Reconstruction of transcriptional dynamics from gene reporter data using differential equations
Finkenstädt, Bärbel, Heron, Elizabeth A., Komorowski, Michal, Edwards, Kieron, Tang, Sanyi, Harper, Claire V., Davis, Julian R. E., White, Michael R. H., Millar, A. J. (Andrew J.) and Rand, D. A. (David A.). (2008) Reconstruction of transcriptional dynamics from gene reporter data using differential equations. Bioinformatics, Vol.24 (No.24). pp. 2901-2907. ISSN 1367-4803Full text not available from this repository.
Official URL: http://dx.doi.org/10.1093/bioinformatics/btn562
Motivation: 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.
|Item Type:||Journal Article|
|Subjects:||Q Science > QA Mathematics
Q Science > QH Natural history > QH426 Genetics
Q Science > QP Physiology
|Divisions:||Faculty of Science > Statistics
Faculty of Science > Centre for Systems Biology
|Library of Congress Subject Headings (LCSH):||Reporter genes, Transcription factors, Differential equations|
|Journal or Publication Title:||Bioinformatics|
|Publisher:||Oxford University Press|
|Official Date:||15 December 2008|
|Number of Pages:||7|
|Page Range:||pp. 2901-2907|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Engineering and Physical Sciences Research Council (EPSRC), European Union (EU), Centre for Integrative and Systems Biology (CSBE), University of Warwick. Department of Statistics, Wellcome Trust (London, England), The Prof. John Glover Memorial Postdoctoral Fellowship|
|Grant number:||E015263 (BBSRC), GR/S29256/01 (BBSRC/EPSRC), EP/C544587/1 (EPSRC), 005137 (EU), 067252 (WT)|
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