Identifying critical transitions and their leading biomolecular networks in complex diseases.

Identifying critical transitions and their leading biomolecular networks in complex diseases.
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DOI:
10.1038/srep00813
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发表时间:
2012
期刊:
影响因子:
4.6
通讯作者:
Aihara, Kazuyuki
Aihara, Kazuyuki
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu, Rui;Li, Meiyi;Liu, Zhi-Ping;Wu, Jiarui;Chen, Luonan;Aihara, Kazuyuki

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在复杂疾病的发生和发展过程中识别关键转变及其主导的生物分子网络是一项具有挑战性的任务,但它是早期诊断和进一步阐明网络水平疾病恶化的基本机制的关键。在这项研究中,我们开发了一种新的计算方法,用于识别疾病进展过程中关键转变及其主导网络的预警信号,该方法基于使用少量样本的高通量数据。主导网络在过渡期间从正常状态向疾病状态的第一个移动,因此与疾病驱动基因或网络有因果关系。具体来说,我们首先定义了一个基于状态转换的局部网络熵(SNE),并证明了SNE可以作为一个通用的预警指标,任何即将发生的过渡,而不管系统之间的具体差异。函数分析和实验数据验证了该方法的有效性。
Identifying a critical transition and its leading biomolecular network during the initiation and progression of a complex disease is a challenging task, but holds the key to early diagnosis and further elucidation of the essential mechanisms of disease deterioration at the network level. In this study, we developed a novel computational method for identifying early-warning signals of the critical transition and its leading network during a disease progression, based on high-throughput data using a small number of samples. The leading network makes the first move from the normal state toward the disease state during a transition, and thus is causally related with disease-driving genes or networks. Specifically, we first define a state-transition-based local network entropy (SNE), and prove that SNE can serve as a general early-warning indicator of any imminent transitions, regardless of specific differences among systems. The effectiveness of this method was validated by functional analysis and experimental data.
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