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Haplotype Allele Frequency (HAF) Score: Predicting Carriers of Ongoing Selective Sweeps Without Knowledge of the Adaptive Allele

机译:单倍型等位基因频率(HAF)得分:预测正在进行的选择性扫描的携带者,而无需了解自适应等位基因

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Methods for detecting the genomic signatures of natural selection are heavily studied, and have been successful in identifying many selective sweeps. For the vast majority of these sweeps the adaptive allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. Because carriers of ongoing selective sweeps are likely to contain a future most recent common ancestor, identifying them may prove useful in predicting the evolutionary trajectory- for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score, assigned to individual haplotypes in a sample. The HAF score naturally captures many of the properties shared by haplotypes carrying an adaptive allele. We provide a theoretical model for the behavior of the HAF score under different evolutionary scenarios, and validate the interpretation of the statistic with simulated data. We develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the adaptive allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft selective sweeps, as well as on data from well-known sweeps in human populations.
机译:大量研究了检测自然选择的基因组特征的方法,并且已经成功地识别了许多选择性扫描。对于这些扫描的绝大多数,自适应等位基因仍然是未知的,这使得很难将扫描的携带者与非携带者区分开。由于正在进行的选择性扫描的载体可能包含未来的最新共同祖先,因此识别它们可能被证明可用于预测进化轨迹,例如在涉及耐药性病原体菌株或癌症亚克隆的情况下。本文的主要贡献是开发和分析了新的统计数据,即单倍型等位基因频率(HAF)得分,该统计值分配给样本中的单个单倍型。 HAF分数自然捕获了携带适应性等位基因的单倍型共有的许多特性。我们提供了在不同进化情况下HAF得分行为的理论模型,并使用模拟数据验证了统计量的解释。我们开发了一种算法(PreCIOSS:预测正在进行的选择性扫描的载波)来识别选择性扫描中的自适应等位基因的载波,并且我们展示了其对硬和软选择性扫描的仿真以及来自知名扫描的数据的能力在人口中。

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