scholarly journals Finite-state discrete-time Markov chain models of gene regulatory networks

2014 ◽  
Author(s):  
V.P. Skornyakov ◽  
M.V. Skornyakova ◽  
A.V. Shurygina ◽  
P.V. Skornyakov

AbstractIn this study Markov chain models of gene regulatory networks (GRN) are developed. These models gives the ability to apply the well known theory and tools of Markov chains to GRN analysis. We introduce a new kind of the finite graph of the interactions called the combinatorial net that formally represent a GRN and the transition graphs constructed from interaction graphs. System dynamics are defined as a random walk on the transition graph that is some Markovian chain. A novel concurrent updating scheme (evolution rule) is developed to determine transitions in a transition graph. Our scheme is based on the firing of a random set of non-steady state vertices of a combinatorial net. We demonstrate that this novel scheme gives an advance in the modeling of the asynchronicity. Also we proof the theorem that the combinatorial nets with this updating scheme can asynchronously compute a maximal independent sets of graphs. As proof of concept, we present here a number of simple combinatorial models: a discrete model of auto-repression, a bi-stable switch, the Elowitz repressilator, a self-activation and show that this models exhibit well known properties.

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 220
Author(s):  
Vladimir Skornyakov ◽  
Maria Skornyakova ◽  
Antonina Shurygina ◽  
Pavel Skornyakov

In this study, Markov chain models of gene regulatory networks (GRN) are developed. These models make it possible to apply the well-known theory and tools of Markov chains to GRN analysis. A new kind of finite interaction graph called a combinatorial net is introduced to represent formally a GRN and its transition graphs constructed from interaction graphs. The system dynamics are defined as a random walk on the transition graph, which is a Markov chain. A novel concurrent updating scheme (evolution rule) is developed to determine transitions in a transition graph. The proposed scheme is based on the firing of a random set of non-steady-state vertices in a combinatorial net. It is demonstrated that this novel scheme represents an advance in asynchronicity modeling. The theorem that combinatorial nets with this updating scheme can asynchronously compute a maximal independent set of graphs is also proved. As proof of concept, a number of simple combinatorial models are presented here: a discrete auto-regression model, a bistableswitch, an Elowitz repressilator, and a self-activation model, and it is shown that these models exhibit well-known properties.


Author(s):  
Youfang Cao ◽  
Anna Terebus ◽  
Jie Liang

Stochasticity plays important roles in many biological networks. A fundamental framework for studying the full stochasticity is the Discrete Chemical Master Equation (dCME). Under this framework, the combination of copy numbers of molecular species defines the microstate of the molecular interactions in the network. The probability distribution over these microstates provide a full description of the properties of a stochastic molecular network. However, it is challenging to solve a dCME. In this chapter, we will first discuss how to derive approximation methods including Fokker-Planck equation and the chemical Langevin equation from the dCME. We also discuss the widely used stochastic simulation method. After that, we focus on the direct solutions to the dCME. We first discuss the Finite State Projection (FSP) method, and then introduce the recently developed finite buffer method (fb-dCME) for directly solving both steady state and time-evolving probability landscape of dCME. We show the advantages of the fb-dCME method using two realistic gene regulatory networks.


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