Tests for finding complex patterns of differential expression in cancers: towards individualized medicine.
Tests for finding complex patterns of differential expression in cancers: towards individualized medicine.
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DOI：
10.1186/1471-2105-5-110
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发表时间：
2004-08-12
影响因子：
3
通讯作者：
Godfrey TE
中科院分区：
文献类型：
--
作者：
Lyons-Weiler J;Patel S;Becich MJ;Godfrey TE
癌症中的微阵列研究比较了两个或多个样本组之间数千个基因的表达水平。数据分析遵循人口水平方法（例如，样品平均值的比较）以鉴定差异表达的基因。这导致了“群体水平”标记的发现，即，具有表达模式A > B和B > A的基因。我们介绍了PPST测试，确定基因的情况下，一个显着的大子集表现出的表达值超出了上限和下限的阈值在对照样品中观察到的。有趣的是，该测试鉴定了被群体水平方法（例如t检验）遗漏的A > B和B < A模式基因，以及在统计学上显著大的癌症患者子集中表现出显著过表达和显著低表达的许多基因（阿坝模式基因）。这些模式倾向于显示单个基因特有的分布，并且在“基因表达模式网格”中适当地可视化。在这些基因中的低程度的基因相关性表明独特的潜在的基因组病理学和高度的独特的肿瘤特异性差异表达。我们通过分析两个独立发表的星形细胞瘤进展研究数据集，将PPST和阿坝检验与参数和非参数t检验进行比较。PPST检验的结果与非参数t检验相似，具有更高的自我一致性。这些测试和基因表达模式网格可用于鉴定仅存在于癌症患者亚组中的治疗靶点和诊断或预后标记物，并提供癌症差异表达的更完整的描述。
Microarray studies in cancer compare expression levels between two or more sample groups on thousands of genes. Data analysis follows a population-level approach (e.g., comparison of sample means) to identify differentially expressed genes. This leads to the discovery of 'population-level' markers, i.e., genes with the expression patterns A > B and B > A. We introduce the PPST test that identifies genes where a significantly large subset of cases exhibit expression values beyond upper and lower thresholds observed in the control samples. Interestingly, the test identifies A > B and B < A pattern genes that are missed by population-level approaches, such as the t-test, and many genes that exhibit both significant overexpression and significant underexpression in statistically significantly large subsets of cancer patients (ABA pattern genes). These patterns tend to show distributions that are unique to individual genes, and are aptly visualized in a 'gene expression pattern grid'. The low degree of among-gene correlations in these genes suggests unique underlying genomic pathologies and high degree of unique tumor-specific differential expression. We compare the PPST and the ABA test to the parametric and non-parametric t-test by analyzing two independently published data sets from studies of progression in astrocytoma. The PPST test resulted findings similar to the nonparametric t-test with higher self-consistency. These tests and the gene expression pattern grid may be useful for the identification of therapeutic targets and diagnostic or prognostic markers that are present only in subsets of cancer patients, and provide a more complete portrait of differential expression in cancer.
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DOI：
10.1073/pnas.011404098
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
影响因子：
56.9
作者：
Golub, TR;Slonim, DK;Lander, ES
通讯作者：
Lander, ES
影响因子：
8
作者：
De Vos, J;Thykjær, T;Klein, B
通讯作者：
Klein, B
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
5.8
作者：
Baldi, P;Long, AD
通讯作者：
Long, AD