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Statistical inference of the time-varying structure of gene-regulation networks
Article de revue scientifique   Avec comité de lecture

Statistical inference of the time-varying structure of gene-regulation networks

Sophie Lèbre, Jennifer Becq, Frédéric Devaux, Michael Stumpf et Gaëlle Lelandais
BMC systems biology, Vol.4(1), p.130-130
22/09/2010
PMID: 20860793

Résumé

Algorithms Animals Benomyl Biochemistry, Molecular Biology Bioinformatics Computer Science Drosophila melanogaster Gene Regulatory Networks Genomics Life Sciences Markov Chains Models, Genetic Monte Carlo Method Quantitative Methods Regression Analysis Reproducibility of Results Saccharomyces cerevisiae Transcription Factors
BACKGROUND: Biological networks are highly dynamic in response to environmental and physiological cues. This variability is in contrast to conventional analyses of biological networks, which have overwhelmingly employed static graph models which stay constant over time to describe biological systems and their underlying molecular interactions. METHODS: To overcome these limitations, we propose here a new statistical modelling framework, the ARTIVA formalism (Auto Regressive TIme VArying models), and an associated inferential procedure that allows us to learn temporally varying gene-regulation networks from biological time-course expression data. ARTIVA simultaneously infers the topology of a regulatory network and how it changes over time. It allows us to recover the chronology of regulatory associations for individual genes involved in a specific biological process (development, stress response, etc.). RESULTS: We demonstrate that the ARTIVA approach generates detailed insights into the function and dynamics of complex biological systems and exploits efficiently time-course data in systems biology. In particular, two biological scenarios are analyzed: the developmental stages of Drosophila melanogaster and the response of Saccharomyces cerevisiae to benomyl poisoning. CONCLUSIONS: ARTIVA does recover essential temporal dependencies in biological systems from transcriptional data, and provide a natural starting point to learn and investigate their dynamics in greater detail.

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