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

Abstract

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.