Statistical Methods for Normalizing Microarrays in Cancer Biomarker Studies

描述（由申请人提供）：已经开发了用于基因表达微阵列的各种阵列标准化方法。这些方法大多假设样本组之间的差异表达很少或对称。目前还没有对这些方法在利用异质性样品（如肿瘤）标准化microRNA表达阵列中的特性进行系统研究。microRNA阵列仅包含几百个microRNA，并且可能在不同的肿瘤组之间具有相对大的比例差异表达。在这种情况下，评估标准化方法是困难的，因为缺乏一个基准数据集，没有混淆数组的影响。我们建议设计和生成这样的基准数据集，进行归一化方法的系统评估，特别强调这些模型用于检测具有差异表达的标志物的实用性，并从基准数据设计中导出承认肿瘤样本固有的异质性的统计模型。 公共卫生相关性：微阵列被广泛用于癌症研究。处理微阵列数据的一个关键步骤是将阵列标准化，以便不同阵列的测量结果具有可比性。有一个很大的需要，以评估阵列归一化的统计方法的属性时，他们被应用到microRNA阵列利用异质性样品，如肿瘤。

DESCRIPTION (provided by applicant): Various array normalization methods have been developed for gene expression microarrays. Most of these methods assume few or symmetric differential expression between sample groups. There has been no systematic study of the properties of these methods in normalizing microRNA expression arrays utilizing heterogeneous samples such as tumors. MicroRNA arrays contain only a few hundred microRNAs, and are likely to have a relatively large proportion being differentially expressed between diverse tumor groups. The assessment of normalization methods in this setting is difficult because of the lack of a benchmark dataset that has no confounding array effects. We propose to design and generate such benchmark datasets, perform a systematic assessment of normalization methods with a particular emphasis on the utility of these models for detecting markers with differential expression, and from the benchmark data design derive statistical models that acknowledge heterogeneities inherent to tumor samples. PUBLIC HEALTH RELEVANCE: Microarrays are being widely used in cancer research. A critical step for processing microarray data is to normalize the arrays so that measurements from different arrays are comparable. There is a great need to evaluate the properties of statistical methods for array normalization when they are applied to microRNA arrays utilizing heterogeneous samples such as tumors.