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Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling
BACKGROUND: The reconstruction of gene regulatory networks from time series gene expression data is one of the most difficult problems in systems biology. This is due to several reasons, among them the combinatorial explosion of possible network topologies, limited information content of the experim...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811124/ https://www.ncbi.nlm.nih.gov/pubmed/20038296 http://dx.doi.org/10.1186/1471-2105-10-448 |
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author | Mazur, Johanna Ritter, Daniel Reinelt, Gerhard Kaderali, Lars |
author_facet | Mazur, Johanna Ritter, Daniel Reinelt, Gerhard Kaderali, Lars |
author_sort | Mazur, Johanna |
collection | PubMed |
description | BACKGROUND: The reconstruction of gene regulatory networks from time series gene expression data is one of the most difficult problems in systems biology. This is due to several reasons, among them the combinatorial explosion of possible network topologies, limited information content of the experimental data with high levels of noise, and the complexity of gene regulation at the transcriptional, translational and post-translational levels. At the same time, quantitative, dynamic models, ideally with probability distributions over model topologies and parameters, are highly desirable. RESULTS: We present a novel approach to infer such models from data, based on nonlinear differential equations, which we embed into a stochastic Bayesian framework. We thus address both the stochasticity of experimental data and the need for quantitative dynamic models. Furthermore, the Bayesian framework allows it to easily integrate prior knowledge into the inference process. Using stochastic sampling from the Bayes' posterior distribution, our approach can infer different likely network topologies and model parameters along with their respective probabilities from given data. We evaluate our approach on simulated data and the challenge #3 data from the DREAM 2 initiative. On the simulated data, we study effects of different levels of noise and dataset sizes. Results on real data show that the dynamics and main regulatory interactions are correctly reconstructed. CONCLUSIONS: Our approach combines dynamic modeling using differential equations with a stochastic learning framework, thus bridging the gap between biophysical modeling and stochastic inference approaches. Results show that the method can reap the advantages of both worlds, and allows the reconstruction of biophysically accurate dynamic models from noisy data. In addition, the stochastic learning framework used permits the computation of probability distributions over models and model parameters, which holds interesting prospects for experimental design purposes. |
format | Text |
id | pubmed-2811124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28111242010-01-26 Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling Mazur, Johanna Ritter, Daniel Reinelt, Gerhard Kaderali, Lars BMC Bioinformatics Research article BACKGROUND: The reconstruction of gene regulatory networks from time series gene expression data is one of the most difficult problems in systems biology. This is due to several reasons, among them the combinatorial explosion of possible network topologies, limited information content of the experimental data with high levels of noise, and the complexity of gene regulation at the transcriptional, translational and post-translational levels. At the same time, quantitative, dynamic models, ideally with probability distributions over model topologies and parameters, are highly desirable. RESULTS: We present a novel approach to infer such models from data, based on nonlinear differential equations, which we embed into a stochastic Bayesian framework. We thus address both the stochasticity of experimental data and the need for quantitative dynamic models. Furthermore, the Bayesian framework allows it to easily integrate prior knowledge into the inference process. Using stochastic sampling from the Bayes' posterior distribution, our approach can infer different likely network topologies and model parameters along with their respective probabilities from given data. We evaluate our approach on simulated data and the challenge #3 data from the DREAM 2 initiative. On the simulated data, we study effects of different levels of noise and dataset sizes. Results on real data show that the dynamics and main regulatory interactions are correctly reconstructed. CONCLUSIONS: Our approach combines dynamic modeling using differential equations with a stochastic learning framework, thus bridging the gap between biophysical modeling and stochastic inference approaches. Results show that the method can reap the advantages of both worlds, and allows the reconstruction of biophysically accurate dynamic models from noisy data. In addition, the stochastic learning framework used permits the computation of probability distributions over models and model parameters, which holds interesting prospects for experimental design purposes. BioMed Central 2009-12-28 /pmc/articles/PMC2811124/ /pubmed/20038296 http://dx.doi.org/10.1186/1471-2105-10-448 Text en Copyright ©2009 Mazur et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research article Mazur, Johanna Ritter, Daniel Reinelt, Gerhard Kaderali, Lars Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling |
title | Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling |
title_full | Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling |
title_fullStr | Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling |
title_full_unstemmed | Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling |
title_short | Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling |
title_sort | reconstructing nonlinear dynamic models of gene regulation using stochastic sampling |
topic | Research article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811124/ https://www.ncbi.nlm.nih.gov/pubmed/20038296 http://dx.doi.org/10.1186/1471-2105-10-448 |
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