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用于非参数微分方程模型的稳健变量选择方法及其在非线性动态基因调控网络分析中的应用

Robust variable selection method for nonparametric differential equation models with application to nonlinear dynamic gene regulatory network analysis.

作者信息

Lu Tao

机构信息

a Department of Epidemiology and Biostatistics , State University of New York , Rensselaer , New York , USA.

出版信息

J Biopharm Stat. 2016;26(4):712-24. doi: 10.1080/10543406.2015.1052496. Epub 2015 Jun 22.

Abstract

The gene regulation network (GRN) evaluates the interactions between genes and look for models to describe the gene expression behavior. These models have many applications; for instance, by characterizing the gene expression mechanisms that cause certain disorders, it would be possible to target those genes to block the progress of the disease. Many biological processes are driven by nonlinear dynamic GRN. In this article, we propose a nonparametric differential equation (ODE) to model the nonlinear dynamic GRN. Specially, we address following questions simultaneously: (i) extract information from noisy time course gene expression data; (ii) model the nonlinear ODE through a nonparametric smoothing function; (iii) identify the important regulatory gene(s) through a group smoothly clipped absolute deviation (SCAD) approach; (iv) test the robustness of the model against possible shortening of experimental duration. We illustrate the usefulness of the model and associated statistical methods through a simulation and a real application examples.

摘要

基因调控网络(GRN)评估基因之间的相互作用,并寻找描述基因表达行为的模型。这些模型有许多应用;例如,通过表征导致某些疾病的基因表达机制,有可能靶向那些基因以阻止疾病的进展。许多生物过程由非线性动态基因调控网络驱动。在本文中,我们提出了一个非参数微分方程(ODE)来对非线性动态基因调控网络进行建模。特别地,我们同时解决以下问题:(i)从有噪声的时间序列基因表达数据中提取信息;(ii)通过非参数平滑函数对非线性常微分方程进行建模;(iii)通过分组平滑截断绝对偏差(SCAD)方法识别重要的调控基因;(iv)测试模型对实验持续时间可能缩短的稳健性。我们通过一个模拟和一个实际应用示例来说明该模型和相关统计方法的有用性。

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