title: Finding gene regulatory network candidates using the gene expression knowledge base.
abstract: BACKGROUND
  Network-based approaches for the analysis of large-scale genomics data have become well established. Biological networks provide a knowledge scaffold against which the patterns and dynamics of 'omics' data can be interpreted. The background information required for the construction of such networks is often dispersed across a multitude of knowledge bases in a variety of formats. The seamless integration of this information is one of the main challenges in bioinformatics. The Semantic Web offers powerful technologies for the assembly of integrated knowledge bases that are computationally comprehensible, thereby providing a potentially powerful resource for constructing biological networks and network-based analysis.
  
  
  RESULTS
  We have developed the Gene eXpression Knowledge Base (GeXKB), a semantic web technology based resource that contains integrated knowledge about gene expression regulation. To affirm the utility of GeXKB we demonstrate how this resource can be exploited for the identification of candidate regulatory network proteins. We present four use cases that were designed from a biological perspective in order to find candidate members relevant for the gastrin hormone signaling network model. We show how a combination of specific query definitions and additional selection criteria derived from gene expression data and prior knowledge concerning candidate proteins can be used to retrieve a set of proteins that constitute valid candidates for regulatory network extensions.
  
  
  CONCLUSIONS
  Semantic web technologies provide the means for processing and integrating various heterogeneous information sources. The GeXKB offers biologists such an integrated knowledge resource, allowing them to address complex biological questions pertaining to gene expression. This work illustrates how GeXKB can be used in combination with gene expression results and literature information to identify new potential candidates that may be considered for extending a gene regulatory network.
authors.affiliation: Department of Biology, Norwegian University of Science and Technology (NTNU), N-7491, Trondheim, Norway. aravind.venkatesan@ntnu.no.
authors.forename: Aravind
authors.initials: A
authors.lastname: Venkatesan
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7489, Trondheim, Norway. sushil.tripathi@ntnu.no.
authors.forename: Sushil
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Escuela Nacional de Sanidad, Instituto de Salud Carlos III, 28029, Madrid, Spain. asdgvarela@gmail.com.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanz de Galdeano
authors.affiliation: Department of Biology, Norwegian University of Science and Technology (NTNU), N-7491, Trondheim, Norway. w.blonde@vumc.nl.
authors.forename: Ward
authors.initials: W
authors.lastname: Blondé
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7489, Trondheim, Norway. astrid.lagreid@ntnu.no.
authors.forename: Astrid
authors.initials: A
authors.lastname: Lægreid
authors.affiliation: Department of Biology, Norwegian University of Science and Technology (NTNU), N-7491, Trondheim, Norway. vladimir.mironov@ntnu.no.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mironov
authors.affiliation: Department of Biology, Norwegian University of Science and Technology (NTNU), N-7491, Trondheim, Norway. martin.kuiper@ntnu.no.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuiper
mesh_terms: D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods*; D006801:Humans; D051188:Knowledge Bases; D008954:Models, Biological; D060066:Protein Interaction Maps; D012660:Semantics; D015398:Signal Transduction