Abstract

Boolean network (BN) is a simple model widely used to study complex dynamic behaviour of biological systems. Nonetheless, it might be difficult to gather enough data to precisely capture the behavior of a biological system into a set of Boolean functions. These issues can be dealt with to some extent using parametrised Boolean networks (ParBNs), as this model allows leaving some update functions unspecified. In our work, we attack the control problem for ParBNs with asynchronous semantics. While there is an extensive work on controlling BNs without parameters, the problem of control for ParBNs has not been in fact addressed yet. The goal of control is to ensure the stabilisation of a system in a given state using as few interventions as possible. There are many ways to control BN dynamics. Here, we consider the one-step approach in which the system is instantaneously perturbed out of its actual state. A naïve approach to handle control of ParBNs is using parameter scan and solve the control problem for each parameter valuation separately using known techniques for non-parametrised BNs. This approach is however highly inefficient as the parameter space of ParBNs grows doubly exponentially in the worst case. We propose a novel semi-symbolic algorithm for the one-step control problem of ParBNs, that builds on symbolic data structures to avoid scanning individual parameters. We evaluate the performance of our approach on real biological models.

Highlights

  • Cell reprogramming is currently one of the most critical challenges in computational biology

  • We propose an efficient alternative to the naïve parameter scan approach to compute the one-step target control of parametrised Boolean networks (ParBNs)

  • We introduced the control problem for parametrised Boolean networks and we proposed an algorithm for solving the source-target variant of this problem using one-step perturbations

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Summary

Introduction

Cell reprogramming is currently one of the most critical challenges in computational biology. The goal of cell reprogramming is to control the cell’s phenotype. This ability opens many opportunities, mainly in regenerative medicine. That is close to impossible to achieve using only in vitro biological experiments due to the very high number of possibilities of how the cell might be interfered with. This is where in silico analysis and computational models of cell dynamics come into play. Formal methods and their integration provide a promising technology that allows fully automatic identification of control strategies by using computational models

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