Accurate HLA Typing at High-Digit Resolution from NGS Data

Authors: Yazhi Huang, Jing Yang, Dingge Ying, Yan Zhang, Vorasuk Shotelersuk, Nattiya Hirankarn, Pak Chung Sham, Yu Lung Lau, Wanling Yang

Abstract:

Human leukocyte antigen (HLA) typing from next generation sequencing (NGS) data has the potential for applications in clinical laboratories and population genetic studies. Here we introduce a novel technique for HLA typing from NGS data based on read-mapping using a comprehensive reference panel containing all known HLA alleles and de novo assembly of the gene-specific short reads. An accurate HLA typing at high-digit resolution was achieved when it was tested on publicly available NGS data, outperforming other newly-developed tools such as HLAminer and PHLAT.

Keywords: Human leukocyte antigens, next generation sequencing, whole exome sequencing, HLA typing.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1338172

References:

[1] de Bakker PI, McVean G, Sabeti PC, et al., “A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC,” Nat Genet, vol. 38, 2006, pp. 1166–1172.
[2] de Bakker PI, Raychaudhuri S., “Interrogating the major histocompatibility complex with high-throughput genomics,” Hum Mol Genet, vol. 21, 2012, pp. 29–36.
[3] IMGT/HLA (International immunogenetics project/Human major histocompatibility complex). London: Royal Free Hospital, Anthony Nolan Research Institute, HLA Informatics Group, 1998. http://www.ebi.ac.uk/ipd/imgt/hla/.
[4] Bentley G, Higuchi R, Hoglund B, et al. High-resolution, high-throughput HLA genotyping by next-generation sequencing. Tissue Antigens, vol. 74, 2009, pp. 393–403.
[5] Lind C, Ferriola D, Mackiewicz K, et al., “Next-generation sequencing: the solution for high-resolution, unambiguous human leukocyte antigen typing,” Hum Immunol, vol. 10, 2010, pp. 1033–1042.
[6] Noble JA, Martin A, Valdes AM, et al., “Type 1 diabetes risk for HLA-DR3 haplotypes depends on genotypic context: Association of DPB1 and HLA class I loci among DR3 and DR4 matched Italian patients and controls,” Hum Immunol, vol. 69, 2008, pp. 291–300.
[7] Solberg OD, Mack SJ, Lancastera AK, et al, “Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies,” Hum Immunol, vol. 69, 2008, pp. 443–464.
[8] Boegel S, Lower M, Schafer M, et al, “HLA typing from RNA-Seq sequence reads,” Genome Med, vol. 4, 2012, pp. 102–113.
[9] Warren RL, Choe G, Freeman D, et al, “Derivation of HLA types from shotgun sequence datasets,” Genome Med, vol. 4, 2012, pp. 95–102.
[10] Gonzalez-Galarza FF, Christmas S, Middleton D, et al., “Allele frequency net: a database and online repository for immune gene frequencies in worldwide populations,” Nucleic Acids Res, vol. 39, 2011, pp. 913-919.
[11] Li H, Durbin R, “Fast and accurate long-read alignment with Burrows-Wheeler Transform,” Bioinformatics, vol. 26, 2010, pp. 589–595.
[12] Inflammgen (The laboratory in genetics and genomic medicine of inflammation). http://www.inflammgen.org/.
[13] Erlich RL, Jia X, Anderson S, et al., “Next-generation sequencing for HLA typing of class I loci,” BMC Genomics, vol. 12, 2011, pp. 42-54.
[14] Bai Y, Ni M, Cooper B, et al., “Inference of high resolution HLA types using genome-wide RNA or DNA sequencing reads,” BMC Genomics, vol. 15, 2014, pp. 325-340.
[15] Stephens M, Smith NJ, Donnelly P, “A new statistical method for haplotype reconstruction from population data,” Am J Hum Genet, vol. 68, 2001, pp. 978–989.
[16] Major E, Rigo K, Hague T, et al., “HLA typing from 1000 genomes whole genome and whole exome illumina data,” PLoS ONE, vol. 8, 2013, pp. 11–19.
[17] RefSeq (NCBI reference sequence database). Bethesda: National Library of Medicine, National Center for Biotechnology Information, 2002. http://www.ncbi.nlm.nih.gov/refseq/.