Circuits with broken fibration symmetries perform core logic computations in biological networks

The biological processes of cellular decision making and differentiation involve a plethora of signalling pathways and gene regulatory circuits. These networks, in their turn, exhibit a multitude of motifs playing crucial parts in regulating network activity. Here, we compare the topological placement of motifs in gene regulatory and signalling networks and find that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.

Cellular behavior is governed by gene regulatory processes that are intrinsically dynamic and nonlinear, and are subject to non-negligible amounts of random fluctuations. Such conditions are ubiquitous in physical systems, where they have been studied for decades using the tools of statistical and nonlinear physics. The goal of this review is to show how approaches traditionally used in physics can help in reaching a systems-level understanding of living cells. To that end, w...

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...

The activation/repression of a given gene is typically regulated by multiple transcription factors (TFs) that bind at the gene regulatory region and recruit RNA polymerase (RNAP). The interactions between the promoter region and TFs and between different TFs specify the dynamic responses of the gene under different physiological conditions. By choosing specific regulatory interactions with up to three transcription factors, we designed several functional motifs, each of which...

Central to the functioning of a living cell is its ability to control the readout or expression of information encoded in the genome. In many cases, a single transcription factor protein activates or represses the expression of many genes. As the concentration of the transcription factor varies, the target genes thus undergo correlated changes, and this redundancy limits the ability of the cell to transmit information about input signals. We explore how interactions among the...

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...

Oscillations lie at the core of many biological processes, from the cell cycle, to circadian oscillations and developmental processes. Time-keeping mechanisms are essential to enable organisms to adapt to varying conditions in environmental cycles, from day/night to seasonal. Transcriptional regulatory networks are one of the mechanisms behind these biological oscillations. However, while identifying cyclically expressed genes from time series measurements is relatively easy,...

We present a comparative analysis of large-scale topological and evolutionary properties of transcription networks in three species, the two distant bacteria E. coli and B. subtilis, and the yeast S. cerevisiae. The study focuses on the global aspects of feedback and hierarchy in transcriptional regulatory pathways. While confirming that gene duplication has a significant impact on the shaping of all the analyzed transcription networks, our results point to distinct trends be...

An astonishingly diverse biomolecular circuitry orchestrates the functioning machinery underlying every living cell. These biomolecules and their circuits have been engineered not only for various industrial applications but also to perform other atypical functions that they were not evolved for - including computation. Various kinds of computational challenges, such as solving NP-complete problems with many variables, logical computation, neural network operations, and crypt...

An information processing circuit must be flexible to perform multiple tasks: biochemical information processing circuits in living systems can have multiple functions, requiring them to perform distinct computational tasks in different scenarios. Here, we describe a tunable dynamical system that performs different logical operations (such as AND, OR, and XOR) depending on which basin of attraction the dynamics resides in. We analyze the robustness of these dynamically switch...