Fast and accurate HLA typing from short-read next-generation sequence data with xHLA - PubMed (original) (raw)

. 2017 Jul 25;114(30):8059-8064.

doi: 10.1073/pnas.1707945114. Epub 2017 Jul 3.

Zhen Xuan Yeo 2, Marie Wong 2, Jason Piper 2, Tao Long 3, Ewen F Kirkness 3, William H Biggs 3, Ken Bloom 3, Stephen Spellman 4, Cynthia Vierra-Green 4, Colleen Brady 4, Richard H Scheuermann 5 6, Amalio Telenti 3, Sally Howard 3, Suzanne Brewerton 2, Yaron Turpaz 2 3, J Craig Venter 7 5

Affiliations

Chao Xie et al. Proc Natl Acad Sci U S A. 2017.

Abstract

The HLA gene complex on human chromosome 6 is one of the most polymorphic regions in the human genome and contributes in large part to the diversity of the immune system. Accurate typing of HLA genes with short-read sequencing data has historically been difficult due to the sequence similarity between the polymorphic alleles. Here, we introduce an algorithm, xHLA, that iteratively refines the mapping results at the amino acid level to achieve 99-100% four-digit typing accuracy for both class I and II HLA genes, taking only [Formula: see text]3 min to process a 30× whole-genome BAM file on a desktop computer.

Keywords: MHC; autoimmune diseases; transplantation.

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Conflict of interest statement

Conflict of interest statement: C.X., Z.X.Y., M.W., J.P., T.L., E.F.K., W.H.B., K.B., A.T., S.H., S.B., Y.T., and J.C.V. are employees of Human Longevity Inc. There is a patent pending on the technique presented in this work.

Figures

Fig. 1.

Fig. 1.

Overview of the xHLA algorithm.

Fig. 2.

Fig. 2.

Iterative allele set update considering all pairwise-shared exons.

Fig. 3.

Fig. 3.

Second-round iterative allele set refinement.

Fig. 4.

Fig. 4.

Full-resolution HLA typing as a downstream step after four-digit typing.

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