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arXiv 1802.08178stat.ME
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高维变量选择的相关调整回归生存分数

Correlation-Adjusted Regression Survival Scores for High-Dimensional Variable Selection

Thomas Welchowski, Verena Zuber, Matthias Schmid

摘要:

背景资料:个性化医疗分类方法的发展高度依赖于预测性遗传标记的鉴定。在生存分析中,经常需要区分有影响和无影响的标志物。通常,第一步是执行单变量筛选步骤,根据标记物与结果的关联对标记物进行排名。通常使用Cox评分进行筛选,Cox评分量化了生存与每个标记物之间的关联。由于Cox评分不考虑标记物之间的依赖性,因此在存在高度相关的标记物的情况下,它们的使用是次优的。研究方法:作为Cox评分的替代,我们提出了右删失生存结局的相关调整回归生存(CARS)评分。通过去除标志物之间的相关性,CARS评分量化了结果与“去相关”标志物值集之间的关联。分数的估计基于逆概率加权,其应用于对数转换的事件时间。对于高维数据,估计是基于收缩技术。结果:在轻度正则条件下,CARS评分具有一致性。在模拟中,基于CARS分数排名的生存模型比竞争方法获得了更高的精确度-召回率曲线下的面积。在前列腺癌和乳腺癌上的两个示例应用证实了这些结果。CARS评分在R软件包carSurv中实现。结论:在涉及高维遗传数据的研究应用中,即使协变量之间的相关性较低,使用CARS评分进行标记选择也是Cox评分的有利替代方案。CARS评分具有简单的解释和低计算要求,是个性化医学研究中易于使用的筛选工具。

英文摘要:

Background: The development of classification methods for personalized medicine is highly dependent on the identification of predictive genetic markers. In survival analysis it is often necessary to discriminate between influential and non-influential markers. Usually, the first step is to perform a univariate screening step that ranks the markers according to their associations with the outcome. It is common to perform screening using Cox scores, which quantify the associations between survival and each of the markers individually. Since Cox scores do not account for dependencies between the markers, their use is suboptimal in the presence highly correlated markers. Methods: As an alternative to the Cox score, we propose the correlation-adjusted regression survival (CARS) score for right-censored survival outcomes. By removing the correlations between the markers, the CARS score quantifies the associations between the outcome and the set of "de-correlated" marker values. Estimation of the scores is based on inverse probability weighting, which is applied to log-transformed event times. For high-dimensional data, estimation is based on shrinkage techniques. Results: The consistency of the CARS score is proven under mild regularity conditions. In simulations, survival models based on CARS score rankings achieved higher areas under the precision-recall curve than competing methods. Two example applications on prostate and breast cancer confirmed these results. CARS scores are implemented in the R package carSurv. Conclusions: In research applications involving high-dimensional genetic data, the use of CARS scores for marker selection is a favorable alternative to Cox scores even when correlations between covariates are low. Having a straightforward interpretation and low computational requirements, CARS scores are an easy-to-use screening tool in personalized medicine research.

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