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Synthesis and Simulation of Ensembles of Boolean Networks for Cell Fate Decision

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Computational Methods in Systems Biology (CMSB 2020)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 12314))

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Abstract

The construction of models of biological networks from prior knowledge and experimental data often leads to a multitude of candidate models. Devising a single model from them can require arbitrary choices, which may lead to strong biases in subsequent predictions.

We introduce here a methodology for a) synthesizing Boolean model ensembles satisfying a set of biologically relevant constraints and b) reasoning on the dynamics of the ensembles of models. The synthesis is performed using Answer-Set Programming, extending prior work to account for solution diversity and universal constraints on reachable fixed points, enabling an accurate specification of desired dynamics. The sampled models are then simulated and the results are aggregated through averaging or can be analyzed as a multi-dimensional distribution.

We illustrate our approach on a previously published Boolean model of a molecular network regulating the cell fate decisions in cancer progression. It appears that the ensemble-based approach to Boolean modelling brings new insights on the variability of synergistic interacting mutations effect concerning propensity of a cancer cell to metastasize.

S. Chevalier and V. Noël—Co-first authors.

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Notes

  1. 1.

    https://maboss.curie.fr, https://github.com/colomoto/pyMaBoSS.

  2. 2.

    Code, data, and notebooks at https://doi.org/10.5281/zenodo.3938904; Synthesis has been performed on 36-cores CPUs @ 2.6 Ghz with 192 Go of RAM; first ensemble was generated at a rate of 5 s/model/CPU; second ensemble was generated at a rate of 3 min/model/CPU.

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Acknowledgements

This work has been partially supported by Agence Nationale de la Recherche in the program Investissements d’Avenir (project No. ANR-19-P3IA-0001; PRAIRIE 3IA Institute), by ANR-FNR project “AlgoReCell” (ANR-16-CE12-0034), by ITMO Cancer, and by the Ministry of Science and Higher Education of the Russian Federation (project No. 14.Y26.31.0022). Experiments were carried out using the PlaFRIM experimental testbed,supported by Inria, CNRS (LABRI and IMB), Université de Bordeaux, Bordeaux INP and Conseil Régionald’Aquitaine (see https://www.plafrim.fr).

Author information

Authors and Affiliations

  1. LRI, CNRS, UMR8623, Univ. Paris-Saclay, Orsay, France

    Stéphanie Chevalier

  2. Institut Curie, INSERM, U. PSL, Mines ParisTech, Paris, France

    Vincent Noël, Laurence Calzone & Andrei Zinovyev

  3. Lobachevsky University, 603000, Nizhny Novgorod, Russia

    Andrei Zinovyev

  4. Univ. Bordeaux, Bordeaux INP, CNRS, LaBRI, UMR5800, 33400, Talence, France

    Loïc Paulevé

Authors
  1. Stéphanie Chevalier
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  2. Vincent Noël
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  3. Laurence Calzone
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  4. Andrei Zinovyev
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  5. Loïc Paulevé
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Correspondence to Loïc Paulevé .

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Editors and Affiliations

  1. Department of Computer Science, University of Oxford, Oxford, UK

    Alessandro Abate

  2. Department of Computer and Information Science, University of Konstanz, Konstanz, Germany

    Tatjana Petrov

  3. Department of Computer Science, Saarland University, Saarbrücken, Germany

    Verena Wolf

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Chevalier, S., Noël, V., Calzone, L., Zinovyev, A., Paulevé, L. (2020). Synthesis and Simulation of Ensembles of Boolean Networks for Cell Fate Decision. In: Abate, A., Petrov, T., Wolf, V. (eds) Computational Methods in Systems Biology. CMSB 2020. Lecture Notes in Computer Science(), vol 12314. Springer, Cham. https://doi.org/10.1007/978-3-030-60327-4_11

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  • DOI: https://doi.org/10.1007/978-3-030-60327-4_11

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  • Print ISBN: 978-3-030-60326-7

  • Online ISBN: 978-3-030-60327-4

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