A robust method for estimating gene expression states using Affymetrix microarray probe level data.

A robust method for estimating gene expression states using Affymetrix microarray probe level data.
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DOI:
10.1186/1471-2105-11-183
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发表时间:
2010-04-12
期刊:
影响因子:
3
通讯作者:
Hiyama E
Hiyama E
中科院分区:
生物学4区
文献类型:
--
作者:
Ohtaki M;Otani K;Hiyama K;Kamei N;Satoh K;Hiyama E

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微阵列技术是一种高通量的方法,可以同时检测上千个基因的表达水平。观察到的强度结合了联合收割机的非特异性结合,这是微阵列数据的主要缺点。AffytechnologyGeneChip分配了一个错配(MM)探针,目的是测量非特异性结合,但关于MM测量的有用性存在各种意见。应该注意的是,并非所有观察到的强度都与表达的基因相关,并且其中许多与未表达的基因相关,其中测量值仅表示由于非特异性结合、交叉杂交或杂散信号而产生的噪声。所有基因都表达的隐含假设导致微阵列数据分析的性能不佳。我们假设一个基因的两个功能状态-表达或未表达-并提出了一个强大的方法来估计基因表达状态使用PM和MM措施之间的顺序关系。使用探针组内的探针对的数量获得指标“基因表达的概率”,其中PM测量超过MM测量。我们使用Affytechnology提供的人类基因组U95数据集检查了所提出的指标的有效性。通过探索参与神经母细胞瘤预后的候选基因来说明“基因表达概率”的有用性。我们确定了候选基因的表达状态不同(未表达或表达)时,比较两个结果。随后通过定量RT-PCR证实了该结果的有效性。提出的定性评价,“基因表达的概率”,是一个有用的指标,提高微阵列数据分析。这有助于减少错误发现的数量。表达状态-表达或未表达-对应于最基本的基因功能“开”和“关”,这可以导致生物学上有意义的结果。
Microarray technology is a high-throughput method for measuring the expression levels of thousand of genes simultaneously. The observed intensities combine a non-specific binding, which is a major disadvantage with microarray data. The Affymetrix GeneChip assigned a mismatch (MM) probe with the intention of measuring non-specific binding, but various opinions exist regarding usefulness of MM measures. It should be noted that not all observed intensities are associated with expressed genes and many of those are associated with unexpressed genes, of which measured values express mere noise due to non-specific binding, cross-hybridization, or stray signals. The implicit assumption that all genes are expressed leads to poor performance of microarray data analyses. We assume two functional states of a gene - expressed or unexpressed - and propose a robust method to estimate gene expression states using an order relationship between PM and MM measures. An indicator 'probability of a gene being expressed' was obtained using the number of probe pairs within a probe set where the PM measure exceeds the MM measure. We examined the validity of the proposed indicator using Human Genome U95 data sets provided by Affymetrix. The usefulness of 'probability of a gene being expressed' is illustrated through an exploration of candidate genes involved in neuroblastoma prognosis. We identified the candidate genes for which expression states differed (un-expressed or expressed) when compared between two outcomes. The validity of this result was subsequently confirmed by quantitative RT-PCR. The proposed qualitative evaluation, 'probability of a gene being expressed', is a useful indicator for improving microarray data analysis. It is useful to reduce the number of false discoveries. Expression states - expressed or unexpressed - correspond to the most fundamental gene function 'On' and 'Off', which can lead to biologically meaningful results.
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发表时间: 2001-01-02
影响因子: 11.1
作者:
Li, C;Wong, WH
通讯作者: Wong, WH
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发表时间: 2006-01-31
期刊: BMC BIOINFORMATICS
影响因子: 3
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DOI: 10.1073/pnas.091062498
发表时间: 2001-04-24
影响因子: 11.1
作者:
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通讯作者: Chu, G
DOI: 10.1093/bioinformatics/18.12.1585
发表时间: 2002-12-01
期刊: BIOINFORMATICS
影响因子: 5.8
作者:
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