Reconstructing dynamic regulatory maps.

Reconstructing dynamic regulatory maps.
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DOI:
10.1038/msb4100115
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发表时间:
2007
影响因子:
9.9
通讯作者:
--
中科院分区:
生物学1区
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--
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即使是简单的生物体也有能力对内部和外部刺激做出反应。这种反应是通过蛋白质-DNA相互作用的动态网络进行的,该网络允许对反应所需的基因进行特异性调节。我们已经开发了一种新的计算方法,使用输入输出隐马尔可夫模型来模拟这些监管网络,同时考虑到它们的动态特性。我们的方法通过识别分叉点来工作,分叉点是时间序列中一个基因子集的表达与其余基因的表达不同的地方。这些点与调节这些转换的转录因子一起注释,从而产生统一的时间图。应用我们的方法来研究酵母对压力的反应,我们推导出能够恢复这些反应的许多已知方面的动态模型。通过我们的方法所作的预测已经过实验验证,导致Ino 4和Gcn 4在控制酵母对压力的反应中发挥新的作用。时间级联的因素揭示了共同的途径,并突出了主和次要因素之间的差异,在利用网络图案和条件特异性调节。
Even simple organisms have the ability to respond to internal and external stimuli. This response is carried out by a dynamic network of protein–DNA interactions that allows the specific regulation of genes needed for the response. We have developed a novel computational method that uses an input–output hidden Markov model to model these regulatory networks while taking into account their dynamic nature. Our method works by identifying bifurcation points, places in the time series where the expression of a subset of genes diverges from the rest of the genes. These points are annotated with the transcription factors regulating these transitions resulting in a unified temporal map. Applying our method to study yeast response to stress, we derive dynamic models that are able to recover many of the known aspects of these responses. Predictions made by our method have been experimentally validated leading to new roles for Ino4 and Gcn4 in controlling yeast response to stress. The temporal cascade of factors reveals common pathways and highlights differences between master and secondary factors in the utilization of network motifs and in condition-specific regulation.
DOI: 10.1073/pnas.98.4.1693
发表时间: 2001-02-13
影响因子: 11.1
作者:
Holter, NS;Maritan, A;Banavar, JR
通讯作者: Banavar, JR
DOI: 10.1038/ng941
发表时间: 2002-08-01
期刊: NATURE GENETICS
影响因子: 30.8
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影响因子: 5.3
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DOI: 10.1128/mcb.10.6.2458
发表时间: 1990-06-01
影响因子: 5.3
作者:
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通讯作者: MASISON, DC
DOI: 10.1073/pnas.80.17.5374
发表时间: 1983-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
HINNEBUSCH, AG;FINK, GR
通讯作者: FINK, GR