title: CHRONOS: a time-varying method for microRNA-mediated subpathway enrichment analysis.
abstract: In the era of network medicine and the rapid growth of paired time series mRNA/microRNA expression experiments, there is an urgent need for pathway enrichment analysis methods able to capture the time- and condition-specific 'active parts' of the biological circuitry as well as the microRNA impact. Current methods ignore the multiple dynamical 'themes'-in the form of enriched biologically relevant microRNA-mediated subpathways-that determine the functionality of signaling networks across time.
  
  
  
  To address these challenges, we developed time-vaRying enriCHment integrOmics Subpathway aNalysis tOol (CHRONOS) by integrating time series mRNA/microRNA expression data with KEGG pathway maps and microRNA-target interactions. Specifically, microRNA-mediated subpathway topologies are extracted and evaluated based on the temporal transition and the fold change activity of the linked genes/microRNAs. Further, we provide measures that capture the structural and functional features of subpathways in relation to the complete organism pathway atlas. Our application to synthetic and real data shows that CHRONOS outperforms current subpathway-based methods into unraveling the inherent dynamic properties of pathways.
  
  
  
  CHRONOS is freely available at http://biosignal.med.upatras.gr/chronos/
  
  
  
  tassos.bezerianos@nus.edu.sg
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Computer Engineering and Informatics, Department of Medical Physics, School of Medicine, University of Patras, Patras 26500, Greece.
authors.forename: Aristidis G
authors.initials: AG
authors.lastname: Vrahatis
authors.affiliation: Centre for Cancer Biomarkers CCBIO and Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway and.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Dimitrakopoulou
authors.affiliation: Department of Computer Engineering and Informatics, Department of Medical Physics, School of Medicine, University of Patras, Patras 26500, Greece.
authors.forename: Panos
authors.initials: P
authors.lastname: Balomenos
authors.affiliation: Department of Computer Engineering and Informatics.
authors.forename: Athanasios K
authors.initials: AK
authors.lastname: Tsakalidis
authors.affiliation: Department of Medical Physics, School of Medicine, University of Patras, Patras 26500, Greece, SINAPSE Institute, Center of Life Sciences, National University of Singapore, Singapore 117456.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Bezerianos
mesh_terms: D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs