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

Statistical inference of the time-varying structure of gene-regulation networks.
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DOI:
10.1186/1752-0509-4-130
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发表时间:
2010-09-22
影响因子:
--
通讯作者:
Lelandais G
Lelandais G
中科院分区:
生物2区
文献类型:
--
作者:
Lèbre S;Becq J;Devaux F;Stumpf MP;Lelandais G

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生物网络对环境和生理线索的反应是高度动态的。这种可变性与传统的生物网络分析形成鲜明对比,传统的生物网络分析绝大多数采用静态图模型,这些模型随着时间的推移保持不变来描述生物系统及其潜在的分子相互作用。为了克服这些限制,我们在这里提出了一种新的统计建模框架,即 ARTIVA 形式主义(自回归时间变化模型),以及相关的推理程序,使我们能够从生物时程表达数据中学习随时间变化的基因调控网络。 ARTIVA 同时推断监管网络的拓扑结构以及它如何随时间变化。它使我们能够恢复参与特定生物过程(发育、应激反应等)的单个基因的调控关联的年表。我们证明,ARTIVA 方法可以对复杂生物系统的功能和动力学产生详细的见解,并有效地利用系统生物学中的时程数据。特别是分析了两种生物学情景:黑腹果蝇的发育阶段和酿酒酵母对苯菌灵中毒的反应。 ARTIVA 确实从转录数据中恢复了生物系统中基本的时间依赖性,并提供了一个自然的起点来更详细地学习和研究其动态。
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. 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.). 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. 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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