Robustness of coalescent estimators to between-lineage mutation rate variation.
Robustness of coalescent estimators to between-lineage mutation rate variation.
复制标题
合并估计器对谱系间突变率变化的鲁棒性。
DOI：
10.1093/molbev/msl106
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发表时间：
2006
影响因子：
10.7
通讯作者：
Kuhner,MaryK
中科院分区：
文献类型：
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作者：
Kuhner,MaryK
来自HIV和人类肿瘤细胞的数据可以显示即使在单个群体内也存在大量谱系间突变率差异。这种变化可能会影响人口数量的估计，如Θ = 4 Ne μ。使用模拟的DNA数据，我通过Watterson（Watterson GA. 1975.无重组遗传系统中分离位点的数目。7：256-276）和聚结最大似然算法LAMARC（Kuhner MK. 2006. LAMARC 2.0：总体参数的最大似然和贝叶斯估计。生物信息学。Advance Access doi：10.1093/bioinformatics/btk051）。Watterson的估计值显示出向下的偏差，正如预期的那样，具有高的Θ值。LAMARC的平均估计值对于所有测试的θ值和速率变化都是准确的，除了速率变化最大时的向下偏差（即，慢速率为零）。LAMARC的置信区间（CI）始终比Watterson估计值窄。两种方法往往拒绝真理太频繁时，速率变化是8倍或更大，独立的分支，以及当变化是4倍或更大，分支之间的相关性。在沃特森的估计的情况下，这种过度拒绝完全归因于与快速和慢速相关的总分支长度的系谱之间的变化。然而，在LAMARC的情况下，仍然观察到一些过度排斥反应，即使考虑到系谱之间的变化。这两种估计量对适度的速率变化都是稳健的;但是，它们的使用应与统计检验相结合，以排除极端速率变化，因为所得CI可能不可靠。
Data from HIV and from human neoplastic cells can show substantial between-lineage mutation rate variation even within a single population. Such variation may affect estimators of population quantities such as Θ = 4Neμ. Using simulated DNA data, I measured the effect of rate variation on recovery of Θ by the summary-statistic estimator of Watterson (Watterson GA. 1975. On the number of segregating sites in genetical systems without recombination. Theor Popul Biol. 7:256–276) and the coalescent maximum likelihood algorithm LAMARC (Kuhner MK. 2006. LAMARC 2.0: maximum likelihood and Bayesian estimation of population parameters. Bioinformatics. Advance Access doi: 10.1093/bioinformatics/btk051). Watterson's estimator showed a downward bias, as expected, with high values of Θ. LAMARC's mean estimate was accurate for all tested values of Θ and rate variation except for a downward bias when rate variation was maximal (i.e., the slow rate was zero). LAMARC had consistently narrower confidence intervals (CIs) than Watterson's estimator. Both methods tended to reject the truth too often when rate variation was 8x or greater and independent among branches, as well as when variation was 4x or greater and correlated among branches. In the case of Watterson's estimate, this excess rejection was fully attributable to variation among genealogies in the amount of total branch length associated with the fast and slow rates. However, in the case of LAMARC, some excess rejection was still observed even when between-genealogy variation was taken into account. Both estimators are robust to modest rate variation; however, their use should be coupled with a statistical test to rule out extreme rate variation as the resulting CIs may not be reliable.