A method for the allocation of sequencing resources in genotyped livestock populations.
A method for the allocation of sequencing resources in genotyped livestock populations.
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DOI：
10.1186/s12711-017-0322-5
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发表时间：
2017-05-18
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影响因子：
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通讯作者：
Hickey JM
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文献类型：
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作者：
Gonen S;Ros-Freixedes R;Battagin M;Gorjanc G;Hickey JM
本文描述了一种称为 AlphaSeqOpt 的方法，用于利用现有的定相基因组数据在牲畜群体中分配测序资源，以最大限度地提高定相能力并将测序单倍型归入整个群体。我们提出两种算法。第一个选择共同代表群体中单倍型多样性的最大可能部分的焦点个体。第二个在焦点个体的家族中分配固定的测序预算，以便能够在序列水平上对其单倍型进行定相。我们在模拟谱系中测试了两种算法的性能。对于每个谱系，我们评估了焦点个体携带的群体单倍型的比例，并将我们的结果与广泛使用的关键祖先方法的变体和两种基于单倍型的方法进行了比较。考虑到分配给其家族的固定测序预算的比例，我们在序列水平上计算了焦点个体单倍型的预期定相准确性。 AlphaSeqOpt 通过三种方式最大限度地提高捕获和定相群体中最常见单倍型的能力。首先，它选择比现有方法共同代表群体单倍型多样性更大部分的焦点个体。其次，它从整个谱系中选择焦点个体，其单倍型可以使用基于家族的定相和插补算法轻松地进行定相，从而最大限度地提高将序列插补到其余群体中的能力。第三，它将更多的固定测序预算分配给单倍型在群体中更频繁的焦点个体，而不是分配给单倍型频率较低的焦点个体。与现有方法不同，我们还提出了一种算法，将部分测序预算分配给焦点个体的家族（即直系祖先），以确保其单倍型可以在序列水平上进行定相，这对于启用和最大化后续序列插补至关重要。我们提出了一种新方法，用于将固定测序预算分配给焦点个人及其家庭，以便最终测序的单倍型在序列水平上进行定相时，代表了可以在该预算下进行测序和定相的群体中单倍型多样性的最大可能部分。本文的在线版本 (doi:10.1186/s12711-017-0322-5) 包含补充材料，可供授权用户使用。
This paper describes a method, called AlphaSeqOpt, for the allocation of sequencing resources in livestock populations with existing phased genomic data to maximise the ability to phase and impute sequenced haplotypes into the whole population. We present two algorithms. The first selects focal individuals that collectively represent the maximum possible portion of the haplotype diversity in the population. The second allocates a fixed sequencing budget among the families of focal individuals to enable phasing of their haplotypes at the sequence level. We tested the performance of the two algorithms in simulated pedigrees. For each pedigree, we evaluated the proportion of population haplotypes that are carried by the focal individuals and compared our results to a variant of the widely-used key ancestors approach and to two haplotype-based approaches. We calculated the expected phasing accuracy of the haplotypes of a focal individual at the sequence level given the proportion of the fixed sequencing budget allocated to its family. AlphaSeqOpt maximises the ability to capture and phase the most frequent haplotypes in a population in three ways. First, it selects focal individuals that collectively represent a larger portion of the population haplotype diversity than existing methods. Second, it selects focal individuals from across the pedigree whose haplotypes can be easily phased using family-based phasing and imputation algorithms, thus maximises the ability to impute sequence into the rest of the population. Third, it allocates more of the fixed sequencing budget to focal individuals whose haplotypes are more frequent in the population than to focal individuals whose haplotypes are less frequent. Unlike existing methods, we additionally present an algorithm to allocate part of the sequencing budget to the families (i.e. immediate ancestors) of focal individuals to ensure that their haplotypes can be phased at the sequence level, which is essential for enabling and maximising subsequent sequence imputation. We present a new method for the allocation of a fixed sequencing budget to focal individuals and their families such that the final sequenced haplotypes, when phased at the sequence level, represent the maximum possible portion of the haplotype diversity in the population that can be sequenced and phased at that budget. The online version of this article (doi:10.1186/s12711-017-0322-5) contains supplementary material, which is available to authorized users.