TY - JOUR T1 - Pathway network inference from gene expression data. JF - BMC Syst Biol Y1 - 2014 A1 - Ponzoni, Ignacio A1 - Nueda, María A1 - Tarazona, Sonia A1 - Götz, Stefan A1 - Montaner, David A1 - Dussaut, Julieta A1 - Dopazo, Joaquin A1 - Conesa, Ana KW - Alzheimer Disease KW - Cell Cycle KW - DNA Replication KW - Gene Expression Profiling KW - Gene Regulatory Networks KW - Gluconeogenesis KW - Glycolysis KW - Oxidative Phosphorylation KW - Proteolysis KW - Purines KW - Saccharomyces cerevisiae KW - Systems biology KW - Ubiquitin AB -

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.

VL - 8 Suppl 2 U1 - https://www.ncbi.nlm.nih.gov/pubmed/25032889?dopt=Abstract ER -