On the basic computational structure of gene regulatory networks

Networks of gene regulation govern morphogenesis, determine cell identity and regulate cell function. But we have little understanding, at the local level, of which logics are biologically preferred or even permitted. To solve this puzzle, we studied the consequences of a fundamental aspect of gene regulatory networks: genes and transcription factors talk to each other but not themselves. Remarkably, this bipartite structure severely restricts the number of logical dependenci...

The important task of determining the connectivity of gene networks, and at a more detailed level even the kind of interaction existing between genes, can nowadays be tackled by microarraylike technologies. Yet, there is still a large amount of unknowns with respect to the amount of data provided by a single microarray experiment, and therefore reliable gene network retrieval procedures must integrate all of the available biological knowledge, even if coming from different so...

Spatially or chemically isolated functional modules composed of several cellular components and carrying discrete functions are considered fundamental building blocks of cellular organization, but their presence in highly integrated biochemical networks lacks quantitative support. Here we show that the metabolic networks of 43 distinct organisms are organized into many small, highly connected topologic modules that combine in a hierarchical manner into larger, less cohesive u...

The topological analysis of biological networks has been a prolific topic in network science during the last decade. A persistent problem with this approach is the inherent uncertainty and noisy nature of the data. One of the cases in which this situation is more marked is that of transcriptional regulatory networks (TRNs) in bacteria. The datasets are incomplete because regulatory pathways associated to a relevant fraction of bacterial genes remain unknown. Furthermore, dire...

The engineered control of cellular function through the design of synthetic genetic networks is becoming plausible. Here we show how a naturally occurring network can be used as a parts list for artificial network design, and how model formulation leads to computational and analytical approaches relevant to nonlinear dynamics and statistical physics.

Over the past decade, a number of researchers in systems biology have sought to relate the function of biological systems to their network-level descriptions -- lists of the most important players and the pairwise interactions between them. Both for large networks (in which statistical analysis is often framed in terms of the abundance of repeated small subgraphs) and for small networks which can be analyzed in greater detail (or even synthesized in vivo and subjected to expe...

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...

We show that logic computational circuits in gene regulatory networks arise from a fibration symmetry breaking in the network structure. From this idea we implement a constructive procedure that reveals a hierarchy of genetic circuits, ubiquitous across species, that are surprising analogues to the emblematic circuits of solid-state electronics: starting from the transistor and progressing to ring oscillators, current-mirror circuits to toggle switches and flip-flops. These c...

Biological networks are a very convenient modelling and visualisation tool to discover knowledge from modern high-throughput genomics and postgenomics data sets. Indeed, biological entities are not isolated, but are components of complex multi-level systems. We go one step further and advocate for the consideration of causal representations of the interactions in living systems.We present the causal formalism and bring it out in the context of biological networks, when the da...

The cell cycle is a tightly controlled process, yet its underlying genetic network shows marked differences across species. Which of the associated structural features follow solely from the ability to impose the appropriate gene expression patterns? We tackle this question in silico by examining the ensemble of all regulatory networks which satisfy the constraint of producing a given sequence of gene expressions. We focus on three cell cycle profiles coming from baker's yeas...