Papers by Claudine Chaouiya
The development of specific computational approaches is needed to analyse the complex regulatory ... more The development of specific computational approaches is needed to analyse the complex regulatory networks that control crucial cellular processes. The complexity of these systems increases even more when cell-cell communication is involved, which is the case in most developmental processes such as epithelial pattern formation. We present EpiLog, a Java software for qualitative simulations of epithelial patterning that combines logical modelling, as implemented in the software GINsim (www.ginsim.org) and cellular automata. Thanks to a user-friendly interface, the modeller loads a single cell model, defines the rules governing inter-cellular signalling and defines the initial conditions. Then, the simulation can be launched and the consecutive steps towards the final pattern are displayed. With EpiLog it is possible, beyond the study of the wild type situation, to perform in silico perturbation experiments (mutations and clonal analyses). The capabilities of Epilog are demonstrated th...
Cancer Research, 2015
Relationships between genetic alterations, such as co-occurrence or mutual exclusivity, are often... more Relationships between genetic alterations, such as co-occurrence or mutual exclusivity, are often observed in cancer, where their understanding may provide new insights into etiology and clinical management. In this study, we combined statistical analyses and computational modelling to explain patterns of genetic alterations seen in 178 patients with bladder tumours (either muscle-invasive or non-muscle-invasive). A statistical analysis on frequently altered genes identified pair associations including co-occurrence or mutual exclusivity. Focusing on genetic alterations of protein-coding genes involved in growth factor receptor signalling, cell cycle and apoptosis entry, we complemented this analysis with a literature search to focus on nine pairs of genetic alterations of our dataset, with subsequent verification in three other datasets available publically. To understand the reasons and contexts of these patterns of associations while accounting for the dynamics of associated signalling pathways, we built a logical model. This model was validated first on published mutant mice data, then used to study patterns and to draw conclusions on counter-intuitive observations, allowing one to formulate predictions about conditions where combining genetic alterations benefits tumorigenesis. For example, while CDKN2A homozygous deletions occur in a context of FGFR3 activating mutations, our model suggests that additional PIK3CA mutation or p21CIP deletion would greatly favour invasiveness. Further, the model sheds light on the temporal orders of gene alterations, for example, showing how mutual exclusivity of FGFR3 and TP53 mutations is interpretable if FGFR3 is mutated first. Overall, our work shows how to predict combinations of the major gene alterations leading to invasiveness.
Robotic Systems, 1992
Current techniques for autonomous mobile robots control fall into two main classes: the hierarchi... more Current techniques for autonomous mobile robots control fall into two main classes: the hierarchical approach [2] and the blackboard approach.[8]. In the first, a vertical decomposition of the robot programming problem is carried out. Each layer of control gives the robot new abilities relying upon abilities it already possesses [2]. The second is based on a horizontal decomposition which is more functional than the previous approach. A Blackboard structure allows cooperation between all the subsystems, considered as ...
Lecture Notes in Computer Science, 2006
Abstract. Logical modelling and Petri nets constitute two complemen-tary approaches for the dynam... more Abstract. Logical modelling and Petri nets constitute two complemen-tary approaches for the dynamical modelling of biological regulatory net-works. Leaning on a translation of logical models into standard Petri nets, we propose a formalisation of the notion of circuit functionality in ...
Lecture Notes in Computer Science, 2004
In this paper, a systematic rewriting of logical genetic regulatory graphs in terms of standard P... more In this paper, a systematic rewriting of logical genetic regulatory graphs in terms of standard Petri net models is proposed. We show that, in the Boolean case, the combination of the logical approach with the standard Petri net framework enables the analysis of isolated regulatory circuits, confirming their most fundamental dynamical properties. Furthermore, two more realistic applications are also presented,
these authors contributed equally to this work.
Bioinformatics of Genome Regulation and Structure II, 2006
We present a qualitative approach to gene network modelling, together with a computational implem... more We present a qualitative approach to gene network modelling, together with a computational implementation (GINsim software). Applied to the Drosophila segmentation network, our logical analysis leads to the delineation of the crucial interactions and regulatory circuits involved in the main differentiation decisions at the basis of the segmentation process. The resulting logical models can be further used to perform in
Lecture Notes in Computer Science, 2006
The complexity of biological regulatory networks calls for the development of proper mathematical... more The complexity of biological regulatory networks calls for the development of proper mathematical methods to model their struc- tures and to give insight in their dynamical behaviours. One qualitative approach consists in modelling regulatory networks in terms of logical equations (using either Boolean or multi-level discretisation). Petri Nets (PNs) offer a complementary framework to analyse large systems. In this paper,
Computational modeling constitutes a crucial step toward the functional understanding of complex ... more Computational modeling constitutes a crucial step toward the functional understanding of complex cellular networks. In particular, logical modeling has proven suitable for the dynamical analysis of large signaling and transcriptional regulatory networks. In this context, signaling input components are generally meant to convey external stimuli, or environmental cues. In response to such external signals, cells acquire specific gene expression patterns modeled in terms of attractors (e.g., stable states).The capacity for cells to alter or reprogram their differentiated states upon changes in environmental conditions is referred to as cell plasticity. In this article, we present a multivalued logical framework along with computational methods recently developed to efficiently analyze large models. We mainly focus on a symbolic model checking approach to investigate switches between attractors subsequent to changes of input conditions. As a case study, we consider the cellular network regulating the differentiation of T-helper (Th) cells, which orchestrate many physiological and pathological immune responses. To account for novel cellular subtypes, we present an extended version of a published model of Th cell differentiation. We then use symbolic model checking to analyze reachability properties between Th subtypes upon changes of environmental cues. This allows for the construction of a synthetic view of Th cell plasticity in terms of a graph connecting subtypes with arcs labeled by input conditions. Finally, we explore novel strategies enabling specificTh cell polarizing or reprograming events.
Building upon the logical approach developed by the group of R. Thomas in Brussels, we are defini... more Building upon the logical approach developed by the group of R. Thomas in Brussels, we are defining a rigorous mathematical framework to model genetic regulatory graphs. Referring to discrete mathematics and graph-theoretic notions, our formal approach supports the development of a software suite in Java, GIN-sim, which allows the qualitative simulation and the analysis of the dynamics of regulatory graphs,
Proceedings - 9th International Workshop on Discrete Event Systems, WODES' 08, 2008
Regulatory networks are at the core of the control of cellular processes, integrating varied mole... more Regulatory networks are at the core of the control of cellular processes, integrating varied molecular components connected through diverse relations. Because of the high complexity of these networks, there is a real need for dedicated modelling and analysis tools, to better understand how observed cellular behaviours are governed. Beyond a better understanding, dynamical modelling should also support hypothesis validation and
Advances in Intelligent and Soft Computing, 2011
... Beatriz Luna · Claudine Chaouiya IGC, Rua da Quinta Grande 6 P-2780-156 Oeiras Portugal e-mai... more ... Beatriz Luna · Claudine Chaouiya IGC, Rua da Quinta Grande 6 P-2780-156 Oeiras Portugal e-mail: {boliveira,chaouiya}@igc.gulbenkian.pt ... To avoid cumbersome notations, we assume here that there are no multiple arcs in the regulatory graph (ie no regulators having distinct ...
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 2012
ABSTRACT
Computational Methods in Systems Biology, 2007
The complexity of biological regulatory networks calls for the development of proper mathematical... more The complexity of biological regulatory networks calls for the development of proper mathematical methods to model their structures and to obtain insight in their dynamical behaviours. One qualitative approach consists in modelling regulatory networks in terms of logical equations (using either Boolean or multi-valued discretisation). In this paper, we propose a novel implementation of the generalised logical formalism by means
Computational Methods in Systems Biology, 2009
To cope with the increasing complexity of regulatory networks, we define a reduction method for m... more To cope with the increasing complexity of regulatory networks, we define a reduction method for multi-valued logical models. Starting with a detailed model, this method enables the computation of a reduced model by iteratively “hiding” regulatory components. To keep a consistent behaviour, the logical rules associated with the targets of each hidden node are actualised to account for the (indirect)
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Papers by Claudine Chaouiya