Motifs emerge from function in model gene regulatory networks

Analysis of the structure of biological networks often uses statistical tests to establish the over-representation of motifs, which are thought to be important building blocks of such networks, related to their biological functions. However, there is disagreement as to the statistical significance of these motifs, and there are potential problems with standard methods for estimating this significance. Exponential random graph models (ERGMs) are a class of statistical model th...

We develop a general method to explore how the function performed by a biological network can constrain both its structural and dynamical network properties. This approach is orthogonal to prior studies which examine the functional consequences of a given structural feature, for example a scale free architecture. A key step is to construct an algorithm that allows us to efficiently sample from a maximum entropy distribution on the space of boolean dynamical networks constrain...

Conventionally, pairwise relationships between nodes are considered to be the fundamental building blocks of complex networks. However, over the last decade the overabundance of certain sub-network patterns, so called motifs, has attracted high attention. It has been hypothesized, these motifs, instead of links, serve as the building blocks of network structures. Although the relation between a network's topology and the general properties of the system, such as its functio...

Topological features of gene regulatory networks can be successfully reproduced by a model population evolving under selection for short dynamical attractors. The evolved population of networks exhibit motif statistics, summarized by significance profiles, which closely match those of {\it E. coli, S. cerevsiae} and {\it B. subtilis}, in such features as the excess of linear motifs and feed-forward loops, and deficiency of feedback loops. The slow relaxation to stasis is a ha...

Network science can offer fundamental insights into the structural and functional properties of complex systems. For example, it is widely known that neuronal circuits tend to organize into basic functional topological modules, called "network motifs". In this article we show that network science tools can be successfully applied also to the study of artificial neural networks operating according to self-organizing (learning) principles. In particular, we study the emergence ...

Interaction networks are of central importance in post-genomic molecular biology, with increasing amounts of data becoming available by high-throughput methods. Examples are gene regulatory networks or protein interaction maps. The main challenge in the analysis of these data is to read off biological functions from the topology of the network. Topological motifs, i.e., patterns occurring repeatedly at different positions in the network have recently been identified as basic ...

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....

Networks are fundamental for our understanding of complex systems. Interactions between individual nodes in networks generate network motifs - small recurrent patterns that can be considered the network's building-block components, providing certain dynamical properties. However, it remains unclear how network motifs are arranged within networks and what properties emerge from interactions between network motifs. Here we develop a framework to explore the mesoscale-level beha...

Network motifs, the recurring regulatory structural patterns in networks, are able to self-organize to produce networks. Three major motifs, feedforward loop, single input modules and bi-fan are found in gene regulatory networks. The large ratio of genes to transcription factors (TFs) in genomes leads to a sharing of TFs by motifs and is sufficient to result in network self-organization. We find a common design principle of these motifs: short transcript's half-life (THL) TFs...

Gene regulatory networks (GRNs) play a central role in cellular decision-making. Understanding their structure and how it impacts their dynamics constitutes thus a fundamental biological question. GRNs are frequently modeled as Boolean networks, which are intuitive, simple to describe, and can yield qualitative results even when data is sparse. We assembled the largest repository of expert-curated Boolean GRN models. A meta-analysis of this diverse set of models reveals sever...