HLA-VBSeq: accurate HLA typing at full resolution from whole-genome sequencing data.
HLA-VBSeq: accurate HLA typing at full resolution from whole-genome sequencing data.
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DOI：
10.1186/1471-2164-16-s2-s7
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发表时间：
2015
期刊：
影响因子：
4.4
通讯作者：
Nagasaki M
中科院分区：
文献类型：
--
作者：
Nariai N;Kojima K;Saito S;Mimori T;Sato Y;Kawai Y;Yamaguchi-Kabata Y;Yasuda J;Nagasaki M
人类白细胞抗原（HLA）基因在决定器官移植的结果中起着重要作用，并且与许多人类疾病有关。由于HLA基因座的多样性和多态性，即使使用全基因组测序数据，高分辨率的HLA分型也具有挑战性。我们已经开发了一种计算工具，HLA-VBSeq，估计最可能的HLA等位基因在全（8位）分辨率从全基因组序列数据。HLA-VBSeq通过变分贝叶斯推断同时优化HLA等位基因序列的读段比对和HLA等位基因上读段的丰度。通过对不同覆盖深度的模拟数据和人类三人样本的真实的测序数据进行HLA I类（HLA-A、-B和-C）和II类（HLA-DQA 1、-DQB 1和-DRB 1）基因座的预测分析，我们证明了所提出的方法相对于其他方法的有效性。HLA-VBSeq是一种高效、准确的HLA分型方法，它使用高通量测序数据，而不需要针对HLA基因座设计引物。此外，它不假设关于HLA等位基因频率的任何先验知识，因此HLA-VBSeq广泛适用于从遗传多样性群体获得的人类样品。
Human leucocyte antigen (HLA) genes play an important role in determining the outcome of organ transplantation and are linked to many human diseases. Because of the diversity and polymorphisms of HLA loci, HLA typing at high resolution is challenging even with whole-genome sequencing data. We have developed a computational tool, HLA-VBSeq, to estimate the most probable HLA alleles at full (8-digit) resolution from whole-genome sequence data. HLA-VBSeq simultaneously optimizes read alignments to HLA allele sequences and abundance of reads on HLA alleles by variational Bayesian inference. We show the effectiveness of the proposed method over other methods through the analysis of predicting HLA types for HLA class I (HLA-A, -B and -C) and class II (HLA-DQA1,-DQB1 and -DRB1) loci from the simulation data of various depth of coverage, and real sequencing data of human trio samples. HLA-VBSeq is an efficient and accurate HLA typing method using high-throughput sequencing data without the need of primer design for HLA loci. Moreover, it does not assume any prior knowledge about HLA allele frequencies, and hence HLA-VBSeq is broadly applicable to human samples obtained from a genetically diverse population.