Designing synthetic networks in silico: A generalised evolutionary algorithm approach

Abstract

Background: Evolution has led to the development of biological networks that are shaped by environmental signals. Elucidating, understanding and then reconstructing important network motifs is one of the principal aims of Systems & Synthetic Biology. Consequently, previous research has focused on finding optimal network structures and reaction rates that respond to pulses or produce stable oscillations. In this work we present a generalised in silico evolutionary algorithm that simultaneously finds network structures and reaction rates (genotypes) that can satisfy multiple defined objectives (phenotypes). Results: The key step to our approach is to translate a schema/binary-based description of biological networks into systems of ordinary differential equations (ODEs). The ODEs can then be solved numerically to provide dynamic information about an evolved networks functionality. Initially we benchmark algorithm performance by finding optimal networks that can recapitulate concentration time-series data and perform parameter optimisation on oscillatory dynamics of the Repressilator. We go on to show the utility of our algorithm by finding new designs for robust synthetic oscillators, and by performing multi-objective optimisation to find a set of oscillators and feed-forward loops that are optimal at balancing different system properties. In sum, our results not only confirm and build on previous observations but we also provide new designs of synthetic oscillators for experimental construction. Conclusions: In this work we have presented and tested an evolutionary algorithm that can design a biological network to produce desired output. Given that previous designs of synthetic networks have been limited to subregions of network- and parameter-space, the use of our evolutionary optimisation algorithm will enable Synthetic Biologists to construct new systems with the potential to display a wider range of complex responses.