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散发性包涵体肌炎潜在分子网络的图形建模

Graphical modelling of molecular networks underlying sporadic inclusion body myositis.

作者信息

Thorne Thomas, Fratta Pietro, Hanna Michael G, Cortese Andrea, Plagnol Vincent, Fisher Elizabeth M, Stumpf Michael P H

机构信息

Centre for Bioinformatics and Systems Biology, Imperial College London, London, UK.

出版信息

Mol Biosyst. 2013 Jul;9(7):1736-42. doi: 10.1039/c3mb25497f. Epub 2013 Apr 17.

Abstract

Here we present a novel statistical methodology that allows us to analyze gene expression data that have been collected from a number of different cases or conditions in a unified framework. Using a Bayesian nonparametric framework we develop a hierarchical model wherein genes can maintain a shared set of interactions between different cases, whilst also exhibiting behaviour that is unique to specific cases, sets of conditions, or groups of data points. By doing so we are able to not only combine data from different cases but also to discern the unique regulatory interactions that differentiate the cases. We apply our method to clinical data collected from patients suffering from sporadic Inclusion Body Myositis (sIBM), as well as control samples, and demonstrate the ability of our method to infer regulatory interactions that are unique to the disease cases of interest. The method thus balances the statistical need to include as many patients and controls as possible, and the clinical need to maintain potentially cryptic differences among patients and between patients and controls at the regulatory level.

摘要

在此,我们提出了一种新颖的统计方法,该方法使我们能够在统一框架内分析从多个不同病例或条件中收集到的基因表达数据。使用贝叶斯非参数框架,我们开发了一种层次模型,其中基因可以在不同病例之间保持一组共享的相互作用,同时还表现出特定病例、条件集或数据点组所特有的行为。通过这样做,我们不仅能够合并来自不同病例的数据,还能够辨别区分这些病例的独特调控相互作用。我们将我们的方法应用于从散发性包涵体肌炎(sIBM)患者以及对照样本中收集的临床数据,并证明了我们的方法能够推断出感兴趣的疾病病例所特有的调控相互作用。因此,该方法平衡了尽可能纳入更多患者和对照的统计需求,以及在调控水平上保持患者之间以及患者与对照之间潜在隐秘差异的临床需求。

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