SynBioSS designer: a web-based tool for the automated generation of kinetic models for synthetic biological constructs

Abstract

Modeling tools can play an important role in synthetic biology the same way modeling helps in other engineering disciplines: simulations can quickly probe mechanisms and provide a clear picture of how different components influence the behavior of the whole. We present a brief review of available tools and present SynBioSS Designer. The Synthetic Biology Software Suite (SynBioSS) is used for the generation, storing, retrieval and quantitative simulation of synthetic biological networks. SynBioSS consists of three distinct components: the Desktop Simulator, the Wiki, and the Designer. SynBioSS Designer takes as input molecular parts involved in gene expression and regulation (e.g. promoters, transcription factors, ribosome binding sites, etc.), and automatically generates complete networks of reactions that represent transcription, translation, regulation, induction and degradation of those parts. Effectively, Designer uses DNA sequences as input and generates networks of biomolecular reactions as output. In this paper we describe how Designer uses universal principles of molecular biology to generate models of any arbitrary synthetic biological system. These models are useful as they explain biological phenotypic complexity in mechanistic terms. In turn, such mechanistic explanations can assist in designing synthetic biological systems. We also discuss, giving practical guidance to users, how Designer interfaces with the Registry of Standard Biological Parts, the de facto compendium of parts used in synthetic biology applications.

Synthetic Biology and Microdevices

“…This model contains an iterative design flow in which CAD models are used for the a priori design of an electronic circuit to meet the specifications of a desired system. As the engineering of biological systems is proved to be more challenging than anticipated, several groups have been developing CAD tools for synthetic biology in order to establish a similar iterative design process [Goler 2004;Chandran et al 2009;Czar et al 2009;Weeding et al 2010;Beal et al 2011;Marchisio and Stelling 2011b;Chen et al 2012].…”

“…This makes the tools strongly dependent on the information manually provided by the user. For instance, BioJADE [Goler 2004] and the Synthetic Biology Software Suite (SynBioSS) [Hill et al 2008;Weeding et al 2010] seemed promising by allowing connection to the Registry, but both tools are now outdated. While TinkerCell is regularly updated, it lacks presently a proper connection with public available libraries of biological parts [Chandran et al 2009].…”

SynBioSS-Aided Design of Synthetic Biological Constructs

“…BioBricks are synthetic DNA sequences catalogued in the Registry of Standard Biological Parts, a repository of synthetic biological constructs (Weeding et al , 2010). A BioBrick standard biological part has “a nucleic acid-encoded biological function (e.g., turn on/off gene expression), along with associated information defining and describing the part” (Shetty et al , 2008).…”

“…We have developed the Synthetic Biology Software Suite to implement this modeling approach (Hill et al , 2008; Weeding et al , 2010). An important aim for the continued development of SynBioSS is the link between synthetic DNA sequences and targeted biological functions.…”

Solution of chemical master equations for nonlinear stochastic reaction networks

“…We worked on probabilistic steady-state approximations [28], stochastic model reduction techniques [29, 30, 31], and adaptive time-stepping algorithms for stochastic differential equations [32]. We made our algorithms publicly available on sourceforge.net [33–35] and used them to simulate gene regulatory networks [36–41]. …”