title: Pathway network inference from gene expression data.
abstract: BACKGROUND
  The development of high-throughput omics technologies enabled genome-wide measurements of the activity of cellular elements and provides the analytical resources for the progress of the Systems Biology discipline. Analysis and interpretation of gene expression data has evolved from the gene to the pathway and interaction level, i.e. from the detection of differentially expressed genes, to the establishment of gene interaction networks and the identification of enriched functional categories. Still, the understanding of biological systems requires a further level of analysis that addresses the characterization of the interaction between functional modules.
  
  
  RESULTS
  We present a novel computational methodology to study the functional interconnections among the molecular elements of a biological system. The PANA approach uses high-throughput genomics measurements and a functional annotation scheme to extract an activity profile from each functional block -or pathway- followed by machine-learning methods to infer the relationships between these functional profiles. The result is a global, interconnected network of pathways that represents the functional cross-talk within the molecular system. We have applied this approach to describe the functional transcriptional connections during the yeast cell cycle and to identify pathways that change their connectivity in a disease condition using an Alzheimer example.
  
  
  CONCLUSIONS
  PANA is a useful tool to deepen in our understanding of the functional interdependences that operate within complex biological systems. We show the approach is algorithmically consistent and the inferred network is well supported by the available functional data. The method allows the dissection of the molecular basis of the functional connections and we describe the different regulatory mechanisms that explain the network's topology obtained for the yeast cell cycle data.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ponzoni
authors.forename: María
authors.initials: M
authors.lastname: Nueda
authors.forename: Sonia
authors.initials: S
authors.lastname: Tarazona
authors.forename: Stefan
authors.initials: S
authors.lastname: Götz
authors.forename: David
authors.initials: D
authors.lastname: Montaner
authors.forename: Julieta
authors.initials: J
authors.lastname: Dussaut
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.forename: Ana
authors.initials: A
authors.lastname: Conesa
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D005943:Gluconeogenesis / Q000235:genetics; D006019:Glycolysis / Q000235:genetics; D010085:Oxidative Phosphorylation; D059748:Proteolysis; D011687:Purines / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D011687:Purines; D025801:Ubiquitin