infrastructure integrates highly curated data from databases (Bind, IntAct, etc.), literature (PubMed), and gene expression resources (such as GEO and ArrayExpress). We illustrate the effectiveness of our approach by asking real-world biomedical questions that link these resources to prioritize the plausible biomarker candidates. Among the 13 prioritized candidate genes, we identified MIF to be a potential emerging candidate due to its role as a pro-inflammatory cytokine. We additionally report on the effort and challenges faced during generation of such an indication-specific knowledge base comprising of curated and quality-controlled data.
  
  
  CONCLUSIONS
  Although many alternative approaches have been proposed and practiced for modeling diseases, the semantic web technology is a flexible and well established solution for harmonized aggregation. The benefit of this work, to use high quality and context specific data, becomes apparent in speculating previously unattended biomarker candidates around a well-known mechanism, further leveraged for experimental investigations.
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53754, Sankt Augustin, Germany.|Bonn-Aachen International Center for Information Technology, Rheinische Friedrich-Wilhelms-Universität Bonn, 53113, Bonn, Germany.
authors.forename: Anandhi
authors.initials: A
authors.lastname: Iyappan
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53754, Sankt Augustin, Germany. shweta.bagewadi@scai.fraunhofer.de.|Bonn-Aachen International Center for Information Technology, Rheinische Friedrich-Wilhelms-Universität Bonn, 53113, Bonn, Germany. shweta.bagewadi@scai.fraunhofer.de.
authors.forename: Shweta Bagewadi
authors.initials: SB
authors.lastname: Kawalia
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53754, Sankt Augustin, Germany.|University of Applied Sciences Koblenz, RheinAhrCampus, Joseph-Rovan-Allee 2, 53424, Remagen, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Raschka
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53754, Sankt Augustin, Germany.|Bonn-Aachen International Center for Information Technology, Rheinische Friedrich-Wilhelms-Universität Bonn, 53113, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hofmann-Apitius
authors.affiliation: Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53754, Sankt Augustin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Senger
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D064229:Biological Ontologies; D015415:Biomarkers / Q000378:metabolism*; D057225:Data Mining; D020869:Gene Expression Profiling; D006801:Humans; D012660:Semantics
chemical_list: D015415:Biomarkers
keywords: Alzheimer's disease; Data curation; Data harmonization; Data integration; Disease modeling; Neurodegenerative diseases; RDF; Semantic web