A family-based phasing algorithm for sequence data
A family-based phasing algorithm for sequence data
复制标题
基于家族的序列数据定相算法
DOI：
10.1101/504480
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Battagin M
中科院分区：
文献类型：
--
作者：
Battagin M
本文描述了一种基于家族的定相算法，对于可变覆盖序列数据，该算法首先最小化定相误差，然后最大化定相的等位基因比例。该算法是支持以低成本生成整个种群的高精度序列数据的总体策略的重要工具之一。该算法被称为AlphaFamSeq。它使用关于焦点个体和至少两代祖先的序列数据来确定等位基因的阶段。在第一步中，AlphaFamSeq使用迭代剥离来计算等位基因概率。在随后的步骤中，使用从父母、祖父母和后代的序列数据以及如果有的话，从谱系中的其他家庭获得信息的启发式方法来对等位基因进行分阶段。AlphaFamSeq在一系列模拟数据集上进行了测试。AlphaFamSeq具有较低的相位错误率，如果有足够的序列信息和个体之间的单倍型共享，它可以提供高产量的正确相位等位基因。等位基因阈值对性能的影响较大，窗口大小对性能的影响较小。当对单个家系中的所有个体进行不同覆盖度的测序时，最高的正确等位基因在最大聚集覆盖率的1/6处达到了可能最大值的90%(98.9%)。添加来自其他相关个体的序列信息增加了正确相等位基因的百分比。在所有等位基因频率上的归属表现都很高(标记的平均相关性为0.94%)，除了在很低的频率下略有下降(≤0.01MAF)。在以低成本生成关于整个群体的高精度序列数据的总体策略中，AlphaFamSeq的作用是提供关于焦点个体的非常准确的阶段性单倍型，焦点个体是单倍型在群体中非常常见的个体。
This paper describes a family-based phasing algorithm, for variable-coverage sequence data, that first minimises phasing errors and then maximises the proportion of alleles phased. This algorithm is one of the essential tools that underpin an overall strategy for generating highly accurate sequence data on whole populations at low cost.The algorithm is called AlphaFamSeq. It uses sequence data on the focal individual and at least two generations of ancestors to phase alleles. In the first step, AlphaFamSeq calculates allele probabilities using iterative peeling. In subsequent steps, the alleles are phased using heuristics deriving information from the sequence data of parents, grandparents and progenies and, if available, from other families in the pedigree. AlphaFamSeq was tested on a range of simulated data sets.AlphaFamSeq gives low phasing error rates and, if there is sufficient sequence information and haplotype sharing amongst individuals, it can give a high yield of correctly phased alleles.The allele threshold had a large effect and window size had a small effect on performance. When all individuals in a single family were sequenced at different coverages the highest correctly phased alleles reached 90% of the possible maximum (98.9%) at ~1/6 of the maximum aggregate coverage. Adding sequence information from other related individuals increased the percentage of correctly phased alleles. Imputation performance was high across all allele frequencies (average correlation by marker of 0.94), except for a slight decrease at very low frequencies (≤0.01 MAF).Within an overall strategy for generating highly accurate sequence data on whole populations at low cost the role of AlphaFamSeq is to provide very accurately phased haplotypes on focal individuals, who are individuals whose haplotypes are very common in the population.
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