Comparison of exome-based HLA class I genotyping tools: identification of platform-specific genotyping errors
Comparison of exome-based HLA class I genotyping tools: identification of platform-specific genotyping errors
复制标题
DOI：
10.1038/jhg.2016.141
复制
发表时间：
2017-03-01
影响因子：
3.5
通讯作者：
Nakamura, Yusuke
中科院分区：
文献类型：
--
作者：
Kiyotani, Kazuma;Mai, Tu H.;Nakamura, Yusuke
准确的人类白细胞抗原（HLA）基因分型在涉及免疫系统的研究中至关重要。开发了几种从全外显子组数据估计HLA基因型的算法。我们比较了七种算法的准确性，包括Optitype，Polysolver和PHLAT，以及使用来自1000个基因组计划的12个临床样本和961个个体调查的模式和可能的误判原因。Optitype在第二场分辨率下对HLA I类等位基因的准确性最高，为97.2%，其次是Polysolver的94.0%和PHLAT的85.6%。在Optitype中，161个误判中的34个（21.1%）跨越不同的血清学类型，并且常见的误判是HLA-A * 26：01至HLA-A* 25：01、HLA-B* 45：01至HLA-B* 44：15和HLA-C* 08：02至HLA-C* 05：01，错误率分别为4.1%、10.0%和4.1%。在Polysolver中，345个误判中有193个（55.9%）发生在不同的血清学等位基因上，在93.3%的HLA-A * 25：01携带者中观察到HLA-A * 25：01到HLA-A* 26：01的基因分型错误的特定模式，这是由于在HLA读数的提取过程中HLA-A* 25：01序列读数的丢失。在PHLAT中，246个HLA-A中的147个（59.8%）是由于将多个等位基因错误分配到HLA-A* 01：22或HLA-A* 01：81。这些结果表明，当使用基于外显子组的HLA I类基因分型数据并将这些结果应用于临床时，需要仔细考虑。
Accurate human leukocyte antigen (HLA) genotyping is critical in studies involving the immune system. Several algorithms to estimate HLA genotypes from whole-exome data were developed. We compared the accuracy of seven algorithms, including Optitype, Polysolver and PHLAT, as well as investigated patterns and possible causes of miscalls using 12 clinical samples and 961 individuals from the 1000 Genomes Project. Optitype showed the highest accuracy of 97.2% for HLA class I alleles at the second field resolution, followed by 94.0% in Polysolver and 85.6% in PHLAT. In Optitype, 34 (21.1%) of 161 miscalls were across different serological types, and common miscalls were HLA-A* 26:01 to HLA-A* 25:01, HLA-B* 45:01 to HLA-B* 44:15 and HLA-C* 08:02 to HLA-C* 05:01 with error rates of 4.1%, 10.0% and 4.1%, respectively. In Polysolver, 193 (55.9%) of 345 miscalls occurred across different serological alleles, and a specific pattern of genotyping error from HLA-A* 25:01 to HLA-A* 26:01 was observed in 93.3% of HLA-A* 25:01 carriers, due to dropping of HLA-A* 25:01 sequence reads during the extraction process of HLA reads. In PHLAT, 147 (59.8%) of 246 miscalls in HLA-A were due to erroneous assignment of multiple alleles to either HLA-A* 01:22 or HLA-A* 01:81. These results suggest that careful considerations needed to be taken when using exome-based HLA class I genotyping data and applying these results in clinical settings.