Differential expression in SAGE: accounting for normal between-library variation

Differential expression in SAGE: accounting for normal between-library variation
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DOI:
10.1093/bioinformatics/btg173
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发表时间:
2003-08-12
期刊:
影响因子:
5.8
通讯作者:
Aldaz, CM
Aldaz, CM
中科院分区:
生物学3区
文献类型:
--
作者:
Baggerly, KA;Deng, L;Aldaz, CM

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动机:在对比SAGE文库组之间的基因表达水平时,通常将每组内的文库合并,并将感兴趣的标签的计数相加,并基于这些较大的“假文库”进行推断。虽然这捕获了程序中固有的采样可变性,但它未能考虑到同一组内个体之间基因水平的正常变化,因此可能夸大结果的意义。影响并不轻微:库间变异可能是库内变异的数百倍。结果:我们引入了一个β-二项式抽样模型,正确地将两个来源的变化。我们展示了如何拟合这个模型的参数,并引入了一个类似于双样本t检验的差异表达的检验统计量。
Motivation: In contrasting levels of gene expression between groups of SAGE libraries, the libraries within each group are often combined and the counts for the tag of interest summed, and inference is made on the basis of these larger 'pseudolibraries'. While this captures the sampling variability inherent in the procedure, it fails to allow for normal variation in levels of the gene between individuals within the same group, and can consequently overstate the significance of the results. The effect is not slight: between-library variation can be hundreds of times the within-library variation.Results: We introduce a beta-binomial sampling model that correctly incorporates both sources of variation. We show how to fit the parameters of this model, and introduce a test statistic for differential expression similar to a two-sample t-test.