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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >A systems biology approach for the study of cumulative oncogenes with applications to the MAPK signal transduction pathway.
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A systems biology approach for the study of cumulative oncogenes with applications to the MAPK signal transduction pathway.

机译：一种系统生物学方法，用于研究累积的致癌基因及其在MAPK信号转导途径中的应用。

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The Extracellular signal Regulated Kinase (ERK) pathway is one of the most well-studied signaling pathways in cell cycle regulation. Disruption in the normal functioning of this pathway is linked to many forms of cancer. In a previous study [D.K. Pant, A. Ghosh, Automated oncogene detection in complex protein networks, with applications to the MAPK signal transduction pathway, Biophys. Chem. 113 (2005) 275-288.], we developed a novel approach to predict single point mutations that are likely to cause cellular transformation in signaling transduction networks. We have extended this method to study disparate pair mutation in enzyme/protein interactions and in expression levels in signal transduction pathway and have applied it to the MAPK signaling pathway to study how synergistic or cooperative mutation within signaling networks acts in unison to cause malignant transformation. The method provides a quantitative ranking of the modifier pair of ERK activation. It is seen that the highest ranking single point mutations comprise the highest ranking pair mutations. We validate some of our results with experimental literature on multiple mutations. A second order sensitivity analysis scheme is additionally used to determine the effect of correlations among mutations at different sites in the pathways.
机译：细胞外信号调节激酶（ERK）途径是细胞周期调控中研究最深入的信号途径之一。该途径正常功能的破坏与多种形式的癌症有关。在先前的研究中Pant，A。Ghosh，复杂蛋白质网络中的癌基因自动检测，应用于MAPK信号转导途径，Biophys。化学113（2005）275-288。]，我们开发了一种新颖的方法来预测可能在信号转导网络中引起细胞转化的单点突变。我们已经扩展了该方法，以研究酶/蛋白质相互作用中不同的成对突变以及信号转导途径中的表达水平，并将其应用于MAPK信号通路中，以研究信号网络内的协同或合作突变如何一致地引起恶性转化。该方法提供了ERK活化的修饰子对的定量排名。可以看出，最高等级的单点突变包括最高等级的对突变。我们用关于多种突变的实验文献验证了我们的一些结果。另外使用二阶敏感性分析方案来确定途径中不同位点的突变之间的相关性影响。

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