title: Bifurcation analysis informs Bayesian inference in the Hes1 feedback loop.
abstract: BACKGROUND
  Ordinary differential equations (ODEs) are an important tool for describing the dynamics of biological systems. However, for ODE models to be useful, their parameters must first be calibrated. Parameter estimation, that is, finding parameter values given experimental data, is an inference problem that can be treated systematically through a Bayesian framework.A Markov chain Monte Carlo approach can then be used to sample from the appropriate posterior probability distributions, provided that suitable prior distributions can be found for the unknown parameter values. Choosing these priors is therefore a vital first step in the inference process. We study here a negative feedback loop in gene regulation where an ODE incorporating a time delay has been proposed as a realistic model and where experimental data is available. Our aim is to show that a priori mathematical analysis can be exploited in the choice of priors.
  
  
  RESULTS
  By focussing on the onset of oscillatory behaviour through a Hopf Bifurcation, we derive a range of analytical expressions and constraints that link the model parameters to the observed dynamics of the system. Computational tests on both simulated and experimental data emphasise the usefulness of this analysis.
  
  
  CONCLUSIONS
  Mathematical analysis not only gives insights into the possible dynamical behaviour of gene expression models, but can also be used to inform the choice of priors when parameters are inferred from experimental data in a Bayesian setting.
authors.affiliation: Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK. c.higham.1@research.gla.ac.uk
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Higham
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001499:Bayes Theorem; D025461:Feedback, Physiological; D053263:Gene Regulatory Networks; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D012333:RNA, Messenger