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Improved confidence intervals in quantitative trait loci mapping by permutation bootstrapping.

机译:通过置换自举提高了定量性状基因座映射的置信区间。

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摘要

The nonparametric bootstrap approach is known to be suitable for calculating central confidence intervals for the locations of quantitative trait loci (QTL). However, the distribution of the bootstrap QTL position estimates along the chromosome is peaked at the positions of the markers and is not tailed equally. This results in conservativeness and large width of the confidence intervals. In this study three modified methods are proposed to calculate nonparametric bootstrap confidence intervals for QTL locations, which compute noncentral confidence intervals (uncorrected method I), correct for the impact of the markers (weighted method I), or both (weighted method II). Noncentral confidence intervals were computed with an analog of the highest posterior density method. The correction for the markers is based on the distribution of QTL estimates along the chromosome when the QTL is not linked with any marker, and it can be obtained with a permutation approach. In a simulation study the three methods were compared with the original bootstrap method. The results showed that it is useful, first, to compute noncentral confidence intervals and, second, to correct the bootstrap distribution of the QTL estimates for the impact of the markers. The weighted method II, combining these two properties, produced the shortest and less biased confidence intervals in a large number of simulated configurations.
机译:已知非参数自举方法适用于计算定量性状基因座(QTL)位置的中心置信区间。但是,引导程序QTL位置估计沿染色体的分布在标记的位置达到峰值,并且尾部分布不均。这导致保守性和较大的置信区间宽度。在这项研究中,提出了三种修改的方法来计算QTL位置的非参数自举置信区间,该方法计算非中心置信区间(未校正的方法I),校正标记的影响(加权的方法I)或两者(加权的方法II)。使用最高后验密度法的类似物计算非中心置信区间。当QTL不与任何标记关联时,标记的校正基于QTL估计值在染色体上的分布,可以通过置换方法获得。在模拟研究中,将这三种方法与原始引导方法进行了比较。结果表明,首先,要计算非中心置信区间,其次,对于标记的影响,校正QTL估计的自举分布是有用的。结合这两个属性的加权方法II在大量模拟配置中产生了最短且偏差较小的置信区间。

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