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首页> 外文期刊>BMC Genomics >ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis
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ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis

机译：ARG-walker：通过种群基因组学分析推断减数分裂重组热点的个体比强度

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Background Meiotic recombination hotspots play important roles in various aspects of genomics, but the underlying mechanisms for regulating the locations and strengths of recombination hotspots are not yet fully revealed. Most existing algorithms for estimating recombination rates from sequence polymorphism data can only output average recombination rates of a population, although there is evidence for the heterogeneity in recombination rates among individuals. For genome-wide association studies (GWAS) of recombination hotspots, an efficient algorithm that estimates the individualized strengths of recombination hotspots is highly desirable. Results In this work, we propose a novel graph mining algorithm named ARG-walker, based on random walks on ancestral recombination graphs (ARG), to estimate individual-specific recombination hotspot strengths. Extensive simulations demonstrate that ARG-walker is able to distinguish the hot allele of a recombination hotspot from the cold allele. Integrated with output of ARG-walker, we performed GWAS on the phased haplotype data of the 22 autosome chromosomes of the HapMap Asian population samples of Chinese and Japanese (JPT+CHB). Significant cis- regulatory signals have been detected, which is corroborated by the enrichment of the well-known 13-mer motif CCNCCNTNNCCNC of PRDM9 protein. Moreover, two new DNA motifs have been identified in the flanking regions of the significantly associated SNPs (single nucleotide polymorphisms), which are likely to be new cis- regulatory elements of meiotic recombination hotspots of the human genome. Conclusions Our results on both simulated and real data suggest that ARG-walker is a promising new method for estimating the individual recombination variations. In the future, it could be used to uncover the mechanisms of recombination regulation and human diseases related with recombination hotspots.
机译：背景减数分裂重组热点在基因组学的各个方面都起着重要的作用，但是调控重组热点的位置和强度的潜在机制尚未完全揭示。从序列多态性数据估计重组率的大多数现有算法只能输出总体的平均重组率，尽管有证据表明个体之间重组率的异质性。对于重组热点的全基因组关联研究（GWAS），非常需要一种有效的算法来估计重组热点的个性化强度。结果在这项工作中，我们提出了一种新的图挖掘算法ARG-walker，它基于祖先重组图（ARG）上的随机游走来估计特定于个体的重组热点强度。大量的模拟表明，ARG-walker能够将重组热点的热等位基因与冷等位基因区分开。结合ARG-walker的输出，我们对HapMap亚洲人和日本人（JPT + CHB）样本的22个常染色体的分阶段单倍型数据进行了GWAS。已检测到重要的顺式调控信号，这通过PRDM9蛋白众所周知的13-mer基序CCNCCNTNNCCNC的富集得到证实。此外，在显着相关的SNPs（单核苷酸多态性）的侧翼区域中已经发现了两个新的DNA模体，这很可能是人类基因组减数重组热点的新的顺式调控元件。结论我们在模拟和真实数据上的结果都表明ARG-walker是一种有前途的估计单个重组变异的新方法。将来，它可用于揭示重组调控机制以及与重组热点相关的人类疾病。

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