The large-scale logico-chemical structure of a transcriptional regulation network

Regulatory interactions between genes show a large amount of cross-species variability, even when the underlying functions are conserved: There are many ways to achieve the same function. Here we investigate the ability of regulatory networks to reproduce given expression levels within a simple model of gene regulation. We find an exponentially large space of regulatory networks compatible with a given set of expression levels, giving rise to an extensive entropy of networks....

Interaction graphs provide an important qualitative modeling approach for System Biology. This paper presents a novel approach for construction of interaction graph with the help of Boolean function decomposition. Each decomposition part (Consisting of 2-bits) of the Boolean functions has some important significance. In the dynamics of a biological system, each variable or node is nothing but gene or protein. Their regulation has been explored in terms of interaction graphs w...

Boolean networks have long been used as models of molecular networks and play an increasingly important role in systems biology. This paper describes a software package, Polynome, offered as a web service, that helps users construct Boolean network models based on experimental data and biological input. The key feature is a discrete analog of parameter estimation for continuous models. With only experimental data as input, the software can be used as a tool for reverse-engine...

The significant role of epigenetic mechanisms within natural systems has become increasingly clear. This paper uses a recently presented abstract, tunable Boolean genetic regulatory network model to explore aspects of epigenetics. It is shown how dynamically controlling transcription via a DNA methylation-inspired mechanism can be selected for by simulated evolution under various single and multiple cell scenarios. Further, it is shown that the effects of such control can be ...

Gene regulatory networks (GRNs) are increasingly used for explaining biological processes with complex transcriptional regulation. A GRN links the expression levels of a set of genes via regulatory controls that gene products exert on one another. Boolean networks are a common modeling choice since they balance between detail and ease of analysis. However, even for Boolean networks the problem of fitting a given network model to an expression dataset is NP-Complete. Previous ...

Interacting biological systems at all organizational levels display emergent behavior. Modeling these systems is made challenging by the number and variety of biological components and interactions (from molecules in gene regulatory networks to species in ecological networks) and the often-incomplete state of system knowledge (e.g., the unknown values of kinetic parameters for biochemical reactions). Boolean networks have emerged as a powerful tool for modeling these systems....

We propose a static and a dynamic approach to model biological signaling networks, and show how each can be used to answer relevant biological questions. For this we use the two different mathematical tools of Propositional Logic and Integer Programming. The power of discrete mathematics for handling qualitative as well as quantitative data has so far not been exploited in Molecular Biology, which is mostly driven by experimental research, relying on first-order or statistica...

Methods of modeling cellular regulatory networks as diverse as differential equations and Boolean networks co-exist, however, without any closer correspondence to each other. With the example system of the fission yeast cell cycle control network, we here set the two approaches in relation to each other. We find that the Boolean network can be formulated as a specific coarse-grained limit of the more detailed differential network model for this system. This lays the mathemati...

Modelling gene regulatory networks not only requires a thorough understanding of the biological system depicted but also the ability to accurately represent this system from a mathematical perspective. Throughout this chapter, we aim to familiarise the reader with the biological processes and molecular factors at play in the process of gene expression regulation.We first describe the different interactions controlling each step of the expression process, from transcription to...

High-throughput experiments are shedding light on the topology of large regulatory networks and at the same time their functional states, namely the states of activation of the nodes (for example transcript or protein levels) in different conditions, times, environments. We now possess a certain amount of information about these two levels of description, stored in libraries, databases and ontologies. A current challenge is to bridge the gap between topology and function, i.e...