title: ChainRank, a chain prioritisation method for contextualisation of biological networks.
abstract: BACKGROUND
  Advances in high throughput technologies and growth of biomedical knowledge have contributed to an exponential increase in associative data. These data can be represented in the form of complex networks of biological associations, which are suitable for systems analyses. However, these networks usually lack both, context specificity in time and space as well as the distinctive borders, which are usually assigned in the classical pathway view of molecular events (e.g. signal transduction). This complexity and high interconnectedness call for automated techniques that can identify smaller targeted subnetworks specific to a given research context (e.g. a disease scenario).
  
  
  RESULTS
  Our method, named ChainRank, finds relevant subnetworks by identifying and scoring chains of interactions that link specific network components. Scores can be generated from integrating multiple general and context specific measures (e.g. experimental molecular data from expression to proteomics and metabolomics, literature evidence, network topology). The performance of the novel ChainRank method was evaluated on recreating selected signalling pathways from a human protein interaction network. Specifically, we recreated skeletal muscle specific signaling networks in healthy and chronic obstructive pulmonary disease (COPD) contexts. The analysis showed that ChainRank can identify main mediators of context specific molecular signalling. An improvement of up to factor 2.5 was shown in the precision of finding proteins of the recreated pathways compared to random simulation.
  
  
  CONCLUSIONS
  ChainRank provides a framework, which can integrate several user-defined scores and evaluate their combined effect on ranking interaction chains linking input data sets. It can be used to contextualise networks, identify signaling and regulatory path amongst targeted genes or to analyse synthetic lethality in the context of anticancer therapy. ChainRank is implemented in R programming language and freely available at https://github.com/atenyi/ChainRank.
authors.affiliation: Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Research Institute, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain. tenyi.akos@ub.edu.|Centro de Investigación en Red de Enfermedades Respiratorias (CibeRes), 07110, Palma de Mallorca, Spain. tenyi.akos@ub.edu.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Tényi
authors.affiliation: Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Research Institute, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain. pde_atauri@ub.edu.|Departament de Bioquimica i Biologia Molecular, Facultat de Biologia-IBUB, Universitat de Barcelona, 08028, Barcelona, Spain. pde_atauri@ub.edu.
authors.forename: Pedro
authors.initials: P
authors.lastname: de Atauri
authors.affiliation: Unit of computational Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institute and Karolinska University Hospital, SE-171 76, Stockholm, Sweden. david.gomezcabrero@ki.se.
authors.forename: David
authors.initials: D
authors.lastname: Gomez-Cabrero
authors.affiliation: Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Research Institute, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain. iscano@clinic.ub.es.|Centro de Investigación en Red de Enfermedades Respiratorias (CibeRes), 07110, Palma de Mallorca, Spain. iscano@clinic.ub.es.
authors.forename: Isaac
authors.initials: I
authors.lastname: Cano
authors.affiliation: Integrative Systems Biology, University of Liverpool, L69 3BX, Liverpool, UK. kim.clarke@liverpool.ac.uk.
authors.forename: Kim
authors.initials: K
authors.lastname: Clarke
authors.affiliation: Integrative Systems Biology, University of Liverpool, L69 3BX, Liverpool, UK. f.falciani@liverpool.ac.uk.
authors.forename: Francesco
authors.initials: F
authors.lastname: Falciani
authors.affiliation: Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Research Institute, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain. martacascante@ub.edu.|Departament de Bioquimica i Biologia Molecular, Facultat de Biologia-IBUB, Universitat de Barcelona, 08028, Barcelona, Spain. martacascante@ub.edu.
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
authors.affiliation: Hospital Clínic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Research Institute, Universitat de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain. jroca@clinic.ub.es.|Centro de Investigación en Red de Enfermedades Respiratorias (CibeRes), 07110, Palma de Mallorca, Spain. jroca@clinic.ub.es.
authors.forename: Josep
authors.initials: J
authors.lastname: Roca
authors.affiliation: Biomax Informatics AG, D-82152, Planegg, Germany. dieter.maier@biomax.com.
authors.forename: Dieter
authors.initials: D
authors.lastname: Maier
mesh_terms: D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D055432:Metabolomics; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism; D060066:Protein Interaction Maps; D011506:Proteins; D040901:Proteomics / Q000379:methods*; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D015398:Signal Transduction
chemical_list: D011506:Proteins