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整体转录互作网络:以阿尔茨海默病为例的研究

Ensemble transcript interaction networks: a case study on Alzheimer's disease.

机构信息

Departamento de Inteligencia Artificial, Universidad Politécnica de Madrid, Madrid, Spain.

出版信息

Comput Methods Programs Biomed. 2012 Oct;108(1):442-50. doi: 10.1016/j.cmpb.2011.11.011. Epub 2012 Jan 26.

Abstract

Systems biology techniques are a topic of recent interest within the neurological field. Computational intelligence (CI) addresses this holistic perspective by means of consensus or ensemble techniques ultimately capable of uncovering new and relevant findings. In this paper, we propose the application of a CI approach based on ensemble Bayesian network classifiers and multivariate feature subset selection to induce probabilistic dependences that could match or unveil biological relationships. The research focuses on the analysis of high-throughput Alzheimer's disease (AD) transcript profiling. The analysis is conducted from two perspectives. First, we compare the expression profiles of hippocampus subregion entorhinal cortex (EC) samples of AD patients and controls. Second, we use the ensemble approach to study four types of samples: EC and dentate gyrus (DG) samples from both patients and controls. Results disclose transcript interaction networks with remarkable structures and genes not directly related to AD by previous studies. The ensemble is able to identify a variety of transcripts that play key roles in other neurological pathologies. Classical statistical assessment by means of non-parametric tests confirms the relevance of the majority of the transcripts. The ensemble approach pinpoints key metabolic mechanisms that could lead to new findings in the pathogenesis and development of AD.

摘要

系统生物学技术是神经科学领域近期关注的一个主题。计算智能 (CI) 通过共识或集成技术来解决这一整体观点,最终能够揭示新的相关发现。在本文中,我们提出了一种基于集成贝叶斯网络分类器和多元特征子集选择的 CI 方法的应用,以诱导可能匹配或揭示生物学关系的概率依赖性。该研究专注于分析高通量阿尔茨海默病 (AD) 转录谱。该分析从两个角度进行。首先,我们比较了 AD 患者和对照组海马亚区内嗅皮层 (EC) 样本的表达谱。其次,我们使用集成方法研究了四种类型的样本:患者和对照组的 EC 和齿状回 (DG) 样本。结果揭示了具有显著结构的转录物相互作用网络,以及先前研究中与 AD 不直接相关的基因。该集成方法能够识别出在其他神经病理学中起关键作用的多种转录物。通过非参数检验的经典统计评估证实了大多数转录物的相关性。该集成方法指出了关键的代谢机制,这可能会导致 AD 发病机制和发展方面的新发现。

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