Sequential Reprogramming of Boolean Networks Made Practical

Hugues Mandon (1) , Cui Su (2) , Stefan Haar (1) , Jun Pang (2, 3) , Loïc Paulevé (4)

1 MEXICO - Modeling and Exploitation of Interaction and Concurrency
2 SnT - Interdisciplinary Centre for Security, Reliability and Trust [Luxembourg]
3 FSTC - Faculty of Science, Technology and Communication [Luxembourg]
4 LaBRI - Laboratoire Bordelais de Recherche en Informatique

We address the sequential reprogramming of gene regulatory networks modelled as Boolean networks. We develop an attractor-based sequential reprogramming method to compute all sequential reprogramming paths from a source attractor to a target attractor, where only attractors of the network are used as intermediates. Our method is more practical than existing reprogramming methods as it incorporates several practical constraints: (1) only biologically observable states, viz. attrac-tors, can act as intermediates; (2) certain attractors, such as apoptosis, can be avoided as intermediates; (3) certain nodes can be avoided to perturb as they may be essential for cell survival or difficult to perturb with biomolecular techniques; and (4) given a threshold k, all sequential reprogramming paths with no more than k perturbations are computed. We compare our method with the minimal one-step reprogramming and the minimal sequential reprogramming on a variety of biological networks. The results show that our method can greatly reduces the number of perturbations compared to the one-step reprogramming, while having comparable results with the minimal sequential reprogramming. Moreover , our implementation is scalable for networks of more than 60 nodes.

Mots clés: Attractors; Cell reprogramming; Boolean networks

Domaines: Systèmes et contrôle [cs.SY]; Bio-Informatique, Biologie Systémique [q-bio.QM]

Hugues Mandon, Cui Su, Stefan Haar, Jun Pang, Loïc Paulevé. Sequential Reprogramming of Boolean Networks Made Practical. CMSB 2019 - 17th International Conference on Computational Methods in Systems Biology, Sep 2019, Trieste, France. pp.3--19, ⟨10.1007/978-3-030-31304-3_1⟩. ⟨hal-02178917v2⟩