Mostrando recursos 1 - 13 de 13

  1. Majority rules with random tie-breaking in Boolean gene regulatory networks

    Chaouiya, Claudine; Ourrad, Ouerdia; Lima, Ricardo
    We consider threshold boolean gene regulatory networks, where the update function of each gene is described as a majority rule evaluated among the regulators of that gene: it is turned ON when the sum of its regulator contributions is positive (activators contribute positively whereas repressors contribute negatively) and turned OFF when this sum is negative. In case of a tie (when contributions cancel each other out), it is often assumed that the gene keeps it current state. This framework has been successfully used to model cell cycle control in yeast. Moreover, several studies consider stochastic extensions to assess the robustness...

  2. SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools

    Chaouiya, Claudine; Bérenguier, Duncan; Keating, Sarah M; Naldi, Aurélien; van Iersel, Martijn P; Rodriguez, Nicolas; Dräger, Andreas; Büchel, Finja; Cokelaer, Thomas; Kowal, Bryan; Wicks, Benjamin; Gonçalves, Emanuel; Dorier, Julien; Page, Michel; Monteiro, Pedro T; von Kamp, Axel; Xenarios, Ioannis; de Jong, Hidde; Hucka, Michael; Klamt, Steffen; Thieffry, Denis; Le Novère, Nicolas; Saez-Rodriguez, Julio; Helikar, Tomáš
    Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing.

  3. Bringing Dicynodonts Back to Life: Paleobiology and Anatomy of a New Emydopoid Genus from the Upper Permian of Mozambique

    Castanhinha, Rui; Araújo, Ricardo; Júnior, Luís C.; Angielczyk, Kenneth D.; Martins, Gabriel G.; Martins, Rui M. S.; Chaouiya, Claudine; Beckmann, Felix; Wilde, Fabian
    Dicynodontia represent the most diverse tetrapod group during the Late Permian. They survived the Permo-Triassic extinction and are central to understanding Permo-Triassic terrestrial ecosystems. Although extensively studied, several aspects of dicynodont paleobiology such as, neuroanatomy, inner ear morphology and internal cranial anatomy remain obscure. Here we describe a new dicynodont (Therapsida, Anomodontia) from northern Mozambique: Niassodon mfumukasi gen. et sp. nov. The holotype ML1620 was collected from the Late Permian K5 formation, Metangula Graben, Niassa Province northern Mozambique, an almost completely unexplored basin and country for vertebrate paleontology. Synchrotron radiation based micro-computed tomography (SRµCT), combined with a phylogenetic analysis, demonstrates...

  4. Path2Models: large-scale generation of computational models from biochemical pathway maps

    Büchel, Finja; Rodriguez, Nicolas; Swainston, Neil; Wrzodek, Clemens; Czauderna, Tobias; Keller, Roland; Mittag, Florian; Schubert, Michael; Glont, Mihai; Golebiewski, Martin; van Iersel, Martijn; Keating, Sarah; Rall, Matthias; Wybrow, Michael; Hermjakob, Henning; Hucka, Michael; Kell, Douglas B; Müller, Wolfgang; Mendes, Pedro; Zell, Andreas; Chaouiya, Claudine; Saez-Rodriguez, Julio; Schreiber, Falk; Laibe, Camille; Dräger, Andreas; Le Novère, Nicolas
    Systems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of pathway data.

  5. Dynamical modeling and analysis of large cellular regulatory networks

    Bérenguier, D.; Chaouiya, C.; Monteiro, P. T.; Naldi, A.; Remy, E.; Thieffry, D.; Tichit, L.
    The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using...

  6. Modelling the onset of senescence at the G1/S cell cycle checkpoint

    Mombach, José CM; Bugs, Cristhian A; Chaouiya, Claudine
    DNA damage (single or double-strand breaks) triggers adapted cellular responses. These responses are elicited through signalling pathways, which activate cell cycle checkpoints and basically lead to three cellular fates: cycle arrest promoting DNA repair, senescence (permanent arrest) or cell death. Cellular senescence is known for having a tumour-suppressive function and its regulation arouses a growing scientific interest. Here, we advance a qualitative model covering DNA damage response pathways, focusing on G1/S checkpoint enforcement, supposedly more sensitive to arrest than G2/M checkpoint.

  7. A Discrete Model of Drosophila Eggshell Patterning Reveals Cell-Autonomous and Juxtacrine Effects

    Fauré, Adrien; Vreede, Barbara M. I.; Sucena, Élio; Chaouiya, Claudine
    The Drosophila eggshell constitutes a remarkable system for the study of epithelial patterning, both experimentally and through computational modeling. Dorsal eggshell appendages arise from specific regions in the anterior follicular epithelium that covers the oocyte: two groups of cells expressing broad (roof cells) bordered by rhomboid expressing cells (floor cells). Despite the large number of genes known to participate in defining these domains and the important modeling efforts put into this developmental system, key patterning events still lack a proper mechanistic understanding and/or genetic basis, and the literature appears to conflict on some crucial points. We tackle these issues with...

  8. Meeting report from the fourth meeting of the Computational Modeling in Biology Network (COMBINE)

    Waltemath, Dagmar; Bergmann, Frank T.; Chaouiya, Claudine; Czauderna, Tobias; Gleeson, Padraig; Goble, Carole; Golebiewski, Martin; Hucka, Michael; Juty, Nick; Krebs, Olga; Le Novère, Nicolas; Mi, Huaiyu; Moraru, Ion I.; Myers, Chris J.; Nickerson, David; Olivier, Brett G.; Rodriguez, Nicolas; Schreiber, Falk; Smith, Lucian; Zhang, Fengkai; Bonnet, Eric
    This report summarizes the topics and activities of the fourth edition of the annual COMBINE meeting, held in Paris during September 16-20 2013,

  9. Logical Modeling and Dynamical Analysis of Cellular Networks

    Abou-Jaoudé, Wassim; Traynard, Pauline; Monteiro, Pedro T.; Saez-Rodriguez, Julio; Helikar, Tomáš; Thieffry, Denis; Chaouiya, Claudine
    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...

  10. Primary sex determination of placental mammals: a modelling study uncovers dynamical developmental constraints in the formation of Sertoli and granulosa cells

    Sánchez, Lucas; Chaouiya, Claudine
    Primary sex determination in placental mammals is a very well studied developmental process. Here, we aim to investigate the currently established scenario and to assess its adequacy to fully recover the observed phenotypes, in the wild type and perturbed situations. Computational modelling allows clarifying network dynamics, elucidating crucial temporal constrains as well as interplay between core regulatory modules.

  11. Primary sex determination of placental mammals: a modelling study uncovers dynamical developmental constraints in the formation of Sertoli and granulosa cells

    Sánchez, Lucas; Chaouiya, Claudine
    Primary sex determination in placental mammals is a very well studied developmental process. Here, we aim to investigate the currently established scenario and to assess its adequacy to fully recover the observed phenotypes, in the wild type and perturbed situations. Computational modelling allows clarifying network dynamics, elucidating crucial temporal constrains as well as interplay between core regulatory modules.

  12. Diversity and plasticity of Th cell types predicted from regulatory network modelling

    Naldi, Aurélien; Carneiro, Jorge; Chaouiya, Claudine; Thieffry, Denis
    Alternative cell differentiation pathways are believed to arise from the concerted action of signalling pathways and transcriptional regulatory networks. However, the prediction of mammalian cell differentiation from the knowledge of the presence of specific signals and transcriptional factors is still a daunting challenge. In this respect, the vertebrate hematopoietic system, with its many branching differentiation pathways and cell types, is a compelling case study. In this paper, we propose an integrated, comprehensive model of the regulatory network and signalling pathways controlling Th cell differentiation. As most available data are qualitative, we rely on a logical formalism to perform extensive dynamical...

  13. Diversity and plasticity of Th cell types predicted from regulatory network modelling

    Naldi, Aurélien; Carneiro, Jorge; Chaouiya, Claudine; Thieffry, Denis
    Alternative cell differentiation pathways are believed to arise from the concerted action of signalling pathways and transcriptional regulatory networks. However, the prediction of mammalian cell differentiation from the knowledge of the presence of specific signals and transcriptional factors is still a daunting challenge. In this respect, the vertebrate hematopoietic system, with its many branching differentiation pathways and cell types, is a compelling case study. In this paper, we propose an integrated, comprehensive model of the regulatory network and signalling pathways controlling Th cell differentiation. As most available data are qualitative, we rely on a logical formalism to perform extensive dynamical...

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