Gene regulatory and signalling networks exhibit distinct topological distributions of motifs

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 ...

Developing and maintaining life requires a lot of computation. This is done by gene regulatory networks. But we have little understanding of how this computation is organized. I show that there is a direct correspondence between the structural and functional building blocks of regulatory networks, which I call regulatory motifs. I derive a simple bound on the range of function that these motifs can perform, in terms of the local network structure. I prove that this range is a...

Topological network motifs represent functional relationships within and between regulatory and protein-protein interaction networks. Enriched motifs often aggregate into self-contained units forming functional modules. Theoretical models for network evolution by duplication-divergence mechanisms and for network topology by hierarchical scale-free networks have suggested a one-to-one relation between network motif enrichment and aggregation, but this relation has never been t...

Gene duplication is a fundamental evolutionary mechanism that contributes to biological complexity and diversity (Fortna et al., 2004). Traditionally, research has focused on the duplication of gene sequences (Zhang, 1914). However, evidence suggests that the duplication of regulatory elements may also play a significant role in the evolution of genomic functions (Teichmann and Babu, 2004; Hallin and Landry, 2019). In this work, the evolution of regulatory relationships belon...

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...

Background: Networks in different domains are characterized by similar global characteristics while differing in local structures. To further extend this concept, we investigated network regularities on a fine scale in order to examine the functional impact of recurring motifs in signed oriented biological networks. In this work we generalize to signaling net works some considerations made on feedback and feed forward loops and extend them by adding a close scrutiny of Linear...

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 arise in all living cells, allowing the control of gene expression patterns. The study of their topology has revealed that certain subgraphs of interactions or "motifs" appear at anomalously high frequencies. We ask here whether this phenomenon may emerge because of the functions carried out by these networks. Given a framework for describing regulatory interactions and dynamics, we consider in the space of all regulatory networks those that have a pr...

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...

Motif discovery is a powerful approach to understanding network structures and their function. We present a comprehensive analysis of regulatory motifs in the connectome of the model organism Caenorhabditis elegans (C. elegans). Leveraging the Efficient Subgraph Counting Algorithmic PackagE (ESCAPE) algorithm, we identify network motifs in the multi-layer nervous system of C. elegans and link them to functional circuits. We further investigate motif enrichment within signal p...