A comparison of phasing algorithms for trios and unrelated individuals
A comparison of phasing algorithms for trios and unrelated individuals
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DOI：
10.1086/500808
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发表时间：
2006-03-01
影响因子：
9.8
通讯作者：
Donnelly, P
中科院分区：
文献类型：
--
作者：
Marchini, J;Cutler, D;Donnelly, P
单倍型相位的知识对于疾病、群体和进化遗传学研究中的许多分析方法是有价值的。大量的研究工作致力于发展从基因型数据推断单倍型相位的统计和计算方法。虽然已经开发了大量这样的方法，但它们主要集中在无关个体的推断上，并且方法之间的比较相当有限。在这里，我们描述了五个领先的算法处理父亲，母亲，孩子三人组的相位推断的扩展。我们进行了全面评估的方法适用于三人组和无关的个人，重点是基因组规模的问题，使用模拟数据和数据的HapMap项目。最准确的算法是PHASE（v2.1）。对于这种方法，其相位被错误推断的基因型的百分比分别为0.12%，0.05%和0.16%的模拟数据，人类多态性研究中心（CEPH）三重奏，和HapMap Yoruban三重奏，分别为5.2%和5.9%的模拟数据和HapMap CEPH数据中的无关个体。在这项工作中考虑的其他方法有可比的，但略差的错误率。Trios的错误率与预期的基因分型错误和缺失数据水平相似。因此，我们得出结论，所有的方法考虑将提供高度准确的估计单倍型时，适用于三人数据集。不同方法的运行时间有很大差异。尽管PHASE（v2.1）是最慢的方法之一，但它用于推断100万SNP HapMap数据集的单倍型。最后，我们评估了估计一对SNP之间的r（2）值的方法，并得出结论，当估计值接近0.8时，所有方法都能很好地估计r（2）。
Knowledge of haplotype phase is valuable for many analysis methods in the study of disease, population, and evolutionary genetics. Considerable research effort has been devoted to the development of statistical and computational methods that infer haplotype phase from genotype data. Although a substantial number of such methods have been developed, they have focused principally on inference from unrelated individuals, and comparisons between methods have been rather limited. Here, we describe the extension of five leading algorithms for phase inference for handling father-mother-child trios. We performed a comprehensive assessment of the methods applied to both trios and to unrelated individuals, with a focus on genomic-scale problems, using both simulated data and data from the HapMap project. The most accurate algorithm was PHASE (v2.1). For this method, the percentages of genotypes whose phase was incorrectly inferred were 0.12%, 0.05%, and 0.16% for trios from simulated data, HapMap Centre d'Etude du Polymorphisme Humain (CEPH) trios, and HapMap Yoruban trios, respectively, and 5.2% and 5.9% for unrelated individuals in simulated data and the HapMap CEPH data, respectively. The other methods considered in this work had comparable but slightly worse error rates. The error rates for trios are similar to the levels of genotyping error and missing data expected. We thus conclude that all the methods considered will provide highly accurate estimates of haplotypes when applied to trio data sets. Running times differ substantially between methods. Although it is one of the slowest methods, PHASE (v2.1) was used to infer haplotypes for the 1 million-SNP HapMap data set. Finally, we evaluated methods of estimating the value of r(2) between a pair of SNPs and concluded that all methods estimated r(2) well when the estimated value was similar to 0.8.