Optimization Alternatives for Robust Model-based Design of Synthetic Biological Circuits

摘要

Synthetic biology is reaching the situation where tuning devices by hand is no longer possible due to the complexity of the biological circuits being designed. Thus, mathematical models need to be used in order, not only to predict the behavior of the designed synthetic devices; but to help on the selection of the biological parts, i.e., guidelines for the experimental implementation. However, since uncertainties are inherent to biology, the desired dynamics for the circuit usually requires a trade-off among several goals. Hence, a multi-objective optimization design (MOOD) naturally arises to get a suitable parametrization (or range) of the required kinetic parameters to build a biological device with some desired properties. Biologists have classically addressed this problem by evaluating a set of random Monte Carlo simulations with parameters between an operation range. In this paper, we propose solving the MOOD by means of dynamic programming using both a global multi-objective evolutionary algorithm (MOEA) and a local gradient-based nonlinear programming (NLP) solver. The performance of both alternatives is then checked in the design of a well-known biological circuit: a genetic incoherent feed-forward loop showing adaptive behavior.