Modeling and Simulation Tools: From Systems Biology to Systems Medicine

  • Brett G. Olivier
  • Maciej J. Swat
  • Martijn J. Moné
Part of the Methods in Molecular Biology book series (MIMB, volume 1386)


Modeling is an integral component of modern biology. In this chapter we look into the role of the model, as it pertains to Systems Medicine, and the software that is required to instantiate and run it. We do this by comparing the development, implementation, and characteristics of tools that have been developed to work with two divergent methodologies: Systems Biology and Pharmacometrics. From the Systems Biology perspective we consider the concept of “Software as a Medical Device” and what this may imply for the migration of research-oriented, simulation software into the domain of human health.

In our second perspective, we see how in practice hundreds of computational tools already accompany drug discovery and development at every stage of the process. Standardized exchange formats are required to streamline the model exchange between tools, which would minimize translation errors and reduce the required time. With the emergence, almost 15 years ago, of the SBML standard, a large part of the domain of interest is already covered and models can be shared and passed from software to software without recoding them. Until recently the last stage of the process, the pharmacometric analysis used in clinical studies carried out on subject populations, lacked such an exchange medium. We describe a new emerging exchange format in Pharmacometrics which covers the non-linear mixed effects models, the standard statistical model type used in this area. By interfacing these two formats the entire domain can be covered by complementary standards and subsequently the according tools.

Key words

Systems biology Software design Standards development SBML Kinetic modeling Constraint-based modeling Quantitative and systems pharmacology Physiology-based pharmacokinetics Pharmacodynamics Pharmacometrics 



Brett Olivier is supported by a BE-Basic Foundation grant F08.005.001. Maciej Swat has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115156, resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. The DDMoRe project is also supported by financial contribution from academic and SME partners.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Brett G. Olivier
    • 1
  • Maciej J. Swat
    • 2
  • Martijn J. Moné
    • 3
    • 4
  1. 1.Systems BioinformaticsVU University AmsterdamAmsterdamThe Netherlands
  2. 2.EMBL-European Bioinformatics InstituteWellcome Trust Genome CampusHinxtonUK
  3. 3.Molecular Cell PhysiologyVU University AmsterdamAmsterdamThe Netherlands
  4. 4.Systems and Synthetic BiologyWageningen UniversityWageningenThe Netherlands

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