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首页> 外文期刊>BMC Genomics >Detecting positive selection from genome scans of linkage disequilibrium
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Detecting positive selection from genome scans of linkage disequilibrium

机译:从连锁不平衡的基因组扫描中检测阳性选择

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Background Though a variety of linkage disequilibrium tests have recently been introduced to measure the signal of recent positive selection, the statistical properties of the various methods have not been directly compared. While most applications of these tests have suggested that positive selection has played an important role in recent human history, the results of these tests have varied dramatically. Results Here, we evaluate the performance of three statistics designed to detect incomplete selective sweeps, LRH and iHS, and ALnLH. To analyze the properties of these tests, we introduce a new computational method that can model complex population histories with migration and changing population sizes to simulate gene trees influenced by recent positive selection. We demonstrate that iHS performs substantially better than the other two statistics, with power of up to 0.74 at the 0.01 level for the variation best suited for full genome scans and a power of over 0.8 at the 0.01 level for the variation best suited for candidate gene tests. The performance of the iHS statistic was robust to complex demographic histories and variable recombination rates. Genome scans involving the other two statistics suffer from low power and high false positive rates, with false discovery rates of up to 0.96 for ALnLH. The difference in performance between iHS and ALnLH, did not result from the properties of the statistics, but instead from the different methods for mitigating the multiple comparison problem inherent in full genome scans. Conclusions We introduce a new method for simulating genealogies influenced by positive selection with complex demographic scenarios. In a power analysis based on this method, iHS outperformed LRH and ALnLH in detecting incomplete selective sweeps. We also show that the single-site iHS statistic is more powerful in a candidate gene test than the multi-site statistic, but that the multi-site statistic maintains a low false discovery rate with only a minor loss of power when applied to a scan of the entire genome. Our results highlight the need for careful consideration of multiple comparison problems when evaluating and interpreting the results of full genome scans for positive selection.
机译:背景技术尽管最近已经引入了各种连锁不平衡测试来测量最近正选择的信号,但是尚未直接比较各种方法的统计特性。这些测试的大多数应用表明,积极选择在最近的人类历史中扮演了重要角色,但这些测试的结果却发生了巨大变化。结果在这里,我们评估了旨在检测​​不完全选择性扫描的三个统计数据的性能:LRH和iHS,以及ALnLH。为了分析这些测试的属性,我们引入了一种新的计算方法,该方法可以模拟具有迁移和不断变化的种群大小的复杂种群历史,以模拟受最近积极选择影响的基因树。我们证明iHS的性能明显优于其他两个统计数据,对于最适合全基因组扫描的变异,iHS在0.01水平上的功效高达0.74,对于最适合候选基因的变异在0.01水平上的功效超过0.8测试。 iHS统计数据的性能对于复杂的人口统计历史和可变的重组率非常可靠。涉及其他两个统计信息的基因组扫描遭受低功耗和高假阳性率的困扰,ALnLH的错误发现率高达0.96。 iHS和ALnLH之间的性能差异不是由统计数据的属性引起的,而是由缓解全基因组扫描固有的多重比较问题的不同方法引起的。结论我们引入了一种新的方法来模拟受正向选择影响的复杂人口统计学家谱。在基于此方法的功率分析中,iHS在检测不完全的选择性扫描方面优于LRH和ALnLH。我们还显示,在候选基因测试中,单站点iHS统计数据比多站点统计数据功能更强大,但是当应用于扫描时,多站点统计数据保持较低的错误发现率,并且只有很小的功耗整个基因组。我们的结果强调,在评估和解释全基因组扫描阳性选择结果时,需要仔细考虑多个比较问题。

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