title: Bridging the layers: towards integration of signal transduction, regulation and metabolism into mathematical models.
abstract: Mathematical modelling is increasingly becoming an indispensable tool for the study of cellular processes, allowing their analysis in a systematic and comprehensive manner. In the vast majority of the cases, models focus on specific subsystems, and in particular describe either metabolism, gene expression or signal transduction. Integrated models that are able to span and interconnect these layers are, by contrast, rare as their construction and analysis face multiple challenges. Such methods, however, would represent extremely useful tools to understand cell behaviour, with application in distinct fields of biological and medical research. In particular, they could be useful tools to study genotype-phenotype mappings, and the way they are affected by specific conditions or perturbations. Here, we review existing computational approaches that integrate signalling, gene regulation and/or metabolism. We describe existing challenges, available methods and point at potentially useful strategies.
authors.affiliation: EMBL-EBI European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SD, Cambridge, UK.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Gonçalves
authors.forename: Joachim
authors.initials: J
authors.lastname: Bucher
authors.forename: Anke
authors.initials: A
authors.lastname: Ryll
authors.forename: Jens
authors.initials: J
authors.lastname: Niklas
authors.forename: Klaus
authors.initials: K
authors.lastname: Mauch
authors.forename: Steffen
authors.initials: S
authors.lastname: Klamt
authors.forename: Miguel
authors.initials: M
authors.lastname: Rocha
authors.forename: Julio
authors.initials: J
authors.lastname: Saez-Rodriguez
mesh_terms: D005786:Gene Expression Regulation; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D015398:Signal Transduction