Fan-out in Gene Regulatory Networks

TL;DR

This paper introduces a method to quantify and enhance the fan-out in gene regulatory networks, aiding modular design and understanding of gene circuit interfaces in synthetic biology.

Contribution

It proposes an efficient measurement technique for fan-out, relates it to retroactivity, and shows how inhibitory regulation can improve fan-out in gene circuits.

Findings

Fan-out can be quantified using the proposed method.

Self-inhibitory regulation enhances fan-out.

The method aids modular design of gene circuits.

Abstract

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 electric engineering, to indicate the maximum number of the downstream inputs that an upstream output transcription factor can regulate. We show that the fan-out is closely related to retroactivity studied by Del Vecchio, et al. We propose an efficient operational method for measuring the fan-out that can be applied to various types of module interfaces. We also show that the fan-out can be enhanced by self-inhibitory regulation on the output. We discuss the potential role of the inhibitory regulations found in gene regulatory networks and protein signal pathways. The proposed estimation method for fanout 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.