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Open Access Highly Accessed Methodology article

A fault-tolerant method for HLA typing with PacBio data

Chia-Jung Chang1, Pei-Lung Chen2345, Wei-Shiung Yang234 and Kun-Mao Chao16*

Author Affiliations

1 Department of Computer Science and Information Engineering, National Taiwan University, No.1, Sec.4, Roosevelt Road, Taipei 10617, Taiwan

2 Departments of Medical Genetics and Internal Medicine, National Taiwan University Hospital, No. 8, Chung Shan S. Road, Taipei 10041, Taiwan

3 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, No. 1, Sec. 1, Jen Ai Road, Taipei 10051, Taiwan

4 Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, No.1, Sec.4, Roosevelt Road, Taipei 10617, Taiwan

5 Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, No.1, Sec.4, Roosevelt Road, Taipei 10617, Taiwan

6 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No.1, Sec.4, Roosevelt Road, Taipei 10617, Taiwan

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BMC Bioinformatics 2014, 15:296  doi:10.1186/1471-2105-15-296

Published: 3 September 2014

Abstract

Background

Human leukocyte antigen (HLA) genes are critical genes involved in important biomedical aspects, including organ transplantation, autoimmune diseases and infectious diseases. The gene family contains the most polymorphic genes in humans and the difference between two alleles is only a single base pair substitution in many cases. The next generation sequencing (NGS) technologies could be used for high throughput HLA typing but in silico methods are still needed to correctly assign the alleles of a sample. Computer scientists have developed such methods for various NGS platforms, such as Illumina, Roche 454 and Ion Torrent, based on the characteristics of the reads they generate. However, the method for PacBio reads was less addressed, probably owing to its high error rates. The PacBio system has the longest read length among available NGS platforms, and therefore is the only platform capable of having exon 2 and exon 3 of HLA genes on the same read to unequivocally solve the ambiguity problem caused by the “phasing” issue.

Results

We proposed a new method BayesTyping1 to assign HLA alleles for PacBio circular consensus sequencing reads using Bayes’ theorem. The method was applied to simulated data of the three loci HLA-A, HLA-B and HLA-DRB1. The experimental results showed its capability to tolerate the disturbance of sequencing errors and external noise reads.

Conclusions

The BayesTyping1 method could overcome the problems of HLA typing using PacBio reads, which mostly arise from sequencing errors of PacBio reads and the divergence of HLA genes, to some extent.

Keywords:
HLA typing; NGS; PacBio