Revealing functional reorganization or module rewiring between modules at network levels during drug treatment is important to systematically understand therapies and drug responses. The present article proposed a novel model of module network rewiring to characterize functional reorganization of a complex biological system, and described a new framework named as module network rewiring-analysis (MNR) for systematically studying dynamical drug sensitivity and resistance during drug treatment. MNR was used to investigate functional reorganization or rewiring on the module network, rather than molecular network or individual molecules. Our experiments on expression data of patients with Hepatitis C virus infection receiving Interferon therapy demonstrated that consistent module genes derived by MNR could be directly used to reveal new genotypes relevant to drug sensitivity, unlike the other differential analyses of gene expressions. Our results showed that functional connections and reconnections among consistent modules bridged by biological paths were necessary for achieving effective responses of a drug. The hierarchical structures of the temporal module network can be considered as spatio-temporal biomarkers to monitor the efficacy, efficiency, toxicity, and resistance of the therapy. Our study indicates that MNR is a useful tool to identify module biomarkers and further predict dynamical drug sensitivity and resistance, characterize complex dynamic processes for therapy response, and provide biologically systematic clues for pharmacogenomic applications.

中文翻译：

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通过基于转录谱的模块网络重新布线分析预测动态药物敏感性和耐药性。

在药物治疗期间，在网络级别揭示模块之间的功能重组或模块重新布线对于系统地了解疗法和药物反应非常重要。本文提出了一种新型的模块网络重新布线模型，以表征复杂生物系统的功能重组，并描述了一种名为模块网络重新布线分析（MNR）的新框架，用于系统地研究药物治疗过程中的动态药物敏感性和耐药性。MNR用于研究模块网络（而不是分子网络或单个分子）上的功能重组或重新布线。我们对接受干扰素治疗的丙型肝炎病毒感染患者的表达数据进行的实验表明，与其他基因表达差异分析不同，MNR衍生的一致模块基因可直接用于揭示与药物敏感性相关的新基因型。我们的结果表明，通过生物学途径桥接的一致模块之间的功能连接和重新连接对于实现药物的有效响应是必需的。时间模块网络的分层结构可以被视为时空生物标记，以监测治疗的功效，效率，毒性和抵抗力。我们的研究表明MNR是识别模块生物标志物并进一步预测动态药物敏感性和耐药性的有用工具，