||May 7, 2007
||Dr. Denis Thieffry, Universitee de la Mediterranee, Marseille, France
||Logical modelling of genetic regulatory networks
||To understand the behaviour of the complex regulatory network
controlling the mammalian cell cycle, a proper integration of molecular
data into a full-fledge formal dynamical model is ultimately required.
As most available data on regulatory interactions are qualitative,
logical (discrete) modelling offers an interesting framework to
delineate the main dynamical properties of the underlying networks.
Combining graph theoretic concepts and a specific discrete mathematical
formalism, we have developed a software suite, GINsim, which facilitates
the delineation, the simulation and the analysis of complex regulatory
networks . More recently, still on the basis of our generic discrete
formal framework, we have implemented a method to assess the dynamical
roles of specific regulatory circuits, embedded in complex regulatory
networks (demonstrations about the requirement of specific feedback
circuits for specific dynamical properties in the discrete framework can
be found in ).
This qualitative modelling approach has already been already applied to
various biological systems, in particular to the modelling of genetic
modules controlling cell differentiation and pattern formation in the
course of early Drosophila development . We are currently applying it
to the modelling of the molecular networks controlling the eukaryotic
cell cycle  and T-lymphocyte differentiation . An overview of
recent results will be provided to stimulate a discussion on the assets
as well as on the limits of the logical approach.
The logical modelling software GINsim, as well as a model library are
available in a dedicated XML format (GINML) at the url
1. Gonzalez AG, Naldi A, Sanchez L, Thieffry D, Chaouiya C (2006).
GINsim: a software suite for the qualitative modelling, simulation and
analysis of regulatory networks. Biosystems 84: 91-100.
2. Remy E, Ruet P, Thieffry D (2006). Positive or negative regulatory
circuit inference from multilevel dynamics. Lecture Notes in Control and
Information Sciences 341: 263-70.
3. Sa'nchez L, Thieffry D (2003). Segmenting the fly embryo: a logical
analysis of the pair-rule cross-regulatory module. Journal of
theoretical Biology 224: 517-37.
4. Faure' A, Naldi A, Chaouiya C, Thieffry D (2006). Dynamical analysis
of a generic Boolean model for the control of the mammalian cell cycle.
Bioinformatics 22: e124-31.
5. Chaouiya R, Remy E, Thieffry D (2006). Qualitative Petri Net
modelling of genetic networks. Transactions on Computational Systems
Biology 6: 95-112.