Fan-out in Gene Regulatory Networks. J Biol Eng 4:16

Department of Bioengineering, University of Washington, William H, Foege Building, Box 355061, Seattle, WA 98195-5061, USA. .
Journal of Biological Engineering (Impact Factor: 2.48). 12/2010; 4(1):16. DOI: 10.1186/1754-1611-4-16
Source: PubMed


In synthetic biology, gene regulatory circuits are often constructed by combining smaller circuit components. Connections between components are achieved by transcription factors acting on promoters. If the individual components behave as true modules and certain module interface conditions are satisfied, the function of the composite circuits can in principle be predicted.
In this paper, we investigate one of the interface conditions: fan-out. We quantify the fan-out, a concept widely used in electrical engineering, to indicate the maximum number of the downstream inputs that an upstream output transcription factor can regulate. The fan-out is shown to be closely related to retroactivity studied by Del Vecchio, et al. An efficient operational method for measuring the fan-out is proposed and shown to be applied to various types of module interfaces. The fan-out is also shown to be enhanced by self-inhibitory regulation on the output. The potential role of an inhibitory regulation is discussed.
The proposed estimation method for fan-out not only provides an experimentally efficient way for quantifying the level of modularity in gene regulatory circuits but also helps characterize and design module interfaces, enabling the modular construction of gene circuits.

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Available from: Herbert M Sauro, May 20, 2015
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    • "A precise gate wiring needs a more detailed promoter characterization with a better estimation of operator positional effects and leakage. Furthermore, the fan-out[37] of every gate has to be determined properly. Distributed output architecture, in contrast, demands that basic gates have similar performance–namely comparable output fluorescence levels–such that one can predict and clearly distinguish the 0 and 1 output of the circuit realized via gates’ composition. "
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    • "● Approximate knowledge of RNA folding and cis-/transinteraction of multiple regulators [13] [16]. ● Functional composition of devices that leads to unexpected circuit failure [20] [21] [22] [23]. "
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    ABSTRACT: Modularity is a concept that is widely used in biological science with various interpretations. In this chapter we will first give a general overview of modularity in biology, and later focus on modularity in synthetic biology. In engineering, a module is a component whose intrinsic functionality is independent of its surrounding milieu. In biology, however, modularity is less clear-cut; for example, modules can be classified by network interactions or by functional distinctiveness such as the reuse of protein domains. In synthetic biology the question of modularity is more closely related to engineering where functional independence is important. One way of defining synthetic modules is by specifying a generic pattern of regulations that results in desired functionalities, which we term a design pattern. In this perspective, connections between modules are described by the regulatory links, which are represented by molecular reactions. Under these reactions, the output of an upstream module – the concentration of regulating molecules – is sequestered by the input of the downstream module. This sequestration can cause changes in the upstream module function. We quantify the maximally tolerable load from the downstream input, which we term gene circuit fan-out. We provide an efficient and practical way of estimating the fan-out by experiment.
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