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在从时间序列表达数据构建调控网络过程中整合外部生物学知识。

Integrating external biological knowledge in the construction of regulatory networks from time-series expression data.

作者信息

Lo Kenneth, Raftery Adrian E, Dombek Kenneth M, Zhu Jun, Schadt Eric E, Bumgarner Roger E, Yeung Ka Yee

机构信息

Department of Microbiology, University of Washington, Box 358070, Seattle, WA 98195, USA.

出版信息

BMC Syst Biol. 2012 Aug 16;6:101. doi: 10.1186/1752-0509-6-101.

Abstract

BACKGROUND

Inference about regulatory networks from high-throughput genomics data is of great interest in systems biology. We present a Bayesian approach to infer gene regulatory networks from time series expression data by integrating various types of biological knowledge.

RESULTS

We formulate network construction as a series of variable selection problems and use linear regression to model the data. Our method summarizes additional data sources with an informative prior probability distribution over candidate regression models. We extend the Bayesian model averaging (BMA) variable selection method to select regulators in the regression framework. We summarize the external biological knowledge by an informative prior probability distribution over the candidate regression models.

CONCLUSIONS

We demonstrate our method on simulated data and a set of time-series microarray experiments measuring the effect of a drug perturbation on gene expression levels, and show that it outperforms leading regression-based methods in the literature.

摘要

背景

从高通量基因组学数据推断调控网络是系统生物学中备受关注的问题。我们提出一种贝叶斯方法,通过整合各类生物学知识,从时间序列表达数据推断基因调控网络。

结果

我们将网络构建表述为一系列变量选择问题,并使用线性回归对数据进行建模。我们的方法通过对候选回归模型赋予信息丰富的先验概率分布来总结额外的数据源。我们扩展了贝叶斯模型平均(BMA)变量选择方法,以在回归框架中选择调控因子。我们通过对候选回归模型赋予信息丰富的先验概率分布来总结外部生物学知识。

结论

我们在模拟数据和一组测量药物扰动对基因表达水平影响的时间序列微阵列实验上展示了我们的方法,结果表明它优于文献中领先的基于回归的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a95/3465231/adfe5a1a70e7/1752-0509-6-101-1.jpg

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