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首页> 外文期刊>International Journal of Molecular Sciences >Weighted Risk Score-Based Multifactor Dimensionality Reduction to Detect Gene-Gene Interactions in Nasopharyngeal Carcinoma
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Weighted Risk Score-Based Multifactor Dimensionality Reduction to Detect Gene-Gene Interactions in Nasopharyngeal Carcinoma

机译：基于加权风险评分的多因素降维检测鼻咽癌中的基因-基因相互作用

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摘要

Determining the complex relationships between diseases, polymorphisms in human genes and environmental factors is challenging. Multifactor dimensionality reduction (MDR) has been proven to be capable of effectively detecting the statistical patterns of epistasis, although classification accuracy is required for this approach. The imbalanced dataset can cause seriously negative effects on classification accuracy. Moreover, MDR methods cannot quantitatively assess the disease risk of genotype combinations. Hence, we introduce a novel weighted risk score-based multifactor dimensionality reduction (WRSMDR) method that uses the Bayesian posterior probability of polymorphism combinations as a new quantitative measure of disease risk. First, we compared the WRSMDR to the MDR method in simulated datasets. Our results showed that the WRSMDR method had reasonable power to identify high-order gene-gene interactions, and it was more effective than MDR at detecting four-locus models. Moreover, WRSMDR reveals more information regarding the effect of genotype combination on the disease risk, and the result was easier to determine and apply than with MDR. Finally, we applied WRSMDR to a nasopharyngeal carcinoma (NPC) case-control study and identified a statistically significant high-order interaction among three polymorphisms: rs2860580, rs11865086 and rs2305806.
机译：确定疾病，人类基因多态性与环境因素之间的复杂关系具有挑战性。尽管该方法需要分类准确性，但事实证明，多因素降维（MDR）能够有效检测上位性的统计模式。不平衡的数据集可能对分类准确性造成严重的负面影响。此外，MDR方法无法定量评估基因型组合的疾病风险。因此，我们介绍了一种新颖的基于加权风险评分的多因素降维（WRSMDR）方法，该方法将多态性组合的贝叶斯后验概率用作疾病风险的新定量度量。首先，我们在模拟数据集中将WRSMDR与MDR方法进行了比较。我们的结果表明，WRSMDR方法具有确定高阶基因与基因相互作用的合理能力，并且在检测四基因座模型方面比MDR更有效。此外，WRSMDR揭示了更多有关基因型组合对疾病风险影响的信息，并且结果比MDR更容易确定和应用。最后，我们将WRSMDR应用于鼻咽癌（NPC）病例对照研究，并确定了rs2860580，rs11865086和rs2305806这三个多态性之间的统计学上显着的高阶相互作用。

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