用于分子癌症诊断和预后的相对表达分析。

Relative expression analysis for molecular cancer diagnosis and prognosis.

机构信息

Institute for Genomic Biology, University of Illinois, Urbana, IL 61801, USA.

出版信息

Technol Cancer Res Treat. 2010 Apr;9(2):149-59. doi: 10.1177/153303461000900204.

Abstract

The enormous amount of biomolecule measurement data generated from high-throughput technologies has brought an increased need for computational tools in biological analyses. Such tools can enhance our understanding of human health and genetic diseases, such as cancer, by accurately classifying phenotypes, detecting the presence of disease, discriminating among cancer sub-types, predicting clinical outcomes, and characterizing disease progression. In the case of gene expression microarray data, standard statistical learning methods have been used to identify classifiers that can accurately distinguish disease phenotypes. However, these mathematical prediction rules are often highly complex, and they lack the convenience and simplicity desired for extracting underlying biological meaning or transitioning into the clinic. In this review, we survey a powerful collection of computational methods for analyzing transcriptomic microarray data that address these limitations. Relative Expression Analysis (RXA) is based only on the relative orderings among the expressions of a small number of genes. Specifically, we provide a description of the first and simplest example of RXA, the K-TSP classifier, which is based on _ pairs of genes; the case K = 1 is the TSP classifier. Given their simplicity and ease of biological interpretation, as well as their invariance to data normalization and parameter-fitting, these classifiers have been widely applied in aiding molecular diagnostics in a broad range of human cancers. We review several studies which demonstrate accurate classification of disease phenotypes (e.g., cancer vs. normal), cancer subclasses (e.g., AML vs. ALL, GIST vs. LMS), disease outcomes (e.g., metastasis, survival), and diverse human pathologies assayed through blood-borne leukocytes. The studies presented demonstrate that RXA-specifically the TSP and K-TSP classifiers-is a promising new class of computational methods for analyzing high-throughput data, and has the potential to significantly contribute to molecular cancer diagnosis and prognosis.

摘要

从高通量技术生成的大量生物分子测量数据使得在生物分析中对计算工具的需求增加。这些工具可以通过准确地对表型进行分类、检测疾病的存在、区分癌症亚型、预测临床结果和描述疾病进展,来增强我们对人类健康和遗传疾病(如癌症)的理解。在基因表达微阵列数据的情况下,已经使用标准统计学习方法来识别可以准确区分疾病表型的分类器。然而,这些数学预测规则通常非常复杂,缺乏提取潜在生物学意义或转化为临床应用所需的便利性和简单性。在这篇综述中,我们调查了一组用于分析转录组微阵列数据的强大计算方法,以解决这些限制。相对表达分析(RXA)仅基于少数基因表达的相对顺序。具体来说,我们提供了 RXA 的第一个也是最简单的例子,即 K-TSP 分类器的描述,该分类器基于 _对基因;K = 1 的情况是 TSP 分类器。鉴于它们的简单性和易于生物学解释,以及它们对数据归一化和参数拟合的不变性,这些分类器已广泛应用于辅助广泛的人类癌症中的分子诊断。我们回顾了几项研究,这些研究证明了疾病表型(例如癌症与正常)、癌症亚型(例如 AML 与 ALL、GIST 与 LMS)、疾病结果(例如转移、生存)以及通过血液白细胞检测到的各种人类病理学的准确分类。提出的研究表明,RXA-特别是 TSP 和 K-TSP 分类器-是分析高通量数据的一类有前途的新计算方法,有可能为分子癌症诊断和预后做出重大贡献。

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