Relative Stability of Network States in Boolean Network Models of Gene Regulation in Development

Progress in cell type reprogramming has revived the interest in Waddington's concept of the epigenetic landscape. Recently researchers developed the quasi-potential theory to represent the Waddington's landscape. The Quasi-potential U(x), derived from interactions in the gene regulatory network (GRN) of a cell, quantifies the relative stability of network states, which determine the effort required for state transitions in a multi-stable dynamical system. However, quasi-potential landscapes, originally developed for continuous systems, are not suitable for discrete-valued networks which are important tools to study complex systems. In this paper, we provide a framework to quantify the landscape for discrete Boolean networks (BNs). We apply our framework to study pancreas cell differentiation where an ensemble of BN models is considered based on the structure of a minimal GRN for pancreas development. We impose biologically motivated structural constraints (corresponding to specific type of Boolean functions) and dynamical constraints (corresponding to stable attractor states) to limit the space of BN models for pancreas development. In addition, we enforce a novel functional constraint corresponding to the relative ordering of attractor states in BN models to restrict the space of BN models to the biological relevant class. We find that BNs with canalyzing/sign-compatible Boolean functions best capture the dynamics of pancreas cell differentiation. This framework can also determine the genes' influence on cell state transitions, and thus can facilitate the rational design of cell reprogramming protocols.Comment: 24 pages, 6 figures, 1 tabl

Global synchronization for discrete-time stochastic complex networks with randomly occurred nonlinearities and mixed time delays

Copyright [2010] IEEE. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of Brunel University's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to [email protected]. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.In this paper, the problem of stochastic synchronization analysis is investigated for a new array of coupled discrete-time stochastic complex networks with randomly occurred nonlinearities (RONs) and time delays. The discrete-time complex networks under consideration are subject to: (1) stochastic nonlinearities that occur according to the Bernoulli distributed white noise sequences; (2) stochastic disturbances that enter the coupling term, the delayed coupling term as well as the overall network; and (3) time delays that include both the discrete and distributed ones. Note that the newly introduced RONs and the multiple stochastic disturbances can better reflect the dynamical behaviors of coupled complex networks whose information transmission process is affected by a noisy environment (e.g., Internet-based control systems). By constructing a novel Lyapunov-like matrix functional, the idea of delay fractioning is applied to deal with the addressed synchronization analysis problem. By employing a combination of the linear matrix inequality (LMI) techniques, the free-weighting matrix method and stochastic analysis theories, several delay-dependent sufficient conditions are obtained which ensure the asymptotic synchronization in the mean square sense for the discrete-time stochastic complex networks with time delays. The criteria derived are characterized in terms of LMIs whose solution can be solved by utilizing the standard numerical software. A simulation example is presented to show the effectiveness and applicability of the proposed results

A Monte Carlo Approach to Measure the Robustness of Boolean Networks

Emergence of robustness in biological networks is a paramount feature of evolving organisms, but a study of this property in vivo, for any level of representation such as Genetic, Metabolic, or Neuronal Networks, is a very hard challenge. In the case of Genetic Networks, mathematical models have been used in this context to provide insights on their robustness, but even in relatively simple formulations, such as Boolean Networks (BN), it might not be feasible to compute some measures for large system sizes. We describe in this work a Monte Carlo approach to calculate the size of the largest basin of attraction of a BN, which is intrinsically associated with its robustness, that can be used regardless the network size. We show the stability of our method through finite-size analysis and validate it with a full search on small networks.Comment: on 1st International Workshop on Robustness and Stability of Biological Systems and Computational Solutions (WRSBS