An Implementation-Focused Bio/Algorithmic Workflow for Synthetic Biology [component]

11 As synthetic biology moves away from "trial and error" and embraces more formal processes, 12 workflows have emerged that extend from the conceptualisation of a genetic device to its 13 construction and measurement. We are particularly interested in this latter aspect (i.e., 14 characterisation and measurement of synthetic genetic devices), as this is a workflow component 15 that has received relatively little attention, but is crucial to the success of such constructions. We 16 present an
more » ... d-to-end use case for engineering a basic synthetic construct, which is supported by 17 information standards and computational methods, and which focuses on characterisation and 18 measurement. This workflow captures the main stages of genetic circuit design and description, 19 and offers standardised tools for both population-based measurement and single-cell analysis. 20 The main contributions of the current paper are (1) Consideration of specific vector features. 21 Although circuit design has been successfully automated, important structural information is 22 usually overlooked, as is the case of plasmid vectors. We advocate the use of the Standard 23 European Vector Architecture to select the optimal carrier for a design and a thorough description, 24 in order to unequivocally correlate digital definitions and molecular devices. We developed a 25 digital version of this plasmid format with the Synthetic Biology Open Language and a software 26 2 tool that allows the user to embed genetic parts in vector cargoes. This enables the annotation of a 27 mathematical model of the circuit's kinetic reactions formatted with the Systems Biology Markup 28 Language. From that point onwards the experimental results and their in silico counterparts 29 proceed alongside, with constant feedback to preserve consistency between them; (2) A 30 framework for the calibration of fluorescence-based measurements in synthetic biology. One of 31 the hardest endeavours in standardisation, metrology, is addressed by reinterpreting the 32 experimental output in light of simulation results, allowing us to turn arbitrary fluorescent units 33 into relative measurements; (3) Integration of single-cell methods into a framework for 34 multicellular simulation and measurement, allowing for standardised consideration of the 35 interplay between the carrier chassis and culture conditions. 36
doi:10.1021/acssynbio.6b00029.s006 fatcat:yzgtgh245fbg3bcxlcijidam4i