Logical Modeling and Dynamical Analysis of Cellular Networks.
The logical (or logic) formalism is increasingly used to model regulatory and signaling networks. Complementing these applications, several groups contributed various methods and tools to support the definition and analysis of logical models. After an introduction to the logical modeling framework and to several of its variants, we review here a number of recent methodological advances to ease the analysis of large and intricate networks. In particular, we survey approaches to determine model attractors and their reachability properties, to assess the dynamical impact of variations of external signals, and to consistently reduce large models. To illustrate these developments, we further consider several published logical models for two important biological processes, namely the differentiation of T helper cells and the control of mammalian cell cycle.
Computational Systems Biology Team, Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, INSERM U1024, Ecole Normale Supérieure, PSL Research University Paris, France.
Wassim
W
Abou-Jaoudé
Computational Systems Biology Team, Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, INSERM U1024, Ecole Normale Supérieure, PSL Research University Paris, France.
Pauline
P
Traynard
INESC-ID/Instituto Superior Técnico, University of LisbonLisbon, Portugal; Instituto Gulbenkian de CiênciaOeiras, Portugal.
Pedro T
PT
Monteiro
Faculty of Medicine, Joint Research Centre for Computational Biomedicine, RWTH Aachen University Aachen, Germany.
Julio
J
Saez-Rodriguez
Department of Biochemistry, University of Nebraska-Lincoln Lincoln, NE, USA.
Tomáš
T
Helikar
Computational Systems Biology Team, Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, INSERM U1024, Ecole Normale Supérieure, PSL Research University Paris, France.
Denis
D
Thieffry
Instituto Gulbenkian de Ciência Oeiras, Portugal.
Claudine
C
Chaouiya
T cells activation and differentiation; attractors; cell cycle control; discrete dynamics; logical modeling; reachability analysis; regulatory and signaling networks; simulation