Simultaneous Reconstruction of Multiple Signaling Pathways via the Prize-Collecting Steiner Forest Problem
Simultaneous Reconstruction of Multiple Signaling Pathways via the Prize-Collecting Steiner Forest Problem
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DOI：
10.1089/cmb.2012.0092
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发表时间：
2013-02-01
影响因子：
1.7
通讯作者：
Fraenkel, Ernest
中科院分区：
文献类型：
--
作者：
Tuncbag, Nurcan;Braunstein, Alfredo;Fraenkel, Ernest
信号传导和调节网络对于细胞控制生长、分化和对刺激的反应等过程至关重要。虽然许多“omic”数据源可用于探测信号通路，但这些数据通常是稀疏和嘈杂的。因此，很难使用这些数据来发现疾病的原因并提出新的治疗策略。我们克服了这些问题，并使用“omic”数据来同时重建在特定条件下改变的多个途径，通过解决获奖的Steiner森林问题。为了评估这种方法，我们使用的良好特性的酵母信息素反应。然后，我们将该方法应用于人类胶质母细胞瘤数据，寻找一个树木森林，每个树木都植根于不同的细胞表面受体。这种方法发现了在功能和临床相关蛋白中富集的重叠和独立的信号通路，这可以为新的治疗策略提供基础。尽管该算法没有提供关于受体磷酸化状态的任何信息，但它在相互作用物组中存在的数百种受体中鉴定了一小部分临床相关受体。
Signaling and regulatory networks are essential for cells to control processes such as growth, differentiation, and response to stimuli. Although many "omic'' data sources are available to probe signaling pathways, these data are typically sparse and noisy. Thus, it has been difficult to use these data to discover the cause of the diseases and to propose new therapeutic strategies. We overcome these problems and use "omic'' data to reconstruct simultaneously multiple pathways that are altered in a particular condition by solving the prize-collecting Steiner forest problem. To evaluate this approach, we use the well-characterized yeast pheromone response. We then apply the method to human glioblastoma data, searching for a forest of trees, each of which is rooted in a different cell-surface receptor. This approach discovers both overlapping and independent signaling pathways that are enriched in functionally and clinically relevant proteins, which could provide the basis for new therapeutic strategies. Although the algorithm was not provided with any information about the phosphorylation status of receptors, it identifies a small set of clinically relevant receptors among hundreds present in the interactome.