ATHLATES: accurate typing of human leukocyte antigen through exome sequencing - PubMed (original) (raw)

ATHLATES: accurate typing of human leukocyte antigen through exome sequencing

Chang Liu et al. Nucleic Acids Res. 2013 Aug.

Abstract

Human leukocyte antigen (HLA) typing at the allelic level can in theory be achieved using whole exome sequencing (exome-seq) data with no added cost but has been hindered by its computational challenge. We developed ATHLATES, a program that applies assembly, allele identification and allelic pair inference to short read sequences, and applied it to data from Illumina platforms. In 15 data sets with adequate coverage for HLA-A, -B, -C, -DRB1 and -DQB1 genes, ATHLATES correctly reported 74 out of 75 allelic pairs with an overall concordance rate of 99% compared with conventional typing. This novel approach should be broadly applicable to research and clinical laboratories.

PubMed Disclaimer

Figures

Figure 1.

Figure 1.

Workflow of allelic HLA typing using exome-seq data. Exome-seq data are first filtered by comparison against all alleles of HLA genes obtained from IMGT/HLA database, and then fed into ATHLATES for in silico allelic HLA typing without human supervision.

Figure 2.

Figure 2.

Coverage of target genes by exome-seq data and comparison of HLA typing results among conventional typing, ATHLATES and HLAminer. (A) Fold coverage at exons of each of the five target HLA genes. Paired-end reads are aligned to the typed alleles of individual samples, and the fold coverage data from all 15 samples are presented. Median coverage (gray lines) and range (gray areas) are plotted over alignment positions for individual HLA genes. Dotted lines are exon boundaries, and the exons are numbered below each plot. The disruptions in curves are caused by mapping the reads to an alignment coordinate based on a MSA of all alleles of a target gene. The insertions present in rare alleles make the curves appear to be discontinuous. The one or two exons toward the 3′ end are exceedingly short (e.g. 5 bp for exon 8 of HLA-A) and hence, may not be reliably aligned against. (B) Concordance rates of HLA typing results by ATHLATES and HLAminer as compared with conventional Sanger-based method for the 15 data sets with adequate coverage.

Similar articles

Cited by

References

    1. Lind C, Ferriola D, Mackiewicz K, Heron S, Rogers M, Slavich L, Walker R, Hsiao T, McLaughlin L, D'Arcy M, et al. Next-generation sequencing: the solution for high-resolution, unambiguous human leukocyte antigen typing. Hum. Immunol. 2010;71:1033–1042. - PubMed
    1. Erlich H. HLA DNA typing: past, present, and future. Tissue Antigens. 2012;80:1–11. - PubMed
    1. Gabriel C, Danzer M, Hackl C, Kopal G, Hufnagl P, Hofer K, Polin H, Stabentheiner S, and Proll J. Rapid high-throughput human leukocyte antigen typing by massively parallel pyrosequencing for high-resolution allele identification. Hum. Immunol. 2009;70:960–964. - PubMed
    1. Bentley G, Higuchi R, Hoglund B, Goodridge D, Sayer D, Trachtenberg EA, Erlich HA. High-resolution, high-throughput HLA genotyping by next-generation sequencing. Tissue Antigens. 2009;74:393–403. - PMC - PubMed
    1. Erlich RL, Jia X, Anderson S, Banks E, Gao X, Carrington M, Gupta N, DePristo MA, Henn MR, Lennon NJ, et al. Next-generation sequencing for HLA typing of class I loci. BMC Genomics. 2011;12:42. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources