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一致性概率的降低:处于生物系统灾难性转变的十字路口。

The decrease of consistence probability: at the crossroad of catastrophic transition of a biological system.

作者信息

Chen Pei, Li Yongjun

机构信息

School of Computer Science and Engineering, Wushan Road, 510640, Guangzhou, China.

出版信息

BMC Syst Biol. 2016 Aug 1;10 Suppl 2(Suppl 2):50. doi: 10.1186/s12918-016-0295-y.

Abstract

BACKGROUND

Unlike traditional detection of a disease state in which there are clear phenomena, it is usually a challenge to identify the pre-disease state during the progression of a complex disease just before the serious deterioration, not only because of the high complexity of the biological system, but there may be few clues and apparent changes appearing until the catastrophic critical transition occurs.

RESULTS

In this work, by exploiting the different dynamical features between the normal and pre-disease states, we present a hidden-Markov-model (HMM) based computational method to identify the pre-disease state and elucidate the essential mechanisms during the critical transition at the network level. Specifically, by considering the network variation and regarding that the pre-disease state is the end or shift-point of a stationary Markov process, a consistence score is proposed to measure the probability that a system is in consistency with the normal state. As validation, this approach is applied to detect the upcoming critical transition of complex systems based on both the dataset generated from a simulated network and the rich information provided by high-throughput microarray data. The effectiveness of our method has been demonstrated by the identification of the pre-disease states for two real datasets including HCV-induced hepatocellular carcinoma and virus-induced influenza infection.

CONCLUSION

From dynamical view point, the critical-transition phenomena in many biological processes are of some generic properties, which can be detected by the established method.

摘要

背景

与传统的疾病状态检测不同,传统检测中有明确的现象,而在复杂疾病进展过程中,在严重恶化之前识别疾病前状态通常是一项挑战,这不仅是因为生物系统高度复杂,而且在灾难性的临界转变发生之前可能几乎没有线索和明显变化出现。

结果

在这项工作中,通过利用正常状态和疾病前状态之间不同的动力学特征,我们提出了一种基于隐马尔可夫模型(HMM)的计算方法,以在网络层面识别疾病前状态并阐明临界转变过程中的基本机制。具体而言,通过考虑网络变化并将疾病前状态视为平稳马尔可夫过程的终点或转折点,提出了一个一致性得分来衡量系统与正常状态一致的概率。作为验证,该方法基于从模拟网络生成的数据集以及高通量微阵列数据提供的丰富信息,应用于检测复杂系统即将到来的临界转变。我们的方法通过识别包括丙型肝炎病毒诱导的肝细胞癌和病毒诱导的流感感染在内的两个真实数据集的疾病前状态,证明了其有效性。

结论

从动力学角度来看,许多生物过程中的临界转变现象具有一些通用特性,可以通过所建立的方法进行检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6001/4977482/6cd0dbcd1142/12918_2016_295_Fig1_HTML.jpg

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