Toward Systems Biology
May 30 - 31, June 1, 2011
Grenoble
A Graphical Method for Reducing and Relating Models in Systems Biology
In Systems Biology, an increasing collection of models of various
biological processes is currently developed and made available in
publicly-accessible repositories, such as biomodels.net for instance,
through common exchange formats such as SBML. To date however, there
is no general method to relate different models to each other by
abstraction or reduction relationships, and this task is left to the
modeler for re-using and coupling models at different levels. In
mathematical biology, model reduction techniques have been studied for
a long time, mainly in the case where a model exhibits different time
scales, or different spatial phases, which can be analyzed
separately. These techniques are however far too restrictive to be
applied on a large scale in Systems Biology, and do not take into
account abstractions other than time or phase decompositions. Our
purpose here is to propose a general computational method for relating
models together, by considering primarily the structure of the
interactions and abstracting from their dynamics in a first step.
We present a graph-theoretic formalism with node merge and delete
operations, in which model reductions can be studied as graph matching
problems. From this setting, we derive an algorithm for deciding
whether there exists a reduction from one model to another, and
evaluate it on the computation of the reduction relations between all
SBML models of the biomodels.net repository. In particular in the
case of the numerous models of MAPK signalling, and of the circadian
clock, biologically meaningful mappings between models of each class
are automatically inferred from the structure of the interactions. We
conclude on the generality of our graphical method, on its limits with
respect to the representation of the structure of the interactions in
SBML, and on some perspectives for dealing with the dynamics.
Francois Fages, INRIA Paris-Rocquencourt