The Logic Backbone of a Transcription Network

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...

Interaction graphs provide an important qualitative modeling approach for System Biology. This paper presents a novel approach for construction of interaction graph with the help of Boolean function decomposition. Each decomposition part (Consisting of 2-bits) of the Boolean functions has some important significance. In the dynamics of a biological system, each variable or node is nothing but gene or protein. Their regulation has been explored in terms of interaction graphs w...

We demonstrate the advantages of feedforward loops using a Boolean network, which is one of the discrete dynamical models for transcriptional regulatory networks. After comparing the dynamical behaviors of network embedded feedback and feedforward loops, we found that feedforward loops can provide higher temporal order (coherence) with lower entropy (randomness) in a temporal program of gene expression. In addition, complexity of the state space that increases with longer len...

The significant role of epigenetic mechanisms within natural systems has become increasingly clear. This paper uses a recently presented abstract, tunable Boolean genetic regulatory network model to explore aspects of epigenetics. It is shown how dynamically controlling transcription via a DNA methylation-inspired mechanism can be selected for by simulated evolution under various single and multiple cell scenarios. Further, it is shown that the effects of such control can be ...

Motivation: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs....

A fundamental task in developmental biology is to identify the mechanisms which drive morphogenesis. In many cases, pattern formation is driven by the positional information determined by both the gradient of maternal factors and hard-wired mechanisms embedded in the genome. Alternative mechanisms of positional information that contribute to patterning are the influence of signals derived from surrounding tissues. In this paper, we show that the interplay of geometrical const...

The complex dynamics of gene expression in living cells can be well-approximated using Boolean networks. The average sensitivity is a natural measure of stability in these systems: values below one indicate typically stable dynamics associated with an ordered phase, whereas values above one indicate chaotic dynamics. This yields a theoretically motivated adaptive advantage to being near the critical value of one, at the boundary between order and chaos. Here, we measure avera...

The determination and classification of fixed points of large Boolean networks is addressed in terms of constraint satisfaction problem. We develop a general simplification scheme that, removing all those variables and functions belonging to trivial logical cascades, returns the computational core of the network. The onset of an easy-to-complex regulatory phase is introduced as a function of the parameters of the model, identifying both theoretically and algorithmically the r...

Gene regulatory networks are powerful abstractions of biological systems. Since the advent of high-throughput measurement technologies in biology in the late 90s, reconstructing the structure of such networks has been a central computational problem in systems biology. While the problem is certainly not solved in its entirety, considerable progress has been made in the last two decades, with mature tools now available. This chapter aims to provide an introduction to the basic...

Biological structure and function depend on complex regulatory interactions between many genes. A wealth of gene expression data is available from high-throughput genome-wide measurement technologies, but effective gene regulatory network inference methods are still needed. Model-based methods founded on quantitative descriptions of gene regulation are among the most promising, but many such methods rely on simple, local models or on ad hoc inference approaches lacking experi...