The Logic Backbone of a Transcription Network

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...

We describe the theoretical and computational framework for the Dynamic Signatures for Genetic Regulatory Network (DSGRN) database. The motivation stems from urgent need to understand the global dynamics of biologically relevant signal transduction/gene regulatory networks that have at least 5 to 10 nodes, involve multiple interactions, and decades of parameters. The input to the database computations is a regulatory network, i.e.\ a directed graph with edges indicating up ...

In this work we propose a model for gene expression based on the theory of random dynamical systems (RDS) and show that it has a "modularity property" in the following sense: given any collection of genes that are linked in a transcriptional network, if each of them is individually described by a certain class of RDS then there is a natural, and essentially unique, prescription for coupling them together, respecting the network topology, in such a way that the collective syst...

Knowing which mode of combinatorial regulation (typically, AND or OR logic operation) that a gene employs is important for determining its function in regulatory networks. Here, we introduce a dynamic cross-correlation function between the output of a gene and its upstream regulator concentrations for signatures of combinatorial regulation in gene expression noise. We find that the correlation function is always upwards convex for the AND operation whereas downwards convex fo...

Diverse biological networks exhibit universal features distinguished from those of random networks, calling much attention to their origins and implications. Here we propose a minimal evolution model of Boolean regulatory networks, which evolve by selectively rewiring links towards enhancing adaptability to a changing environment and stability against dynamical perturbations. We find that sparse and heterogeneous connectivity patterns emerge, which show qualitative agreement ...

The last decade has witnessed a surge of theoretical and computational models to describe the dynamics of complex gene regulatory networks, and how these interactions can give rise to multistable and heterogeneous cell populations. As the use of theoretical modeling to describe genetic and biochemical circuits becomes more widespread, theoreticians with mathematical and physical backgrounds routinely apply concepts from statistical physics, non-linear dynamics, and network th...

Gene regulatory networks constitute the first layer of the cellular computation for cell adaptation and surveillance. In these webs, a set of causal relations is built up from thousands of interactions between transcription factors and their target genes. The large size of these webs and their entangled nature make difficult to achieve a global view of their internal organisation. Here, this problem has been addressed through a comparative study for {\em Escherichia coli}, {\...

Boolean networks can be viewed as functions on the set of binary strings of a given length, described via logical rules. They were introduced as dynamic models into biology, in particular as logical models of intracellular regulatory networks involving genes, proteins, and metabolites. Since genes can have several modes of action, depending on their expression levels, binary variables are often not sufficiently rich, requiring the use of multi-valued networks instead. The ste...

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....

Genetic regulatory networks are defined by their topology and by a multitude of continuously adjustable parameters. Here we present a class of simple models within which the relative importance of topology vs. interaction strengths becomes a well-posed problem. We find that complexity - the ability of the network to adopt multiple stable states - is dominated by the adjustable parameters. We comment on the implications for real networks and their evolution.