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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.


Biological devices designed with digital targeted behavior. (a) Digital electronic circuit diagrams corresponding to the designed genetic networks. (b) On top, the time variation of the concentration of two genes, u1 and u2, chosen to be the device input genes. Below there are the resulting optimal regulatory genetic networks that more closely follow a given targeted behavior. Genes are noted with letters, and promoters with numbers according to their type (see Fig. 1). Two promoters in circuit V are noted with h (considered as hybrids), because they do not belong to the default set from Fig. 1. We targeted devices showing an AND, OR, NAND and NOR logic in terms of the input (u1 and u2) and output (a) genes. On the right, there are the corresponding time-variation of the reporter output gene concentration y. Dashed line represents the targeted behavior, and solid line the obtained evolution from the optimal genetic network. The parameters can be found in the supplementary material
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Fig7: Biological devices designed with digital targeted behavior. (a) Digital electronic circuit diagrams corresponding to the designed genetic networks. (b) On top, the time variation of the concentration of two genes, u1 and u2, chosen to be the device input genes. Below there are the resulting optimal regulatory genetic networks that more closely follow a given targeted behavior. Genes are noted with letters, and promoters with numbers according to their type (see Fig. 1). Two promoters in circuit V are noted with h (considered as hybrids), because they do not belong to the default set from Fig. 1. We targeted devices showing an AND, OR, NAND and NOR logic in terms of the input (u1 and u2) and output (a) genes. On the right, there are the corresponding time-variation of the reporter output gene concentration y. Dashed line represents the targeted behavior, and solid line the obtained evolution from the optimal genetic network. The parameters can be found in the supplementary material

Mentions: We have applied our methodology to design genetic devices behaving as logic gates. Our devices consist on genetic circuits having the concentration of two and one transcription factors as input and output, respectively. We have targeted AND, OR, NAND and NOR gates, and in Fig. 7 we show the resulting circuits. To compute the objective function we have averaged the score obtained with each transfer function corresponding to every entry of the truth table. u1 and u2 are the input transcription factors and y is the output corresponding to the concentration of gene a’s product. We have evaluated the score during 100 min. However, to better appreciate the behavior under different input conditions, we have chosen to plot a temporal dynamics where the input transcription factors concentrations u1 and u2 take all possible Boolean values of a two-input truth table. Inputs can be activators or repressors according to the chosen promoter during the simulation. In the inset of Fig. 7 we also show the equivalent digital circuits according to the interaction of each transcription factor with its corresponding promoters. We provide the parameters of those circuits in the supporting information.Fig. 7


Computational design of digital and memory biological devices.

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

Biological devices designed with digital targeted behavior. (a) Digital electronic circuit diagrams corresponding to the designed genetic networks. (b) On top, the time variation of the concentration of two genes, u1 and u2, chosen to be the device input genes. Below there are the resulting optimal regulatory genetic networks that more closely follow a given targeted behavior. Genes are noted with letters, and promoters with numbers according to their type (see Fig. 1). Two promoters in circuit V are noted with h (considered as hybrids), because they do not belong to the default set from Fig. 1. We targeted devices showing an AND, OR, NAND and NOR logic in terms of the input (u1 and u2) and output (a) genes. On the right, there are the corresponding time-variation of the reporter output gene concentration y. Dashed line represents the targeted behavior, and solid line the obtained evolution from the optimal genetic network. The parameters can be found in the supplementary material
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Related In: Results  -  Collection

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Fig7: Biological devices designed with digital targeted behavior. (a) Digital electronic circuit diagrams corresponding to the designed genetic networks. (b) On top, the time variation of the concentration of two genes, u1 and u2, chosen to be the device input genes. Below there are the resulting optimal regulatory genetic networks that more closely follow a given targeted behavior. Genes are noted with letters, and promoters with numbers according to their type (see Fig. 1). Two promoters in circuit V are noted with h (considered as hybrids), because they do not belong to the default set from Fig. 1. We targeted devices showing an AND, OR, NAND and NOR logic in terms of the input (u1 and u2) and output (a) genes. On the right, there are the corresponding time-variation of the reporter output gene concentration y. Dashed line represents the targeted behavior, and solid line the obtained evolution from the optimal genetic network. The parameters can be found in the supplementary material
Mentions: We have applied our methodology to design genetic devices behaving as logic gates. Our devices consist on genetic circuits having the concentration of two and one transcription factors as input and output, respectively. We have targeted AND, OR, NAND and NOR gates, and in Fig. 7 we show the resulting circuits. To compute the objective function we have averaged the score obtained with each transfer function corresponding to every entry of the truth table. u1 and u2 are the input transcription factors and y is the output corresponding to the concentration of gene a’s product. We have evaluated the score during 100 min. However, to better appreciate the behavior under different input conditions, we have chosen to plot a temporal dynamics where the input transcription factors concentrations u1 and u2 take all possible Boolean values of a two-input truth table. Inputs can be activators or repressors according to the chosen promoter during the simulation. In the inset of Fig. 7 we also show the equivalent digital circuits according to the interaction of each transcription factor with its corresponding promoters. We provide the parameters of those circuits in the supporting information.Fig. 7

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.