A structured approach for the engineering of biochemical network models, illustrated for signalling pathways

Rainer Breitling, David Gilbert*, Monika Heiner, Richard Orton

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

55 Citations (Scopus)
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Abstract

Quantitative models of biochemical networks (signal transduction cascades, metabolic pathways, gene regulatory circuits) are a central component of modern systems biology. Building and managing these complex models is a major challenge that can benefit from the application of formal methods adopted from theoretical computing science. Here we provide a general introduction to the field of formal modelling, which emphasizes the intuitive biochemical basis of the modelling process, but is also accessible for an audience with a background in computing science and/or model engineering. We show how signal transduction cascades can be modelled in a modular fashion, using both a qualitative approachqualitative Petri nets, and quantitative approachescontinuous Petri nets and ordinary differential equations (ODEs). We review the major elementary building blocks of a cellular signalling model, discuss which critical design decisions have to be made during model building, and present a number of novel computational tools that can help to explore alternative modular models in an easy and intuitive manner. These tools, which are based on Petri net theory, offer convenient ways of composing hierarchical ODE models, and permit a qualitative analysis of their behaviour. We illustrate the central concepts using signal transduction as our main example. The ultimate aim is to introduce a general approach that provides the foundations for a structured formal engineering of large-scale models of biochemical networks.

Original languageEnglish
Pages (from-to)404-421
Number of pages18
JournalBriefings in Bioinformatics
Volume9
Issue number5
DOIs
Publication statusPublished - Sep-2008

Keywords

  • systems biology
  • biochemical networks
  • modelling
  • signal transduction
  • Petri nets
  • ordinary differential equations
  • SYSTEMS BIOLOGY
  • PETRI NETS
  • KINASE CASCADE
  • RECEPTOR
  • ULTRASENSITIVITY
  • SIMULATOR
  • DYNAMICS
  • MAPK

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