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Sparse group penalized integrative analysis of multiple cancer prognosis datasets

机译:稀疏组对多种癌症预后数据集的综合惩罚分析

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摘要

In cancer research, high-throughput profiling studies have been extensively conducted, searching for markers associated with prognosis. Owing to the ‘large d, small n’ characteristic, results generated from the analysis of a single dataset can be unsatisfactory. Recent studies have shown that integrative analysis, which simultaneously analyses multiple datasets, can be more effective than single-dataset analysis and classic meta-analysis. In most of existing integrative analysis, the homogeneity model has been assumed, which postulates that different datasets share the same set of markers. Several approaches have been designed to reinforce this assumption. In practice, different datasets may differ in terms of patient selection criteria, profilingtechniques, and many other aspects. Such differences may make the homogeneity model too restricted. In this study, we assume the heterogeneity model, under which different datasets are allowed to have different sets of markers. With multiple cancer prognosis datasets, we adopt the accelerated failure time model to describe survival. This model may have the lowest computational cost among popular semiparametric survival models. For marker selection, we adopt a sparse group minimax concave penalty approach. This approach has an intuitive formulation and can be computed using an effective group coordinate descent algorithm. Simulation study shows that it outperforms the existing approaches under both the homogeneity and heterogeneity models. Data analysis further demonstrates the merit of heterogeneity model and proposed approach.
机译:在癌症研究中,已广泛开展了高通量分析研究,以寻找与预后相关的标志物。由于具有“大d小n”特性,因此对单个数据集进行分析得出的结果可能无法令人满意。最近的研究表明,同时分析多个数据集的集成分析比单数据集分析和经典的元分析更有效。在大多数现有的综合分析中,均采用了同质性模型,该模型假定不同的数据集共享同一组标记。已经设计了几种方法来加强这一假设。在实践中,不同的数据集可能在患者选择标准,配置技术和许多其他方面有所不同。这样的差异可能会使同质性模型受限制。在这项研究中,我们假设采用异质性模型,在该模型下,不同的数据集可以具有不同的标记集。对于多个癌症预后数据集,我们采用加速失败时间模型来描述生存。在流行的半参数生存模型中,该模型的计算成本可能最低。对于标记选择,我们采用稀疏组最小极大凹凹惩罚方法。这种方法具有直观的公式,可以使用有效的组坐标下降算法进行计算。仿真研究表明,它在同质性和异质性模型下均优于现有方法。数据分析进一步证明了异构模型的优点和提出的方法。

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