An efficient and robust statistical modeling approach to discover differentially expressed genes using genomic expression profiles
An efficient and robust statistical modeling approach to discover differentially expressed genes using genomic expression profiles
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DOI：
10.1101/gr.165101
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发表时间：
2001-07-01
期刊：
影响因子：
7
通讯作者：
Zhao, LP
中科院分区：
文献类型：
--
作者：
Thomas, JG;Olson, JM;Zhao, LP
我们开发了一种统计回归建模方法来发现在DNA微阵列实验中两个预定义样本组之间差异表达的基因。我们的模型基于定义明确的假设，使用了严格和特征明确的统计方法，并考虑了数据的异质性和基因组复杂性。与试图定义共享共同整体表达谱的基因组和/或样本的聚类分析不同，我们的建模方法使用已知的样本组成员资格，以敏感和稳健的方式关注单个基因的表达谱。此外，这种方法可以用来检验关于基因表达的统计假设。为了证明这一方法学，我们比较了11例急性髓系白血病(AML)和27例急性淋巴细胞白血病(ALL)样本的表达谱。1999年)ACID发现141个基因在AML和ALL之间有差异表达，在基因组水平上有1%的意义。使用这种建模方法对AML样本中的不同样本组进行比较，我们发现了一组其表达谱与血小板生成素相关的基因，并发现其表达与AML治疗结果相关的基因位于重复的染色体位置。我们的结果与使用t检验或Wilcoxon秩和统计量得到的结果进行了比较。
We have developed a statistical regression modeling approach to discover genes that are differentially expressed between two predefined sample groups in DNA microarray experiments. Our model is based on well-defined assumptions, uses rigorous and well-characterized statistical measures, and accounts for the heterogeneity and genomic complexity of the data. In contrast to cluster analysis, which attempts to define groups of genes and/or samples that share common overall expression profiles, our modeling approach uses known sample group membership to Focus on expression profiles of individual genes in a sensitive and robust manner. Further, this approach can be used to test statistical hypotheses about gene expression. To demonstrate this methodology, we compared the expression profiles of 11 acute myeloid leukemia (AML) and 27 acute lymphoblastic leukemia (ALL) samples From a previous study (Golub et al. 1999) acid found 141 genes differentially expressed between AML and ALL with a 1% significance at the genomic level. Using this modeling approach to compare different sample groups within the AML samples, we identified a group of genes whose expression profiles correlated with that of thrombopoietin and found that genes whose expression associated with AML treatment outcome lie in recurrent chromosomal locations. Our results are compared with those obtained using t-tests or Wilcoxon rank sum statistics.