Comparison of the accuracy of methods of computational haplotype inference using a large empirical dataset.
Comparison of the accuracy of methods of computational haplotype inference using a large empirical dataset.
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DOI：
10.1186/1471-2156-5-22
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发表时间：
2004-08-03
期刊：
影响因子：
2.9
通讯作者：
Adkins RM
中科院分区：
文献类型：
--
作者：
Adkins RM
单倍型水平的遗传数据分析提供了更高的准确性和推断基因型-表型相关性和基因座进化历史的能力。然而，单倍型的经验测定是昂贵和费力的。因此，已经提出了几种从非定相基因型数据推断单倍型的方法，但尚不清楚每种方法的准确性如何或哪种方法更上级。使用基于15个SNP的308个经验确定的单倍型的大集合比较计算单倍型推断的一些领先方法（PL-EM、Phase、SNPHAP、Haplotyper）的准确性，其中观察到发生36个单倍型。这项研究提出了几个优点，许多以前的比较单倍型推断方法：大量的主题包括，已知的单倍型的数量远小于调查的染色体数量，连锁不平衡值的范围，存在罕见的SNP等位基因，以及相当大的分散在单倍型的频率。与以前的一些单倍型推断方法的比较相反，在将单倍型分配给个体或估计单倍型频率方面，各种方法的准确性差异很小。虽然没有一种方法推断出所有已知的单倍型，但对受试者的单倍型分配对于多达三个SNP的杂合个体是约90%正确的，并且对于多达五个杂合位点是约80%正确的。所有的方法都确定了频率高于1%的每一个单倍型，没有一个将频率高于1%的单倍型分配给不正确的单倍型。所有的单倍型推断方法都具有很高的准确性，并且人们可以对任何一种方法所做出的推断具有信心。鉴定甚至罕见（≥ 1%）的单倍型的能力对于鉴定在相当大比例的人群中导致疾病的单倍型的努力是令人放心的。单倍型的分配是相对准确的受试者杂合多达5个位点，这可能是最大数量的SNP，其中一个应该定义单倍型块或有信心在单倍型分配。
Analyses of genetic data at the level of haplotypes provide increased accuracy and power to infer genotype-phenotype correlations and evolutionary history of a locus. However, empirical determination of haplotypes is expensive and laborious. Therefore, several methods of inferring haplotypes from unphased genotypic data have been proposed, but it is unclear how accurate each of the methods is or which methods are superior. The accuracy of some of the leading methods of computational haplotype inference (PL-EM, Phase, SNPHAP, Haplotyper) are compared using a large set of 308 empirically determined haplotypes based on 15 SNPs, among which 36 haplotypes were observed to occur. This study presents several advantages over many previous comparisons of haplotype inference methods: a large number of subjects are included, the number of known haplotypes is much smaller than the number of chromosomes surveyed, a range in values of linkage disequilibrium, presence of rare SNP alleles, and considerable dispersion in the frequencies of haplotypes. In contrast to some previous comparisons of haplotype inference methods, there was very little difference in the accuracy of the various methods in terms of either assignment of haplotypes to individuals or estimation of haplotype frequencies. Although none of the methods inferred all of the known haplotypes, the assignment of haplotypes to subjects was about 90% correct for individuals heterozygous for up to three SNPs and was about 80% correct for up to five heterozygous sites. All of the methods identified every haplotype with a frequency above 1%, and none assigned a frequency above 1% to an incorrect haplotype. All of the methods of haplotype inference have high accuracy and one can have confidence in inferences made by any one of the methods. The ability to identify even rare (≥ 1%) haplotypes is reassuring for efforts to identify haplotypes that contribute to disease in a significant proportion of a population. Assignment of haplotypes is relatively accurate among subjects heterozygous for up to 5 sites, and this might be the largest number of SNPs for which one should define haplotype blocks or have confidence in haplotype assignments.
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