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首页> 外文期刊>Computational Biology and Bioinformatics, IEEE/ACM Transactions on >Statistical Detection of Intrinsically Multivariate Predictive Genes
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Statistical Detection of Intrinsically Multivariate Predictive Genes

机译：本征多元预测基因的统计检测

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摘要

Canalizing genes possess broad regulatory power over a wide swath of regulatory processes. On the other hand, it has been hypothesized that the phenomenon of intrinsically multivariate prediction (IMP) is associated with canalization. However, applications have relied on user-selectable thresholds on the IMP score to decide on the presence of IMP. A methodology is developed here that avoids arbitrary thresholds, by providing a statistical test for the IMP score. In addition, the proposed procedure allows the incorporation of prior knowledge if available, which can alleviate the problem of loss of power due to small sample sizes. The issue of multiplicity of tests is addressed by family-wise error rate (FWER) and false discovery rate (FDR) controlling approaches. The proposed methodology is demonstrated by experiments using synthetic and real gene-expression data from studies on melanoma and ionizing radiation (IR) responsive genes. The results with the real data identified DUSP1 and p53, two well-known canalizing genes associated with melanoma and IR response, respectively, as the genes with a clear majority of IMP predictor pairs. This validates the potential of the proposed methodology as a tool for discovery of canalizing genes from binary gene-expression data. The procedure is made available through an R package.
机译：运河化基因在广泛的调控过程中具有广泛的调控能力。另一方面，已经假设本质上的多变量预测（IMP）现象与渠化相关。但是，应用程序依赖于IMP得分的用户可选阈值来确定IMP的存在。通过提供针对IMP得分的统计测试，这里开发了一种避免任意阈值的方法。另外，所提议的程序允许在可能的情况下并入现有知识，这可以减轻由于小样本量导致的功率损失的问题。测试的多重性问题通过控制家庭错误率（FWER）和错误发现率（FDR）来解决。通过使用来自黑色素瘤和电离辐射（IR）响应基因研究的合成和真实基因表达数据进行的实验，证明了所提出的方法。真实数据的结果将DUSP1和p53，这两个与黑色素瘤和IR反应相关的众所周知的运河化基因分别确定为具有大部分IMP预测因子对的基因。这验证了所提出的方法学作为从二进制基因表达数据中发现渠化基因的工具的潜力。该过程可通过R软件包获得。

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