An enhanced quantile approach for assessing differential gene expressions

An enhanced quantile approach for assessing differential gene expressions
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DOI:
10.1111/j.1541-0420.2007.00903.x
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发表时间:
2008-06-01
期刊:
影响因子:
1.9
通讯作者:
He, Xuming
He, Xuming
中科院分区:
数学3区
文献类型:
--
作者:
Wang, Huixia;He, Xuming

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由于在典型的基因微阵列实验中重复的次数很少,如果没有某种形式的跨基因信息共享,统计推断的性能往往不令人满意。在本文中,我们提出了一种增强分位数秩评分检验(EQRS),通过探针水平测量分析基因强度分布的分位数,用于检测基因芯片研究中的差异表达。符号相关的度量,delta,在等级分数检验中起着重要的作用。通过共享基因间的信息,我们开发了delta的校准估计,这减少了小样本量下的可变性。我们将EQRS测试与其他四种确定差异表达的方法进行了比较:基因特异性分位数秩评分测试,假设共同delta的分位数秩评分测试,使用汇总探针集水平强度的改进t检验,以及探针水平数据的Mack-Skillings秩检验。所提出的EQRS被证明有利于保持错误发现率和对外围阵列的鲁棒性。此外,我们通过一项基因芯片研究,比较暴露于慢性间歇性缺氧和暴露于间歇性室内空气的小鼠肝脏中的基因表达,证明了该方法的优点。
Due to the small number of replicates in typical gene microarray experiments, the performance of statistical inference is often unsatisfactory without some form of information-sharing across genes. In this article, we propose an enhanced quantile rank score test (EQRS) for detecting differential expression in GeneChip studies by analyzing the quantiles of gene intensity distributions through probe-level measurements. A measure of sign correlation, delta, plays an important role in the rank score tests. By sharing information across genes, we develop a calibrated estimate of delta, which reduces the variability at small sample sizes. We compare the EQRS test with four other approaches for determining differential expression: the gene-specific quantile rank score test, the quantile rank score test assuming a common delta, a modified t-test using summarized probe-set-level intensities, and the Mack-Skillings rank test on probe-level data. The proposed EQRS is shown to be favorable for preserving false discovery rates and for being robust against outlying arrays. In addition, we demonstrate the merits of the proposed approach using a GeneChip study comparing gene expression in the livers of mice exposed to chronic intermittent hypoxia and of those exposed to intermittent room air.