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This article is part of the supplement: Selected articles from the 10th International Workshop on Computational Systems Biology (WCSB) 2013: Bioinformatics

Open Access Research

Mapping behavioral specifications to model parameters in synthetic biology

Heinz Koeppl12*, Marc Hafner3 and James Lu4

Author Affiliations

1 ETH Zurich, Zurich, Switzerland

2 IBM Zurich Research Laboratory, Rueschlikon, Switzerland

3 Harvard Medical School, Boston MA, USA

4 F. Hoffmann-La Roche, Basel, Switzerland

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BMC Bioinformatics 2013, 14(Suppl 10):S9  doi:10.1186/1471-2105-14-S10-S9

Published: 12 August 2013

Abstract

With recent improvements of protocols for the assembly of transcriptional parts, synthetic biological devices can now more reliably be assembled according to a given design. The standardization of parts open up the way for in silico design tools that improve the construct and optimize devices with respect to given formal design specifications. The simplest such optimization is the selection of kinetic parameters and protein abundances such that the specified design constraints are robustly satisfied. In this work we address the problem of determining parameter values that fulfill specifications expressed in terms of a functional on the trajectories of a dynamical model. We solve this inverse problem by linearizing the forward operator that maps parameter sets to specifications, and then inverting it locally. This approach has two advantages over brute-force random sampling. First, the linearization approach allows us to map back intervals instead of points and second, every obtained value in the parameter region is satisfying the specifications by construction. The method is general and can hence be incorporated in a pipeline for the rational forward design of arbitrary devices in synthetic biology.