Detection of gene pathways with predictive power for breast cancer prognosis.
Detection of gene pathways with predictive power for breast cancer prognosis.
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DOI：
10.1186/1471-2105-11-1
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发表时间：
2010-01-01
影响因子：
3
通讯作者：
Kosorok MR
中科院分区：
文献类型：
--
作者：
Ma S;Kosorok MR
预后对于乳腺癌研究至关重要。生物医学研究表明，基因组测量可能对预后具有独立的预测能力。已经进行了基因分析研究来寻找预测基因组测量值。基因具有固有的通路结构，通路由多个功能协调的基因组成。本研究的目的是确定对乳腺癌预后具有预测能力的基因途径。由于我们的目标与现有研究的目标根本不同，因此提出了一种新的路径分析方法。新方法在以下方面超越了现有的替代方法。首先，它可以评估基因通路的预测能力，而现有方法往往只关注模型拟合的准确性。其次，它可以解释通路中多个基因的联合效应，而现有方法往往关注基因的边际效应。第三，它可以容纳多个异构数据集，而现有方法仅分析单个数据集。我们分析了四项乳腺癌预后研究，并确定了 97 条对预后具有显着预测能力的途径。确定了替代方法错过的重要途径。所提出的方法为现有路径分析方法提供了一种有用的替代方法。确定的途径可以为乳腺癌预后提供进一步的见解。
Prognosis is of critical interest in breast cancer research. Biomedical studies suggest that genomic measurements may have independent predictive power for prognosis. Gene profiling studies have been conducted to search for predictive genomic measurements. Genes have the inherent pathway structure, where pathways are composed of multiple genes with coordinated functions. The goal of this study is to identify gene pathways with predictive power for breast cancer prognosis. Since our goal is fundamentally different from that of existing studies, a new pathway analysis method is proposed. The new method advances beyond existing alternatives along the following aspects. First, it can assess the predictive power of gene pathways, whereas existing methods tend to focus on model fitting accuracy only. Second, it can account for the joint effects of multiple genes in a pathway, whereas existing methods tend to focus on the marginal effects of genes. Third, it can accommodate multiple heterogeneous datasets, whereas existing methods analyze a single dataset only. We analyze four breast cancer prognosis studies and identify 97 pathways with significant predictive power for prognosis. Important pathways missed by alternative methods are identified. The proposed method provides a useful alternative to existing pathway analysis methods. Identified pathways can provide further insights into breast cancer prognosis.
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