title: Reaction-contingency based bipartite Boolean modelling.
abstract: BACKGROUND
  Intracellular signalling systems are highly complex, rendering mathematical modelling of large signalling networks infeasible or impractical. Boolean modelling provides one feasible approach to whole-network modelling, but at the cost of dequantification and decontextualisation of activation. That is, these models cannot distinguish between different downstream roles played by the same component activated in different contexts.
  
  
  RESULTS
  Here, we address this with a bipartite Boolean modelling approach. Briefly, we use a state oriented approach with separate update rules based on reactions and contingencies. This approach retains contextual activation information and distinguishes distinct signals passing through a single component. Furthermore, we integrate this approach in the rxncon framework to support automatic model generation and iterative model definition and validation. We benchmark this method with the previously mapped MAP kinase network in yeast, showing that minor adjustments suffice to produce a functional network description.
  
  
  CONCLUSIONS
  Taken together, we (i) present a bipartite Boolean modelling approach that retains contextual activation information, (ii) provide software support for automatic model generation, visualisation and simulation, and (iii) demonstrate its use for iterative model generation and validation.
authors.affiliation: Theoretical Biophysics, Humboldt-Universität zu Berlin, Invalidenstr, 42, Berlin 10115, Germany. max.floettmann@biologie.hu-berlin.de
authors.forename: Max
authors.initials: M
authors.lastname: Flöttmann
authors.forename: Falko
authors.initials: F
authors.lastname: Krause
authors.forename: Edda
authors.initials: E
authors.lastname: Klipp
authors.forename: Marcus
authors.initials: M
authors.lastname: Krantz
mesh_terms: D020935:MAP Kinase Signaling System; D008954:Models, Biological; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000166:cytology; D012984:Software; D049490:Systems Biology / Q000379:methods*