title: Evaluation of design strategies for time course experiments in genetic networks: case study of the XlnR regulon in Aspergillus niger.
abstract: One of the challenges in genetic network reconstruction is finding experimental designs that maximize the information content in a data set. In this paper, the information value of mRNA transcription time course experiments was used to compare experimental designs. The study concerns the dynamic response of genes in the XlnR regulon of Aspergillus niger, with the goal to find the best moment in time to administer an extra pulse of inducing D-xylose. Low and high D-xylose pulses were used to perturb the XlnR regulon. Evaluation of the experimental methods was based on simulation of the regulon. Models that govern the regulation of the target genes in this regulon were used for the simulations. Parameter sensitivity analysis, the Fisher Information Matrix (FIM) and the modified E-criterion were used to assess the design performances. The results show that the best time to give a second D-xylose pulse is when the D-xylose concentration from the first pulse has not yet completely faded away. Due to the presence of a repression effect the strength of the second pulse must be optimized, rather than maximized. The results suggest that the modified E-criterion is a better metric than the sum of integrals of absolute sensitivity for comparing alternative designs.
authors.affiliation: Systems and Control Group, Wageningen University, Wageningen, The Netherlands. jimmy.omony@wur.nl
authors.forename: Jimmy
authors.initials: J
authors.lastname: Omony
authors.forename: Astrid R
authors.initials: AR
authors.lastname: Mach-Aigner
authors.forename: Leo H
authors.initials: LH
authors.lastname: de Graaff
authors.forename: Gerrit
authors.initials: G
authors.lastname: van Straten
authors.forename: Anton J B
authors.initials: AJ
authors.lastname: van Boxtel
mesh_terms: D001234:Aspergillus niger / Q000235:genetics* / Q000378:metabolism; D003198:Computer Simulation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D012333:RNA, Messenger / Q000378:metabolism; D018085:Regulon / Q000235:genetics*; D014158:Transcription, Genetic; D014994:Xylose / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D012333:RNA, Messenger; D014994:Xylose