Skip to Main content Skip to Navigation
Conference papers

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

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.
Complete list of metadata

Cited literature [33 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-02898849
Contributor : Loïc Paulevé <>
Submitted on : Friday, August 21, 2020 - 9:46:48 AM
Last modification on : Saturday, May 1, 2021 - 3:47:05 AM

File

cmsb2020.pdf
Files produced by the author(s)

Identifiers

Citation

Stéphanie Chevalier, Vincent Noël, Laurence Calzone, Andrei Zinovyev, Loïc Paulevé. Synthesis and Simulation of Ensembles of Boolean Networks for Cell Fate Decision. 18th International Conference on Computational Methods in Systems Biology (CMSB), 2020, Online, Germany. pp.193--209, ⟨10.1007/978-3-030-60327-4_11⟩. ⟨hal-02898849v2⟩

Share

Metrics

Record views

204

Files downloads

616