Carvajal-Rodríguez Antonio
Centro de Investigación Mariña (CIM), Departamento de Bioquímica, Genética e Inmunología, Universidade de Vigo, Vigo, 36310 Spain.
Biol Methods Protoc. 2024 Nov 27;9(1):bpae089. doi: 10.1093/biomethods/bpae089. eCollection 2024.
A large number of methods have been developed and continue to evolve for detecting the signatures of selective sweeps in genomes. Significant advances have been made, including the combination of different statistical strategies and the incorporation of artificial intelligence (machine learning) methods. Despite these advances, several common problems persist, such as the unknown null distribution of the statistics used, necessitating simulations and resampling to assign significance to the statistics. Additionally, it is not always clear how deviations from the specific assumptions of each method might affect the results. In this work, allelic classes of haplotypes are used along with the informational interpretation of the Price equation to design a statistic with a known distribution that can detect genomic patterns caused by selective sweeps. The statistic consists of Jeffreys divergence, also known as the population stability index, applied to the distribution of allelic classes of haplotypes in two samples. Results with simulated data show optimal performance of the statistic in detecting divergent selection. Analysis of real severe acute respiratory syndrome coronavirus 2 genome data also shows that some of the sites playing key roles in the virus's fitness and immune escape capability are detected by the method. The new statistic, called , is incorporated into the iHDSel (informed HacDivSel) software available at https://acraaj.webs.uvigo.es/iHDSel.html.
已经开发出大量方法并不断发展,用于检测基因组中选择性清除的特征。已经取得了重大进展,包括不同统计策略的结合以及人工智能(机器学习)方法的纳入。尽管有这些进展,但仍存在几个常见问题,例如所用统计量的未知零分布,这就需要进行模拟和重采样来赋予统计量显著性。此外,并不总是清楚偏离每种方法的特定假设会如何影响结果。在这项工作中,单倍型的等位基因类别与普赖斯方程的信息解释一起被用于设计一种具有已知分布的统计量,该统计量可以检测由选择性清除引起的基因组模式。该统计量由杰弗里斯散度(也称为群体稳定性指数)组成,应用于两个样本中单倍型等位基因类别的分布。模拟数据的结果表明该统计量在检测分歧选择方面具有最佳性能。对真实的严重急性呼吸综合征冠状病毒2基因组数据的分析也表明,该方法检测到了一些在病毒适应性和免疫逃逸能力中起关键作用的位点。这个名为 的新统计量已被纳入可在https://acraaj.webs.uvigo.es/iHDSel.html获取的iHDSel(知情HacDivSel)软件中。