Abstract

Driven by the desire to understand genomic functions through the interactions among genes and gene products, the research in gene regulatory networks has become a heated area in genomic signal processing. Among the most studied mathematical models are Boolean networks and probabilistic Boolean networks, which are rule-based dynamic systems. This tutorial provides an introduction to the essential concepts of these two Boolean models, and presents the up-to-date analysis and simulation methods developed for them. In the Analysis section, we will show that Boolean models are Markov chains, based on which we present a Markovian steady-state analysis on attractors, and also reveal the relationship between probabilistic Boolean networks and dynamic Bayesian networks (another popular genetic network model), again via Markov analysis; we dedicate the last subsection to structural analysis, which opens a door to other topics such as network control. The Simulation section will start from the basic tasks of creating state transition diagrams and finding attractors, proceed to the simulation of network dynamics and obtaining the steady-state distributions, and finally come to an algorithm of generating artificial Boolean networks with prescribed attractors. The contents are arranged in a roughly logical order, such that the Markov chain analysis lays the basis for the most part of Analysis section, and also prepares the readers to the topics in Simulation section.

Highlights

  • In most living organisms, genome carries the hereditary information that governs their life, death, and reproduction

  • Such study requires the application of signal processing techniques and fast computing algorithms to process the data and interpret the results. These needs in turn have fueled the development of genomic signal processing and the use of mathematical models to describe the complex interactions between genes

  • This tutorial will introduce the basic concepts of Boolean networks and probabilistic Boolean networks, present the mathematical essentials, and discuss some analyses developed for the models and the common simulation issues

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Summary

INTRODUCTION

Genome carries the hereditary information that governs their life, death, and reproduction. The author would like to bring the fundamentals of Boolean models to a wider audience in light of their theoretical value and pragmatic utility This tutorial will introduce the basic concepts of Boolean networks and probabilistic Boolean networks, present the mathematical essentials, and discuss some analyses developed for the models and the common simulation issues. It is written for researchers in the genomic signal processing area, as well as researchers with general mathematics, statistics, engineering, or computer science backgrounds who are interested in this topic. Formal definitions and mathematical foundations will be laid out concisely, with some in-depth mathematical details left to the references

PRELIMINARIES
A Tutorial on Analysis and Simulation
ANALYSES OF BOOLEAN MODELS
Transition Probability Matrix
Boolean Models are Markov Chains
Analytic Method for Computing the Steady-State Probabilities of Attractors
Steady-State Distributions of Attractors in a BN with Perturbations
Steady-State Distributions of Attractors in a PBN
Relationship Between PBNs and Bayesian Networks
An Independent PBN as a Binary-Valued DBN
A Binary-Valued DBN as an Independent PBN
Structural Analysis
Quantitative Measures of the Structure
Structural Perturbation Analysis
SIMULATION ISSUES WITH BOOLEAN MODELS
Generating State Transition Diagram and Finding Attractors
Simulating a Dynamic System
Power Method
M max s
CLOSING WORDS
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