Optimizing genetic circuits by global sensitivity analysis

Xiao Jiang Feng, Sara Hooshangi, David Chen, Genyuan Li, Ron Weiss, Herschel Rabitz

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Artificial genetic circuits are becoming important tools for controlling cellular behavior and studying molecular biosystems. To genetically optimize the properties of complex circuits in a practically feasible fashion, it is necessary to identify the best genes and/or their regulatory components as mutation targets to avoid the mutation experiments being wasted on ineffective regions, but this goal is generally not achievable by current methods. The Random Sampling - High Dimensional Model Representation (RS-HDMR) algorithm is employed in this work as a global sensitivity analysis technique to estimate the sensitivities of the circuit properties with respect to the circuit model parameters, such as rate constants, without knowing the precise parameter values. The sensitivity information can then guide the selection of the optimal mutation targets and thereby reduce the laboratory effort. As a proof of principle, the in vivo effects of 16 pairwise mutations on the properties of a genetic inverter were compared against the RS-HDMR predictions, and the algorithm not only showed good consistency with laboratory results but also revealed useful information, such as different optimal mutation targets for optimizing different circuit properties, not available from previous experiments and modeling.

Original languageEnglish (US)
Pages (from-to)2195-2202
Number of pages8
JournalBiophysical Journal
Volume87
Issue number4
DOIs
StatePublished - Oct 2004

All Science Journal Classification (ASJC) codes

  • Biophysics

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