Finding optimal control policy in probabilistic Boolean networks with hard constraints by using integer programming and dynamic programming

Session 2 regularIn this paper, we study control problems of Boolean Networks (BNs) and Probabilistic Boolean Networks (PBNs). For BN CONTROL, by applying external control, we propose to derive the network to the desired state within a few time steps. For PBN CONTROL, we propose to find a control sequence such that the network will terminate in the desired state with a maximum probability. Also, we propose to minimize the maximum cost of the terminal state to which the network will enter. Integer linear programming and dynamic programming in conjunction with hard constraints are then employed to solve the above problems. Numerical experiments are given to demonstrate the effectiveness of our algorithms.We also present a hardness result suggesting that PBN CONTROL is harder than BN CONTROL. ©2010 IEEE.published_or_final_versio

Finding optimal control policy by using dynamic programming in conjunction with state reduction

In this paper we study the problem of finding optimal control policy for probabilistic Boolean networks (PBNs). Previous works have been done by using dynamic programming-based (DP) method. However, due to the high computational complexity of PBNs, DP method is computationally inefficient for large networks. Inspired by the state reduction strategies studied in [10], we consider using dynamic programming in conjunction with state reduction approach to reduce the computational cost of DP method. Numerical examples are given to demonstrate the efficiency of our proposed method. © 2011 IEEE.published_or_final_versionThe 2011 IEEE International Conference on Systems Biology (ISB), Zhuhai, China, 2-4 September 2011. In Proceedings of ISB, 2011, p. 274-27

On optimal control policy for Probabilistic Boolean Network: a state reduction approach

BACKGROUND: Probabilistic Boolean Network (PBN) is a popular model for studying genetic regulatory networks. An important and practical problem is to find the optimal control policy for a PBN so as to avoid the network from entering into undesirable states. A number of research works have been done by using dynamic programming-based (DP) method. However, due to the high computational complexity of PBNs, DP method is computationally inefficient for a large size network. Therefore it is natural to seek for approximation methods. RESULTS: Inspired by the state reduction strategies, we consider using dynamic programming in conjunction with state reduction approach to reduce the computational cost of the DP method. Numerical examples are given to demonstrate both the effectiveness and the efficiency of our proposed method. CONCLUSIONS: Finding the optimal control policy for PBNs is meaningful. The proposed problem has been shown to be ∑ p 2 - hard . By taking state reduction approach into consideration, the proposed method can speed up the computational time in applying dynamic programming-based algorithm. In particular, the proposed method is effective for larger size networks.published_or_final_versio

On control of singleton attractors in multiple Boolean networks: integer programming-based method

published_or_final_versionThe Twelfth Asia Pacific Bioinformatics Conference (APBC 2014), Shanghai, China. 17-19 January 2014. In BMC Systems Biology, 2014, v. 8, Suppl. 1, article no. S

Therapeutic target discovery using Boolean network attractors: avoiding pathological phenotypes

Target identification, one of the steps of drug discovery, aims at identifying biomolecules whose function should be therapeutically altered in order to cure the considered pathology. This work proposes an algorithm for in silico target identification using Boolean network attractors. It assumes that attractors of dynamical systems, such as Boolean networks, correspond to phenotypes produced by the modeled biological system. Under this assumption, and given a Boolean network modeling a pathophysiology, the algorithm identifies target combinations able to remove attractors associated with pathological phenotypes. It is tested on a Boolean model of the mammalian cell cycle bearing a constitutive inactivation of the retinoblastoma protein, as seen in cancers, and its applications are illustrated on a Boolean model of Fanconi anemia. The results show that the algorithm returns target combinations able to remove attractors associated with pathological phenotypes and then succeeds in performing the proposed in silico target identification. However, as with any in silico evidence, there is a bridge to cross between theory and practice, thus requiring it to be used in combination with wet lab experiments. Nevertheless, it is expected that the algorithm is of interest for target identification, notably by exploiting the inexpensiveness and predictive power of computational approaches to optimize the efficiency of costly wet lab experiments.Comment: Since the publication of this article and among the possible improvements mentioned in the Conclusion, two improvements have been done: extending the algorithm for multivalued logic and considering the basins of attraction of the pathological attractors for selecting the therapeutic bullet

Finding optimal control policy in probabilistic Boolean Networks with hard constraints by using integer programming and dynamic programming

Boolean Networks (BNs) and Probabilistic Boolean Networks (PBNs) are studied in this paper from the viewpoint of control problems. For BN CONTROL, by applying external control, we propose to derive the network to the desired state within a few time steps. For PBN CONTROL, we propose to find a control sequence such that the network will terminate in the desired state with a maximum probability. Also, we propose to minimise the maximum cost of the terminal state to which the network will enter. We also present a hardness result suggesting that PBN CONTROL is harder than BN CONTROL