Evaluation of design strategies for time course experiments in genetic networks: the XlnR regulon in Aspergillus niger

  • Authors:
  • Jimmy Omony;Astrid R. Mach-Aigner;Leo H. de Graaff;Gerrit van Straten;Anton J. B. van Boxtel

  • Affiliations:
  • Wageningen University, Wageningen, The Netherlands;Institute of Chemical Engineering, TU Wien, Wien, Austria;Wageningen University, Wageningen, The Netherlands;Wageningen University, Wageningen, The Netherlands;Wageningen University, Wageningen, The Netherlands

  • Venue:
  • Proceedings of the 9th International Conference on Computational Methods in Systems Biology
  • Year:
  • 2011

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Abstract

One of the challenges in the reconstruction of genetic network is to find experimental designs that maximize the information content in the data. In this work the information value of time course experiments (TCEs) is used to rank experimental designs. The study concerns the dynamic response of genes in the XlnR regulon of Aspergillus niger, whereby it was the goal to find the best moment to administer an extra pulse of inducing D-xylose. Low and high trigger concentrations are considered. The models that govern the regulation of the target genes in this regulon are used for simulation. Parameter sensitivity analysis, Fisher Information Matrix (FIM) and the E-modified criterion are used for the design performance assessment. The results show that the best time to give a second pulse of a low concentration trigger of D-xylose is when the D-xylose concentration from the first pulse is not yet completed reduced. Secondly, pulses with high trigger concentrations were simulated, parameter sensitivities computed, and the experimental designs evaluated. Overall, after the first pulse of 1 mM D-xylose, using a second pulse of 5 (or 10) mM D-xylose yields the best experimental design - leading to improved parameter estimates.