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      Chemical reaction networks for computing logarithm

      research-article
      Synthetic Biology
      Oxford University Press

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          Abstract

          Living cells constantly process information from their living environment. It has recently been shown that a number of cell signaling mechanisms (e.g. G protein-coupled receptor and epidermal growth factor) can be interpreted as computing the logarithm of the ligand concentration. This suggests that logarithm is a fundamental computation primitive in cells. There is also an increasing interest in the synthetic biology community to implement analog computation and computing the logarithm is one such example. The aim of this article is to study how the computation of logarithm can be realized using chemical reaction networks (CRNs). CRNs cannot compute logarithm exactly. A standard method is to use power series or rational function approximation to compute logarithm approximately. Although CRNs can realize these polynomial or rational function computations in a straightforward manner, the issue is that in order to be able to compute logarithm accurately over a large input range, it is necessary to use high-order approximation that results in CRNs with a large number of reactions. This article proposes a novel method to compute logarithm accurately in CRNs while keeping the number of reactions in CRNs low. The proposed method can create CRNs that can compute logarithm to different levels of accuracy by adjusting two design parameters. In this article, we present the chemical reactions required to realize the CRNs for computing logarithm. The key contribution of this article is a novel method to create CRNs that can compute logarithm accurately over a wide input range using only a small number of chemical reactions.

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          Most cited references22

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          Transcriptional regulation by the numbers: models.

          The expression of genes is regularly characterized with respect to how much, how fast, when and where. Such quantitative data demands quantitative models. Thermodynamic models are based on the assumption that the level of gene expression is proportional to the equilibrium probability that RNA polymerase (RNAP) is bound to the promoter of interest. Statistical mechanics provides a framework for computing these probabilities. Within this framework, interactions of activators, repressors, helper molecules and RNAP are described by a single function, the "regulation factor". This analysis culminates in an expression for the probability of RNA polymerase binding at the promoter of interest as a function of the number of regulatory proteins in the cell.
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            DNA as a universal substrate for chemical kinetics.

            Molecular programming aims to systematically engineer molecular and chemical systems of autonomous function and ever-increasing complexity. A key goal is to develop embedded control circuitry within a chemical system to direct molecular events. Here we show that systems of DNA molecules can be constructed that closely approximate the dynamic behavior of arbitrary systems of coupled chemical reactions. By using strand displacement reactions as a primitive, we construct reaction cascades with effectively unimolecular and bimolecular kinetics. Our construction allows individual reactions to be coupled in arbitrary ways such that reactants can participate in multiple reactions simultaneously, reproducing the desired dynamical properties. Thus arbitrary systems of chemical equations can be compiled into real chemical systems. We illustrate our method on the Lotka-Volterra oscillator, a limit-cycle oscillator, a chaotic system, and systems implementing feedback digital logic and algorithmic behavior.
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              The incoherent feedforward loop can provide fold-change detection in gene regulation.

              Many sensory systems (e.g., vision and hearing) show a response that is proportional to the fold-change in the stimulus relative to the background, a feature related to Weber's Law. Recent experiments suggest such a fold-change detection feature in signaling systems in cells: a response that depends on the fold-change in the input signal, and not on its absolute level. It is therefore of interest to find molecular mechanisms of gene regulation that can provide such fold-change detection. Here, we demonstrate theoretically that fold-change detection can be generated by one of the most common network motifs in transcription networks, the incoherent feedforward loop (I1-FFL), in which an activator regulates both a gene and a repressor of the gene. The fold-change detection feature of the I1-FFL applies to the entire shape of the response, including its amplitude and duration, and is valid for a wide range of biochemical parameters.
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                Author and article information

                Journal
                Synth Biol (Oxf)
                Synth Biol (Oxf)
                synbio
                Synthetic Biology
                Oxford University Press
                2397-7000
                January 2017
                28 April 2017
                28 April 2017
                : 2
                : 1
                : ysx002
                Affiliations
                School of Computer Science and Engineering, University of New South Wales, Sydney, NSW, Australia
                Author notes
                [* ]Corresponding author: E-mail: ctchou@ 123456cse.unsw.edu.au
                Article
                ysx002
                10.1093/synbio/ysx002
                7513738
                1be062a7-5ff4-46a3-9cdc-71d1c1799863
                © The Author 2017. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 29 December 2016
                : 20 March 2017
                : 23 March 2017
                Page count
                Pages: 13
                Categories
                Research Article

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