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Computational design of digital and memory biological devices.

Rodrigo G, Jaramillo A - Syst Synth Biol (2008)

Bottom Line: Summary.We show how to use an automated procedure to design logic and sequential transcription circuits.This methodology will allow advancing the rational design of biological devices to more complex systems, and we propose the first design of a biological JK-latch memory device.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Biologia Molecular y Celular de Plantas, CSIC-Universidad Politecnica de Valencia, Valencia, Spain.

ABSTRACT
The use of combinatorial optimization techniques with computational design allows the development of automated methods to design biological systems. Automatic design integrates design principles in an unsupervised algorithm to sample a larger region of the biological network space, at the topology and parameter levels. The design of novel synthetic transcriptional networks with targeted behaviors will be key to understand the design principles underlying biological networks. In this work, we evolve transcriptional networks towards a targeted dynamics, by using a library of promoters and coding sequences, to design a complex biological memory device. The designed sequential transcription network implements a JK-Latch, which is fully predictable and richer than other memory devices. Furthermore, we present designs of transcriptional devices behaving as logic gates, and we show how to create digital behavior from analog promoters. Our procedure allows us to propose a scenario for the evolution of multi-functional genetic networks. In addition, we discuss the decomposability of regulatory networks in terms of genetic modules to develop a given cellular function. Summary. We show how to use an automated procedure to design logic and sequential transcription circuits. This methodology will allow advancing the rational design of biological devices to more complex systems, and we propose the first design of a biological JK-latch memory device.

No MeSH data available.


Parameter sensitivity analysis for the computationally designed JK-Latch (a, b), and for the rationally designed JK-Latch (c, d). Subindex 0 refers original values
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Fig8: Parameter sensitivity analysis for the computationally designed JK-Latch (a, b), and for the rationally designed JK-Latch (c, d). Subindex 0 refers original values

Mentions: To study the robustness of our designed memory devices, we have performed a sensitivity analysis for the transcription (α) and degradation (β) rates. For that, we plot the relative score variation versus the relative parameter value (α/α0 and β/β0) for the different circuit genes. In Fig. 8a, b we show the robustness of the computationally designed JK-Latch under perturbations on C and D at the transcription and degradation level. Oppositely, in Fig. 8c, d we show the robustness of the rationally designed JK-Latch under perturbations on R and S at the transcription level and on R at the degradation level. We note that as our designs were optimized by Simulated Annealing, they are located in local minima being robust in a neighborhood of the optimized value.Fig. 8


Computational design of digital and memory biological devices.

Rodrigo G, Jaramillo A - Syst Synth Biol (2008)

Parameter sensitivity analysis for the computationally designed JK-Latch (a, b), and for the rationally designed JK-Latch (c, d). Subindex 0 refers original values
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553324&req=5

Fig8: Parameter sensitivity analysis for the computationally designed JK-Latch (a, b), and for the rationally designed JK-Latch (c, d). Subindex 0 refers original values
Mentions: To study the robustness of our designed memory devices, we have performed a sensitivity analysis for the transcription (α) and degradation (β) rates. For that, we plot the relative score variation versus the relative parameter value (α/α0 and β/β0) for the different circuit genes. In Fig. 8a, b we show the robustness of the computationally designed JK-Latch under perturbations on C and D at the transcription and degradation level. Oppositely, in Fig. 8c, d we show the robustness of the rationally designed JK-Latch under perturbations on R and S at the transcription level and on R at the degradation level. We note that as our designs were optimized by Simulated Annealing, they are located in local minima being robust in a neighborhood of the optimized value.Fig. 8

Bottom Line: Summary.We show how to use an automated procedure to design logic and sequential transcription circuits.This methodology will allow advancing the rational design of biological devices to more complex systems, and we propose the first design of a biological JK-latch memory device.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Biologia Molecular y Celular de Plantas, CSIC-Universidad Politecnica de Valencia, Valencia, Spain.

ABSTRACT
The use of combinatorial optimization techniques with computational design allows the development of automated methods to design biological systems. Automatic design integrates design principles in an unsupervised algorithm to sample a larger region of the biological network space, at the topology and parameter levels. The design of novel synthetic transcriptional networks with targeted behaviors will be key to understand the design principles underlying biological networks. In this work, we evolve transcriptional networks towards a targeted dynamics, by using a library of promoters and coding sequences, to design a complex biological memory device. The designed sequential transcription network implements a JK-Latch, which is fully predictable and richer than other memory devices. Furthermore, we present designs of transcriptional devices behaving as logic gates, and we show how to create digital behavior from analog promoters. Our procedure allows us to propose a scenario for the evolution of multi-functional genetic networks. In addition, we discuss the decomposability of regulatory networks in terms of genetic modules to develop a given cellular function. Summary. We show how to use an automated procedure to design logic and sequential transcription circuits. This methodology will allow advancing the rational design of biological devices to more complex systems, and we propose the first design of a biological JK-latch memory device.

No MeSH data available.