Control of complex networks requires both structure and dynamics

The study of network structure has uncovered signatures of the organization of complex systems. However, there is also a need to understand how to control them; for example, identifying strategies to revert a diseased cell to a healthy state, or a mature cell to a pluripotent state. Two recent methodologies suggest that the controllability of complex systems can be predicted solely from the graph of interactions between variables, without considering their dynamics: structural controllability and minimum dominating sets. We demonstrate that such structure-only methods fail to characterize controllability when dynamics are introduced. We study Boolean network ensembles of network motifs as well as three models of biochemical regulation: the segment polarity network in Drosophila melanogaster, the cell cycle of budding yeast Saccharomyces cerevisiae, and the floral organ arrangement in Arabidopsis thaliana. We demonstrate that structure-only methods both undershoot and overshoot the number and which sets of critical variables best control the dynamics of these models, highlighting the importance of the actual system dynamics in determining control. Our analysis further shows that the logic of automata transition functions, namely how canalizing they are, plays an important role in the extent to which structure predicts dynamics.Comment: 15 pages, 6 figure

Topological and Graph-coloring Conditions on the Parameter-independent Stability of Second-order Networked Systems

In this paper, we study parameter-independent stability in qualitatively heterogeneous passive networked systems containing damped and undamped nodes. Given the graph topology and a set of damped nodes, we ask if output consensus is achieved for all system parameter values. For given parameter values, an eigenspace analysis is used to determine output consensus. The extension to parameter-independent stability is characterized by a coloring problem, named the richly balanced coloring (RBC) problem. The RBC problem asks if all nodes of the graph can be colored red, blue and black in such a way that (i) every damped node is black, (ii) every black node has blue neighbors if and only if it has red neighbors, and (iii) not all nodes in the graph are black. Such a colored graph is referred to as a richly balanced colored graph. Parameter-independent stability is guaranteed if there does not exist a richly balanced coloring. The RBC problem is shown to cover another well-known graph coloring scheme known as zero forcing sets. That is, if the damped nodes form a zero forcing set in the graph, then a richly balanced coloring does not exist and thus, parameter-independent stability is guaranteed. However, the full equivalence of zero forcing sets and parameter-independent stability holds only true for tree graphs. For more general graphs with few fundamental cycles an algorithm, named chord node coloring, is proposed that significantly outperforms a brute-force search for solving the NP-complete RBC problem.Comment: 30 pages, accepted for publication in SICO

Identification of control targets in Boolean molecular network models via computational algebra

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. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. Experimentally, node manipulation requires technology to completely repress or fully activate a particular gene product while edge manipulations only require a drug that inactivates the interaction between two gene products. Results: This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network.Comment: 12 pages, 4 figures, 2 table

Topological and Graph-Coloring Conditions on the Parameter-Independent Stability of Second-Order Networked Systems

In this paper, we study parameter-independent stability in qualitatively heterogeneous passive networked systems containing damped and undamped nodes. Given the graph topology and a set of damped nodes, we ask if output consensus is achieved for all system parameter values. For given parameter values, an eigenspace analysis is used to determine output consensus. The extension to parameter-independent stability is characterized by a coloring problem, named the richly balanced coloring (RBC) problem. The RBC problem asks if all nodes of the graph can be colored red, blue, and black in such a way that (i) every damped node is black, (ii) every black node has blue neighbors if and only if it has red neighbors, and (iii) not all nodes in the graph are black. Such a colored graph is referred to as a richly balanced colored graph. Parameter-independent stability is guaranteed if there does not exist a richly balanced coloring. The RBC problem is shown to cover another well-known graph coloring scheme known as zero forcing sets. That is, if the damped nodes form a zero forcing set in the graph, then a richly balanced coloring does not exist, and thus parameter-independent stability is guaranteed. However, the full equivalence of zero forcing sets and parameter-independent stability holds true only for tree graphs. For more general graphs with few fundamental cycles, an algorithm, named chord node coloring, is proposed that significantly outperforms a brute-force search for solving the NP-complete RBC problem