title: Inference of dynamical gene-regulatory networks based on time-resolved multi-stimuli multi-experiment data applying NetGenerator V2.0.
abstract: BACKGROUND
  Inference of gene-regulatory networks (GRNs) is important for understanding behaviour and potential treatment of biological systems. Knowledge about GRNs gained from transcriptome analysis can be increased by multiple experiments and/or multiple stimuli. Since GRNs are complex and dynamical, appropriate methods and algorithms are needed for constructing models describing these dynamics. Algorithms based on heuristic approaches reduce the effort in parameter identification and computation time.
  
  
  RESULTS
  The NetGenerator V2.0 algorithm, a heuristic for network inference, is proposed and described. It automatically generates a system of differential equations modelling structure and dynamics of the network based on time-resolved gene expression data. In contrast to a previous version, the inference considers multi-stimuli multi-experiment data and contains different methods for integrating prior knowledge. The resulting significant changes in the algorithmic procedures are explained in detail. NetGenerator is applied to relevant benchmark examples evaluating the inference for data from experiments with different stimuli. Also, the underlying GRN of chondrogenic differentiation, a real-world multi-stimulus problem, is inferred and analysed.
  
  
  CONCLUSIONS
  NetGenerator is able to determine the structure and parameters of GRNs and their dynamics. The new features of the algorithm extend the range of possible experimental set-ups, results and biological interpretations. Based upon benchmarks, the algorithm provides good results in terms of specificity, sensitivity, efficiency and model fit.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.forename: Sebastian G
authors.initials: SG
authors.lastname: Henkel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vlaic
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.forename: Everardus J
authors.initials: EJ
authors.lastname: van Zoelen
authors.forename: Dominik
authors.initials: D
authors.lastname: Driesch
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks / Q000235:genetics*; D008957:Models, Genetic; D012680:Sensitivity and Specificity; D012984:Software; D013997:Time Factors