Optimally Designed Model Selection for Synthetic Biology.
ACS Synth Biol
; 9(11): 3134-3144, 2020 11 20.
Article
en En
| MEDLINE
| ID: mdl-33152239
ABSTRACT
Modeling parts and circuits represents a significant roadblock to automating the Design-Build-Test-Learn cycle in synthetic biology. Once models are developed, discriminating among them requires informative data, computational resources, and skills that might not be readily available. The high cost entailed in model discrimination frequently leads to subjective choices on the selected structures and, in turn, to suboptimal models. Here, we outline frequentist and Bayesian approaches to model discrimination. We ranked three candidate models of a genetic toggle switch, which was adopted as a test case, according to the support from in vivo data. We show that, in each framework, efficient model discrimination can be achieved via optimally designed experiments. We offer a dynamical-systems interpretation of our optimization results and investigate their sensitivity to key parameters in the characterization of synthetic circuits. Our approach suggests that optimal experimental design is an effective strategy to discriminate between competing models of a gene regulatory network. Independent of the adopted framework, optimally designed perturbations exploit regions in the input space that maximally distinguish predictions from the competing models.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biología Sintética
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
ACS Synth Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido