Resolving MiSeq-Generated Ambiguities in HLA-DPB1 Typing by Using the Oxford Nanopore Technology

Jamie L. Duke, Timothy L. Mosbruger, Deborah Ferriola, Nilesh Chitnis, Taishan Hu, Nikolaos Tairis, David J. Margolis, Dimitri S. Monos

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The technical limitations of current next-generation sequencing technologies, combined with an ever-increasing number of human leukocyte antigen (HLA) alleles, form the basis for the additional ambiguities encountered at an increasing rate in clinical practice. HLA-DPB1 characterization, particularly, generates a significant percentage of ambiguities (25.5%), posing a challenge for accurate and unambiguous HLA-DPB1 genotyping. Phasing of exonic heterozygous positions between exon 2 and all other downstream exons has been the major cause of ambiguities. In this study, the Oxford Nanopore MinION, a third-generation sequencing technology, was used to resolve the phasing. The accurate MiSeq sequencing data, combined with the long reads obtained from the MinION platform, allow for the resolution of the tested ambiguities.

Original languageEnglish (US)
Pages (from-to)852-861
Number of pages10
JournalJournal of Molecular Diagnostics
Volume21
Issue number5
DOIs
StatePublished - Sep 2019
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

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