Pathway level analysis of gene expression using singular value decomposition.
Pathway level analysis of gene expression using singular value decomposition.
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DOI：
10.1186/1471-2105-6-225
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发表时间：
2005-09-12
影响因子：
3
通讯作者：
Kepler TB
中科院分区：
文献类型：
--
作者：
Tomfohr J;Lu J;Kepler TB
基因表达分析的一个有希望的方向集中在预先已知相关的特定预定义基因组的表达变化（例如，编码参与细胞途径或复合物的蛋白质的基因）。这样的分析可以揭示从单个基因的变异中不容易看到的特征，并可以导致生物学上更透明和更容易解释的表达图片。在这篇文章中，我们提出了一种新的方法，这种方法通过量化不同样品中每种途径的“活性”水平来操作。从奇异值分解得出的活动水平构成了统计比较和其他应用的基础。我们使用来自2型糖尿病研究的表达数据和香烟烟雾对气道上皮细胞基因表达的影响的另一项研究来证明我们的方法。在吸烟者和非吸烟者之间的比较中确定了许多有趣的途径，包括与尼古丁代谢、粘液产生和谷胱甘肽代谢相关的途径。与相关的方法，“基因集富集分析”的结果进行比较，也提供了。我们的方法提供了一个灵活的基础，从基因表达数据中识别差异表达的途径。基于路径的分析的结果可以与从更专注于单个基因的分析中获得的结果互补。用于进行本文所述分析的网络程序PLAGE（基因表达的途径水平分析）可访问。
A promising direction in the analysis of gene expression focuses on the changes in expression of specific predefined sets of genes that are known in advance to be related (e.g., genes coding for proteins involved in cellular pathways or complexes). Such an analysis can reveal features that are not easily visible from the variations in the individual genes and can lead to a picture of expression that is more biologically transparent and accessible to interpretation. In this article, we present a new method of this kind that operates by quantifying the level of 'activity' of each pathway in different samples. The activity levels, which are derived from singular value decompositions, form the basis for statistical comparisons and other applications. We demonstrate our approach using expression data from a study of type 2 diabetes and another of the influence of cigarette smoke on gene expression in airway epithelia. A number of interesting pathways are identified in comparisons between smokers and non-smokers including ones related to nicotine metabolism, mucus production, and glutathione metabolism. A comparison with results from the related approach, 'gene-set enrichment analysis', is also provided. Our method offers a flexible basis for identifying differentially expressed pathways from gene expression data. The results of a pathway-based analysis can be complementary to those obtained from one more focused on individual genes. A web program PLAGE (Pathway Level Analysis of Gene Expression) for performing the kinds of analyses described here is accessible at .
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DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G
DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
Alter, O;Brown, PO;Botstein, D
通讯作者：
Botstein, D
影响因子：
5.8
作者：
Baldi, P;Long, AD
通讯作者：
Long, AD
DOI：
10.1198/016214501753382129
发表时间：
2001-12-01
影响因子：
3.7
作者：
Efron, B;Tibshirani, R;Tusher, V
通讯作者：
Tusher, V
影响因子：
12.3
作者：
Doniger SW;Salomonis N;Dahlquist KD;Vranizan K;Lawlor SC;Conklin BR
通讯作者：
Conklin BR