HLA Haplotype Validator for quality assessments of HLA typing

Abstract

HLA alleles are observed in specific haplotypes, due to linkage disequilibrium (LD) between particular alleles. Haplotype frequencies for alleles in strong LD have been established for specific ethnic groups and racial categories. Application of high-resolution HLA typing using Next Generation Sequencing (NGS) is becoming a common practice in research and clinical laboratory settings. HLA typing errors using NGS occasionally occur due to allelic sequence imbalance or misalignment. Manual inspection of HLA genotypes is labor intensive and requires an in-depth knowledge of HLA alleles and haplotypes. We developed the “HLA Haplotype Validator (HLAHapV)” software, which inspects an HLA genotype for both the presence of common and well-documented alleles and observed haplotypes. The software also reports warnings when rare alleles, or alleles that do not belong to recognized haplotypes, are found. The software validates observable haplotypes in genotype data providing increased confidence regarding the accuracy of the HLA typing, thus reducing the effort involved in correcting potential HLA typing errors. The HLAHapV software is a powerful tool for quality control of HLA genotypes prior to the application of downstream analyses. We demonstrated the use of the HLAHapV software for identifying unusual haplotypes leading to finding potential HLA typing errors.

Computational Approaches to Facilitate Epitope-Based HLA Matching in Solid Organ Transplantation

“…For example, a similar approach as our approach has been used by Madbouly et al for the imputation of high-resolution HLA genotypes from multilocus unphased genotypes with ambiguous or missing typing data [ 25 ]. In addition, the HLA Haplotype Validator described by Osoegawa et al uses HLA haplotype frequency tables to extract all potential HLA haplotype constellations to identify potential errors in HLA genotyping [ 26 ]. Furthermore, HaploStats from the National Marrow Donor Program (available via http://www.haplostats.org/ ) also estimates the most likely high-resolution HLA genotypes, but without HLA loci linkage removal when no matching high-resolution HLA haplotype is found.…”

A comparative reference study for the validation of HLA‐matching algorithms in the search for allogeneic hematopoietic stem cell donors and cord blood units

“…In contrast to HLA typing methodology, there are no established regulatory frameworks in place for HMAs. However, previous validation efforts for the estimation of HLA haplotype frequencies by the WMDA ITWG Registry Diversity working group are not only a building block for this study but are also used in the validation of HLA typing techniques .…”

The combinatorial diversity of KIR and HLA class I allotypes in Peninsular Malaysia

“…New allele sequences were deposited in GenBank and the ImmunoPolymorphism Database 18 . The HLA alleles were determined using NGSengine 2.10.0 (GenDX, Utrecht, the Netherlands) and HLA*LA, 42 with any discrepancies resolved using HLA Haplotype Validator 43 …”