Dimension Reduction of Large AND-NOT Network Models

Boolean networks have been used successfully in modeling biological networks and provide a good framework for theoretical analysis. However, the analysis of large networks is not trivial. In order to simplify the analysis of such networks, several model reduction algorithms have been proposed; however, it is not clear if such algorithms scale well with respect to the number of nodes. The goal of this paper is to propose and implement an algorithm for the reduction of AND-NOT network models for the purpose of steady state computation. Our method of network reduction is the use of "steady state approximations" that do not change the number of steady states. Our algorithm is designed to work at the wiring diagram level without the need to evaluate or simplify Boolean functions. Also, our implementation of the algorithm takes advantage of the sparsity typical of discrete models of biological systems. The main features of our algorithm are that it works at the wiring diagram level, it runs in polynomial time, and it preserves the number of steady states. We used our results to study AND-NOT network models of gene networks and showed that our algorithm greatly simplifies steady state analysis. Furthermore, our algorithm can handle sparse AND-NOT networks with up to 1000000 nodes

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

A matrix perturbation method for computing the steady-state probability distributions of probabilistic Boolean networks with gene perturbations

Modeling genetic regulatory interactions is an important issue in systems biology. Probabilistic Boolean networks (PBNs) have been proved to be a useful tool for the task. The steady-state probability distribution of a PBN gives important information about the captured genetic network. The computation of the steady-state probability distribution involves the construction of the transition probability matrix of the PBN. The size of the transition probability matrix is 2n×2n where n is the number of genes. Although given the number of genes and the perturbation probability in a perturbed PBN, the perturbation matrix is the same for different PBNs, the storage requirement for this matrix is huge if the number of genes is large. Thus an important issue is developing computational methods from the perturbation point of view. In this paper, we analyze and estimate the steady-state probability distribution of a PBN with gene perturbations. We first analyze the perturbation matrix. We then give a perturbation matrix analysis for the captured PBN problem and propose a method for computing the steady-state probability distribution. An approximation method with error analysis is then given for further reducing the computational complexity. Numerical experiments are given to demonstrate the efficiency of the proposed methods. © 2010 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex