Quantitative analysis of robustness and fragility in biological networks based on feedback dynamics

@article{Kwon2008QuantitativeAO,
  title={Quantitative analysis of robustness and fragility in biological networks based on feedback dynamics},
  author={Yung-Keun Kwon and Kwang-Hyun Cho},
  journal={Bioinformatics},
  year={2008},
  volume={24 7},
  pages={
          987-94
        }
}
MOTIVATION It has been widely reported that biological networks are robust against perturbations such as mutations. On the contrary, it has also been known that biological networks are often fragile against unexpected mutations. There is a growing interest in these intriguing observations and the underlying design principle that causes such robust but fragile characteristics of biological networks. For relatively small networks, a feedback loop has been considered as an important motif for… 

Figures from this paper

Interplay of Positive and Negative Feedback loops Governs Robustness in Multistable Biological Networks

This work investigated dynamic and structural robustness in biological networks with regards to phenotypic distribution and plasticity and identified a metric that can explain the structural and dynamical robustness of these networks.

Structurally robust biological networks

The impact of the results is to highlight that classical and simple control theory methods are extremely useful to characterize the behavior of biological networks analytically, and demonstrate that some biological networks are robust thanks to their structure and some qualitative properties of the interactions, regardless of the specific values of their parameters.

A coherent feedforward loop design principle to sustain robustness of biological networks

It is found that coherent FFLs increase robustness because these structures induce downstream nodes to be robust against update-rule perturbations, and can be considered as a design principle of human signaling networks that improve network robustness against update.

Coherent coupling of feedback loops: a design principle of cell signaling networks

The robustness achieved by coherently coupled feedback loops can be kept evolutionarily stable and imply that the coherent coupling of feedback loops might be a design principle of cell signaling networks devised to achieve the robustness.

The role of feedback mechanisms in biological network models—A tutorial

The role of feedback mechanisms for intracellular regulation processes on different biological examples are discussed and recent attempts to develop a comprehensive theory that is also applicable for more complex networks of interrelated feedback structures are discussed.

Robustness and Evolvability of the Human Signaling Network

The results show that the human signaling network can be divided into an evolvable core where perturbations change the attractor landscape in state space, and a robust neighbor where perturations have no effect on the attractingor landscape.

The relationship between modularity and robustness in signalling networks

It is observed that the network robustness is negatively correlated with the network modularity, and this correlation becomes more apparent as the network density becomes sparser, which implies that dynamically similar nodes tend to be located in the same module of a network.

Properties of Boolean dynamics by node classification using feedback loops in a network

It is proved that every NFU node is eventually frozen in Boolean dynamics, and it is shown that genes with a high perturbation-sustainable probability are likely to be essential, disease, and drug-target genes in large human signaling networks.

Fragile robustness: principles and practice

This work describes a quantitative method for defining the fragility and robustness of system fluxes and metabolite concentrations to perturbations in enzyme activity, and extends the definition of robustness, defining robustness coefficients forcellular properties other than flux or metabolite concentration, and to perturbedations other than changes in enzymes activity.

Investigation on changes of modularity and robustness by edge-removal mutations in signaling networks

The analysis of changes of robustness and modularity against edge-removal mutations can be useful to unravel novel dynamical characteristics underlying in signaling networks.
...

References

SHOWING 1-10 OF 40 REFERENCES

Boolean dynamics of biological networks with multiple coupled feedback loops.

This article investigates the relationship between the multiple coupled feedback loops and the dynamics of Boolean networks and shows that networks have a larger proportion of basins corresponding to fixed-point attractors as they have more coupled negative feedback loops.

Robustness Can Evolve Gradually in Complex Regulatory Gene Networks with Varying Topology

A model of transcriptional regulation networks, in which millions of different network topologies are explored, shows that connectedness and evolvability of robust networks may be a general organizational principle of biological networks.

Dynamic Properties of Network Motifs Contribute to Biological Network Organization

It is proposed that robust dynamical stability is an influential property that can determine the non-random structure of biological networks.

Robustness as a measure of plausibility in models of biochemical networks.

The hypothesis that potential errors in models will result in parameter sensitivities is tested by analysis of two models of the biochemical oscillator underlying the Xenopus cell cycle and the analysis successfully identifies known weaknesses in the older model and suggests areas for further investigation in the more recent model.

Coupled feedback loops form dynamic motifs of cellular networks.

It is discovered that coupled positive feedbacks enhance signal amplification and bistable characteristics; coupled negative feedbacks realize enhanced homeostasis; coupled positive andnegative feedbacks enable reliable decision-making by properly modulating signal responses and effectively dealing with noise.

Topology and Robustness in the Drosophila Segment Polarity Network

It is shown that bistability is necessary to form the segment polarity pattern and serves as a strong predictor of which parameter sets will succeed in forming the pattern and how large changes in parameters can change the specific pattern produced by a network.

Biological robustness

Insights into inherent properties of robust systems will provide a better understanding of complex diseases and a guiding principle for therapy design.

Robustness and fragility of Boolean models for genetic regulatory networks.

Robustness of a gene regulatory circuit

This work concludes that the behavior of the phage λ gene regulatory circuitry is highly robust, and proposes a two‐step pathway, in which robustness plays a key role, for evolution of complex regulatory circuitry.