ExprEssence--revealing the essence of differential experimental data in the context of an interaction/regulation net-work.

ExprEssence--revealing the essence of differential experimental data in the context of an interaction/regulation net-work.
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表达式 - 在相互作用/调节网络工作的背景下,将差异实验数据的本质进行视为。

DOI:
10.1186/1752-0509-4-164
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发表时间:
2010-11-30
影响因子:
--
通讯作者:
Fuellen G
Fuellen G
中科院分区:
生物2区
文献类型:
--
作者:
Warsow G;Greber B;Falk SS;Harder C;Siatkowski M;Schordan S;Som A;Endlich N;Schöler H;Repsilber D;Endlich K;Fuellen G

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实验主义者被高通量数据淹没,迫切需要将信息浓缩成简单的假设。例如,大量的微阵列和深度测序数据正在变得可用,描述了各种实验条件,如基因敲除和敲低,干预的效果以及组织和细胞系之间的差异。为了应对这一挑战,我们开发了一种方法,作为Cytoscape插件ExprEssence实现。作为输入,我们采用基因/蛋白质之间的相互作用,刺激和/或抑制联系的网络,以及差异数据,如基因表达数据,及时跟踪干预或发展。我们浓缩了网络,突出了那些可以观察到最大变化的链接。突出显示是基于一个简单的公式,灵感来自质量作用定律。我们可以交互式地修改阈值以突出显示并即时可视化结果。我们将ExprEssence应用于描述肾脏足细胞生物学、多能性和衰老的三种情况:1)我们确定了参与足细胞分化(去分化)的假定过程,并通过实验验证了一个预测。2)我们预测并验证了参与多能性的转录因子的表达水平。3)最后,我们产生合理的假设,从海马体中获得的老化数据中的细胞凋亡,细胞周期失调和DNA修复的作用。将基因/蛋白质网络的大小减少到受大变化影响的少数环节,可以筛选参与适应不同实验条件的基因/蛋白质之间的假定机制关系,产生重要的假设,见解和新实验的建议。我们注意到,我们不关注“活动子网”的识别。相反,我们专注于识别单个链接(可能会或可能不会形成子网络),这些单个链接比子模块更容易通过实验验证。ExprEssence可在http://sourceforge.net/projects/expressence/上获得。
Experimentalists are overwhelmed by high-throughput data and there is an urgent need to condense information into simple hypotheses. For example, large amounts of microarray and deep sequencing data are becoming available, describing a variety of experimental conditions such as gene knockout and knockdown, the effect of interventions, and the differences between tissues and cell lines. To address this challenge, we developed a method, implemented as a Cytoscape plugin called ExprEssence. As input we take a network of interaction, stimulation and/or inhibition links between genes/proteins, and differential data, such as gene expression data, tracking an intervention or development in time. We condense the network, highlighting those links across which the largest changes can be observed. Highlighting is based on a simple formula inspired by the law of mass action. We can interactively modify the threshold for highlighting and instantaneously visualize results. We applied ExprEssence to three scenarios describing kidney podocyte biology, pluripotency and ageing: 1) We identify putative processes involved in podocyte (de-)differentiation and validate one prediction experimentally. 2) We predict and validate the expression level of a transcription factor involved in pluripotency. 3) Finally, we generate plausible hypotheses on the role of apoptosis, cell cycle deregulation and DNA repair in ageing data obtained from the hippocampus. Reducing the size of gene/protein networks to the few links affected by large changes allows to screen for putative mechanistic relationships among the genes/proteins that are involved in adaptation to different experimental conditions, yielding important hypotheses, insights and suggestions for new experiments. We note that we do not focus on the identification of 'active subnetworks'. Instead we focus on the identification of single links (which may or may not form subnetworks), and these single links are much easier to validate experimentally than submodules. ExprEssence is available at http://sourceforge.net/projects/expressence/.
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期刊: PloS one
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