Hybrid peeling for fast and accurate calling, phasing, and imputation with sequence data of any coverage in pedigrees
Hybrid peeling for fast and accurate calling, phasing, and imputation with sequence data of any coverage in pedigrees
复制标题
DOI：
10.1186/s12711-018-0438-2
复制
发表时间：
2018-12-18
影响因子：
4.1
通讯作者：
Hickey, John M.
中科院分区：
文献类型：
--
作者：
Whalen, Andrew;Ros-Freixedes, Roger;Hickey, John M.
背景在本文中，我们扩展了多点迭代剥离方法，以提供一种计算上有效的方法来调用、定相和输入任何覆盖范围内的小或大家系的序列数据。我们的方法，称为杂交剥离，使用多位点迭代剥离来估计在一个座位子集上父母和他们的后代之间共享的染色体片段，然后使用单基因位点迭代剥离来聚集多个世代的基因组信息。结果使用一个合成数据集，我们首先分析了杂交剥离在只包含一个焦点个体及其父母和祖父母的不相连家庭中的调用和分期的性能。其次，在一个完整的一般家系的背景下，我们分析了杂交剥离对呼唤和分期基因型的表现。第三，我们分析了混合剥离将全基因组序列数据输入到种群中未测序的个体的性能。我们发现，通过利用相关个体的序列信息，杂交剥离大大增加了被呼叫和分阶段的基因类型的数量。与仅使用父母和祖父母的简化家系相比，使用完整家系时的呼叫率和准确率都有所提高。最后，混合剥离算法将全基因组序列准确地归于未测序的个体。结论我们相信，该算法将能够在许多家系群体中生成低成本和高精度的全基因组序列数据。我们将该算法作为一个名为AlphaPeel的独立程序提供。
BackgroundIn this paper, we extend multi-locus iterative peeling to provide a computationally efficient method for calling, phasing, and imputing sequence data of any coverage in small or large pedigrees. Our method, called hybrid peeling, uses multi-locus iterative peeling to estimate shared chromosome segments between parents and their offspring at a subset of loci, and then uses single-locus iterative peeling to aggregate genomic information across multiple generations at the remaining loci.ResultsUsing a synthetic dataset, we first analysed the performance of hybrid peeling for calling and phasing genotypes in disconnected families, which contained only a focal individual and its parents and grandparents. Second, we analysed the performance of hybrid peeling for calling and phasing genotypes in the context of a full general pedigree. Third, we analysed the performance of hybrid peeling for imputing whole-genome sequence data to non-sequenced individuals in the population. We found that hybrid peeling substantially increased the number of called and phased genotypes by leveraging sequence information on related individuals. The calling rate and accuracy increased when the full pedigree was used compared to a reduced pedigree of just parents and grandparents. Finally, hybrid peeling imputed accurately whole-genome sequence to non-sequenced individuals.ConclusionsWe believe that this algorithm will enable the generation of low cost and high accuracy whole-genome sequence data in many pedigreed populations. We make this algorithm available as a standalone program called AlphaPeel.