title: Reconstruction of transcriptional dynamics from gene reporter data using differential equations.
abstract: BACKGROUND
  Promoter-driven reporter genes, notably luciferase and green fluorescent protein, provide a tool for the generation of a vast array of time-course data sets from living cells and organisms. The aim of this study is to introduce a modeling framework based on stochastic differential equations (SDEs) and ordinary differential equations (ODEs) that addresses the problem of reconstructing transcription time-course profiles and associated degradation rates. The dynamical model is embedded into a Bayesian framework and inference is performed using Markov chain Monte Carlo algorithms.
  
  
  RESULTS
  We present three case studies where the methodology is used to reconstruct unobserved transcription profiles and to estimate associated degradation rates. We discuss advantages and limits of fitting either SDEs ODEs and address the problem of parameter identifiability when model variables are unobserved. We also suggest functional forms, such as on/off switches and stimulus response functions to model transcriptional dynamics and present results of fitting these to experimental data.
authors.affiliation: Department of Statistics, University of Warwick, Coventry CV47AL, UK. b.f.finkenstadt@warwick.ac.uk
authors.forename: Bärbel
authors.initials: B
authors.lastname: Finkenstädt
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Heron
authors.forename: Michal
authors.initials: M
authors.lastname: Komorowski
authors.forename: Kieron
authors.initials: K
authors.lastname: Edwards
authors.forename: Sanyi
authors.initials: S
authors.lastname: Tang
authors.forename: Claire V
authors.initials: CV
authors.lastname: Harper
authors.forename: Julian R E
authors.initials: JR
authors.lastname: Davis
authors.forename: Michael R H
authors.initials: MR
authors.lastname: White
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Millar
authors.forename: David A
authors.initials: DA
authors.lastname: Rand
mesh_terms: D000465:Algorithms; D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D003198:Computer Simulation; D017343:Genes, Plant; D017930:Genes, Reporter / Q000235:genetics*; D006801:Humans; D008390:Markov Chains; D009010:Monte Carlo Method; D051381:Rats; D014158:Transcription, Genetic