Hla-mapper: An application to optimize the mapping of HLA sequences produced by massively parallel sequencing procedures
Hla-mapper: An application to optimize the mapping of HLA sequences produced by massively parallel sequencing procedures
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DOI：
10.1016/j.humimm.2018.06.010
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发表时间：
2018-09-01
期刊：
影响因子：
2.7
通讯作者：
Mendes-Junior, Celso Teixeira
中科院分区：
文献类型：
--
作者：
Castelli, Erick C.;Paz, Michelle A.;Mendes-Junior, Celso Teixeira
当通过第二代测序一起评估多于一个HLA基因时，具有挑战性的任务是实现可靠的读段作图。HLA基因的多态性和重复性可能会使读段作图过程产生偏差，通常会低估非常多态性片段的变异性，或高估某些片段的变异性。为了克服这个问题，我们开发了hla-mapper，它考虑了来自IPD-IMGT/HLA数据库的HLA序列和未发表的HLA序列，以应用评分系统。这就简化了每个读段对的评估，将它们寻址到它们最可能来源的HLA基因。Ma-mapper提供了一个可靠的HLA序列图，允许精确的下游分析，如变异识别，单倍型推断和等位基因分型。此外，hla-mapper支持全基因组、外显子组和靶向测序数据。为了评估与传统映射算法相比的软件性能，我们使用了三种不同的模拟数据集来比较使用hla映射器，BWA MEM和Bowtie 2获得的结果。总的来说，主要对于经典的HLA I类基因，hla-作图仪表现出上级性能，最大限度地减少了当使用BWA MEM或Bowtie 2与单个参考基因组时通常观察到的错误作图和交叉作图。
A challenging task when more than one HLA gene is evaluated together by second-generation sequencing is to achieve a reliable read mapping. The polymorphic and repetitive nature of HLA genes might bias the read mapping process, usually underestimating variability at very polymorphic segments, or overestimating variability at some segments. To overcome this issue we developed hla-mapper, which takes into account HLA sequences derived from the IPD-IMGT/HLA database and unpublished HLA sequences to apply a scoring system. This comprehends the evaluation of each read pair, addressing them to the most likely HLA gene they were derived from. Ma-mapper provides a reliable map of HLA sequences, allowing accurate downstream analysis such as variant calling, haplotype inference, and allele typing. Moreover, hla-mapper supports whole genome, exome, and targeted sequencing data. To assess the software performance in comparison with traditional mapping algorithms, we used three different simulated datasets to compare the results obtained with hla-mapper, BWA MEM, and Bowtie2. Overall, hla-mapper presented a superior performance, mainly for the classical HLA class I genes, minimizing wrong mapping and cross-mapping that are typically observed when using BWA MEM or Bowtie2 with a single reference genome.