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利用基因表达谱和状态空间模型对T细胞活化进行建模。

Modeling T-cell activation using gene expression profiling and state-space models.

作者信息

Rangel Claudia, Angus John, Ghahramani Zoubin, Lioumi Maria, Sotheran Elizabeth, Gaiba Alessia, Wild David L, Falciani Francesco

机构信息

School of Mathematical Sciences, Claremont Graduate University, 121 E. Tenth St., Claremont, CA 91711, USA.

出版信息

Bioinformatics. 2004 Jun 12;20(9):1361-72. doi: 10.1093/bioinformatics/bth093. Epub 2004 Feb 12.


DOI:10.1093/bioinformatics/bth093
PMID:14962938
Abstract

MOTIVATION: We have used state-space models to reverse engineer transcriptional networks from highly replicated gene expression profiling time series data obtained from a well-established model of T-cell activation. State space models are a class of dynamic Bayesian networks that assume that the observed measurements depend on some hidden state variables that evolve according to Markovian dynamics. These hidden variables can capture effects that cannot be measured in a gene expression profiling experiment, e.g. genes that have not been included in the microarray, levels of regulatory proteins, the effects of messenger RNA and protein degradation, etc. RESULTS: Bootstrap confidence intervals are developed for parameters representing 'gene-gene' interactions over time. Our models represent the dynamics of T-cell activation and provide a methodology for the development of rational and experimentally testable hypotheses. AVAILABILITY: Supplementary data and Matlab computer source code will be made available on the web at the URL given below. SUPPLEMENTARY INFORMATION: http://public.kgi.edu/~wild/LDS/index.htm

摘要

动机:我们已使用状态空间模型,从通过成熟的T细胞激活模型获得的高度重复的基因表达谱时间序列数据中反向构建转录网络。状态空间模型是一类动态贝叶斯网络,其假定观测到的测量值取决于一些根据马尔可夫动力学演化的隐藏状态变量。这些隐藏变量可以捕捉在基因表达谱实验中无法测量的效应,例如未包含在微阵列中的基因、调节蛋白的水平、信使RNA和蛋白质降解的效应等。 结果:为表示随时间变化的“基因-基因”相互作用的参数建立了自举置信区间。我们的模型代表了T细胞激活的动态过程,并为合理且可通过实验检验的假设的提出提供了一种方法。 可用性:补充数据和Matlab计算机源代码将在以下给定的网址在网上提供。 补充信息:http://public.kgi.edu/~wild/LDS/index.htm

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