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首页> 外文期刊>EURASIP journal on bioinformatics and systems biology >Computing interaction probabilities in signaling networks
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Computing interaction probabilities in signaling networks

机译:计算信令网络中的交互概率

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摘要

Biological networks inherently have uncertain topologies. This arises from many factors. For instance, interactions between molecules may or may not take place under varying conditions. Genetic or epigenetic mutations may also alter biological processes like transcription or translation. This uncertainty is often modeled by associating each interaction with a probability value. Studying biological networks under this probabilistic model has already been shown to yield accurate and insightful analysis of interaction data. However, the problem of assigning accurate probability values to interactions remains unresolved. In this paper, we present a novel method for computing interaction probabilities in signaling networks based on transcription levels of genes. The transcription levels define the signal reachability probability between membrane receptors and transcription factors. Our method computes the interaction probabilities that minimize the gap between the observed and the computed signal reachability probabilities. We evaluate our method on four signaling networks from the Kyoto Encyclopedia of Genes and Genomes (KEGG). For each network, we compute its edge probabilities using the gene expression profiles for seven major leukemia subtypes. We use these values to analyze how the stress induced by different leukemia subtypes affects signaling interactions.
机译:生物网络固有地具有不确定的拓扑。这是由许多因素引起的。例如,分子之间的相互作用可以在变化的条件下发生或不发生。遗传或表观遗传突变也可能改变生物过程,例如转录或翻译。通常通过将每个交互与一个概率值相关联来对这种不确定性进行建模。在这种概率模型下研究生物网络已经显示出可以对相互作用数据进行准确而有见地的分析。但是,仍未解决为交互分配准确的概率值的问题。在本文中,我们提出了一种基于基因转录水平计算信号网络中相互作用概率的新方法。转录水平定义了膜受体和转录因子之间的信号可达性概率。我们的方法计算的交互概率使观察到的信号可达性与计算得出的信号之间的差距最小。我们在《京都基因与基因组百科全书》(KEGG)的四个信号网络上评估了我们的方法。对于每个网络,我们使用七个主要白血病亚型的基因表达谱来计算其边缘概率。我们使用这些值来分析由不同的白血病亚型诱导的压力如何影响信号相互作用。

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