Defining Network Topologies that Can Achieve Biochemical Adaptation

By Wenzhe Ma, A. Trusina, H. El-Samad, Wendell A. Lim, Chao Tang. Cell, 2009

970 citations recorded by the source corpus.

Many signaling systems show adaptation — the ability to reset themselves after responding to a stimulus. We computationally searched all possible three‐node enzyme network topologies to identify those that could perform adaptation. Only two major core topologies emerge as robust solutions: a negative feedback loop with a buffering node and an incoherent feedforward loop with a proportioner node. Minimal circuits containing these topologies are, within proper regions of parameter space, sufficient to achieve adaptation. More complex circuits that robustly perform adaptation all contain at least one of these topologies at their core. This analysis yields a design table highlighting a finite set of adaptive circuits. Despite the diversity of possible biochemical networks, it may be common to find that only a finite set of core topologies can execute a particular function. These design rules provide a framework for functionally classifying complex natural networks and a manual for engineering networks.

Subfields: Biophysics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f7667b99e8a1d7cfab2a4c3feffe03f15a34d2ed

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Citations in the corpus

Principles of assembly reveal a periodic table of protein complexes (2015, methodology): “The periodic table illustrates both the variety of observed protein complexes and the space of possible topologies through exhaustive enumeration, analogous to previous strategies of investigating network topologies (21, 22).”
Network Reconstruction From High-Dimensional Ordinary Differential Equations (2016, background): “However, in many systems, the additivity assumption is violated; for instance, multiplicative effects may be present in gene regulatory networks (Ma et al., 2009).”
Putting the Pieces Together: Integrative Modeling Platform Software for Structure Determination of Macromolecular Assemblies (2012, background): “A full sampling of the models of a structure can improve the understanding of its function [49].”
Feedback regulation of EGFR signalling: decision making by early and delayed loops (2011, background): “A recent study mathematically examined the architectural designs of all three-node protein circuits that can achieve adaptation, and identified only two competent topologies: a negative-feedback loop with a buffering node and an incoherent feedforward loo”
Encoding and Decoding Cellular Information through Signaling Dynamics (2013, positive): “For example, Ma et al. (2009) performed a computational search for all possible three-node enzyme network topologies to identify those that could achieve biochemical adaptation, a dynamical response that returns to baseline levels regardless of stimulus strength.”
Data Based Identification and Prediction of Nonlinear and Complex Dynamical Systems (2016, background): “Another approach is to abstract key regulation genetic networks [509, 510] (or motifs) from all associated interactions, and to employ synthetic biology to modify, control and finally understand the biological mechanisms within these complicated systems [500, 504].”