A systems-theoretic approach towards designing biological networks for perfect adaptation

Bhattacharya, Priyan; Raman, Karthik; Tangirala, Arun K.

doi:10.1016/j.ifacol.2018.05.033

Cited by 11 publications

(19 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rahi et al [ 34 ] (2017) suggested the supremacy of negative feedback loops over the incoherent feed-forward structures in the context of providing adaptation to periodic responses with varying duration for small scale network structures. We have previously employed a transfer function approach to deduce the design principles for adaptation in a three-node network [ 31 ]. The main arguments were that the condition for perfect adaptation requires the transfer function of the system to be stable and contain a zero on the origin.…”

Section: Introductionmentioning

confidence: 99%

“…This, if used for a three-protein network, produces topologies similar to the 395 topologies discussed above. Further, others have suggested specific control strategies like integral feedback to be capable of producing adaptation for a small network (containing three nodes) from an internal model principle and transfer function point of view [28][29][30][31][32][33]. Rahi et al [34] (2017) suggested the supremacy of negative feedback loops over the incoherent feed-forward structures in the context of providing adaptation to periodic responses with varying duration for small scale network structures.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Discovering adaptation-capable biological network structures using control-theoretic approaches

2022

Self Cite

View full text Add to dashboard Cite

Constructing biological networks capable of performing specific biological functionalities has been of sustained interest in synthetic biology. Adaptation is one such ubiquitous functional property, which enables every living organism to sense a change in its surroundings and return to its operating condition prior to the disturbance. In this paper, we present a generic systems theory-driven method for designing adaptive protein networks. First, we translate the necessary qualitative conditions for adaptation to mathematical constraints using the language of systems theory, which we then map back as ‘design requirements’ for the underlying networks. We go on to prove that a protein network with different input–output nodes (proteins) needs to be at least of third-order in order to provide adaptation. Next, we show that the necessary design principles obtained for a three-node network in adaptation consist of negative feedback or a feed-forward realization. We argue that presence of a particular class of negative feedback or feed-forward realization is necessary for a network of any size to provide adaptation. Further, we claim that the necessary structural conditions derived in this work are the strictest among the ones hitherto existed in the literature. Finally, we prove that the capability of producing adaptation is retained for the admissible motifs even when the output node is connected with a downstream system in a feedback fashion. This result explains how complex biological networks achieve robustness while keeping the core motifs unchanged in the context of a particular functionality. We corroborate our theoretical results with detailed and thorough numerical simulations. Overall, our results present a generic, systematic and robust framework for designing various kinds of biological networks.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Discovering adaptation-capable biological network structures using control-theoretic approaches

2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is evident from (29), S p is independent of p but a function of the effective sign of the forward path. For (26) to hold, there should be at least one pair with mutually opposed cumulative signs. This can only be possible if there exists at least one forward path with the effective sign being positive, and at least one of the remaining forward paths has to be of the effective sign negative.…”

Section: Feedforward Network Are Adaptive Only When Incoherentmentioning

confidence: 99%

“…Sontag et al [29] suggested the supremacy of negative feedback loops over the incoherent feed-forward structures in the context of providing adaptation to periodic responses with varying duration for small scale network structures. We have previously employed a transfer function approach to deduce the design principles for adaptation in a three-node network [26]. The main arguments were that the condition for perfect adaptation requires the transfer function of the system to be stable and contain a zero on the origin.…”

Section: Introductionmentioning

confidence: 99%

“…Further, others have suggested specific control strategies like integral feedback to be capable of producing adaptation for a small network (containing three nodes) from an internal model principle and transfer function point of view [23][24][25][26][27][28]. Sontag et al [29] suggested the supremacy of negative feedback loops over the incoherent feed-forward structures in the context of providing adaptation to periodic responses with varying duration for small scale network structures.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A generic systems-theoretic approach to identify biological networks capable of adaptation

Bhattacharya

Raman

Tangirala

2021

Preprint

Self Cite

View full text Add to dashboard Cite

Constructing biological networks capable of performing specific biological functionalities has been of sustained interest in synthetic biology. Adaptation is one such ubiquitous functional property, which enables every living organism to sense a change in its surroundings and return to its operating condition prior to the disturbance. In this paper, we present a generic systems theory-driven method for designing adaptive protein networks. First, we translate the necessary qualitative conditions for adaptation to mathematical constraints using the language of systems theory, which we then map back as 'design requirements' for the underlying networks. We go on to prove that a protein network with different input--output nodes (proteins) needs to be at least of third-order in order to provide adaptation. Next, we show that the necessary design principles obtained for a three-node network in adaptation consist of negative feedback or a feed-forward realization. Interestingly, the design principles obtained by the proposed method remain the same for a network of arbitrary size and connectivity. Finally, we prove that the motifs discovered for adaptation are non-retroactive for a canonical downstream connection. This result explains how complex biological networks achieve robustness while keeping the core motifs unchanged in the context of a particular functionality. We corroborate our theoretical results with detailed and thorough numerical simulations. Overall, our results present a generic, systematic and robust framework for designing various kinds of biological networks.

show abstract

Systems-Theoretic Approaches to Design Biological Networks with Desired Functionalities

Bhattacharya

Raman

Tangirala

2020

Methods in Molecular Biology

View full text Add to dashboard Cite

A systems-theoretic approach towards designing biological networks for perfect adaptation

Cited by 11 publications

References 3 publications

Discovering adaptation-capable biological network structures using control-theoretic approaches

Discovering adaptation-capable biological network structures using control-theoretic approaches

A generic systems-theoretic approach to identify biological networks capable of adaptation

Systems-Theoretic Approaches to Design Biological Networks with Desired Functionalities

Contact Info

Product

Resources

About