automatic design of digital synthetic gene circuits数字合成基因电路自动设计.pdf

Automatic Design of Digital Synthetic Gene Circuits ¨ Mario A. Marchisio, Jorg Stelling* Department of Biosystems Science and Engineering and Swiss Institute of Bioinformatics, ETH Zurich, Basel, Switzerland Abstract De novo computational design of synthetic gene circuits that achieve well-defined target functions is a hard task. Existing, brute-force approaches run optimization algorithms on the structure and on the kinetic parameter values of the network. However, more direct rational methods for automatic circuit design are lacking. Focusing on digital synthetic gene circuits, we developed a methodology and a corresponding tool for in silico automatic design. For a given truth table that specifies a circuit’s input–output relations, our algorithm generates and ranks several possible circuit schemes without the need for any optimization. Logic behavior is reproduced by the action of regulatory factors and chemicals on the promoters and on the ribosome binding sites of biological Boolean gates. Simulations of circuits with up to four inputs show a faithful and unequivocal truth table representation, even under parametric perturbations and stochastic noise. A comparison with already implemented circuits, in addition, reveals the potential for simpler designs with the same function. Therefore, we expect the method to help both in devising new circuits and in simplifying existing solutions. Citation: Marchisio MA, Stelling J (2011) Automatic Design of Digital Synthetic Gene Circuits. PLoS Comput Biol 7(2): e1001083. doi:10.1371/journal.pcbi.1001083 Editor: Jason A. Papin, University of Virginia, United States of America Received July 22, 2010; Accepted January 13, 2011; Published February 17, 2011 Copyright: 2011 Marchisio, Stelling. This is an open-access article distributed under the terms of the Creative Commons At