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DR2S: an integrated algorithm providing reference-grade haplotype sequences from heterozygous samples.

Steffen Klasberg1, Alexander H Schmidt2,3, Vinzenz Lange2

  • 1DKMS Life Science Lab, Dresden, Germany. klasberg@dkms-lab.de.

BMC Bioinformatics
|May 11, 2021
PubMed
Summary
This summary is machine-generated.

DR2S is a new R package that combines sequencing technologies to create high-quality, full-length human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) haplotype sequences for transplantation.

Keywords:
HLAKIRPhasingReference sequencingSequence analysisThird-generation sequencing

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Area of Science:

  • Immunogenetics
  • Bioinformatics
  • Genomic sequencing

Background:

  • High-resolution human leukocyte antigen (HLA) genotyping is critical for hematopoietic stem cell transplantation.
  • Accurate immunogenetic reference sequence databases are essential for HLA typing.

Purpose of the Study:

  • To develop an R package for reconstructing fully-phased, high-quality, full-length haplotype sequences.
  • To improve the accuracy and completeness of reference sequence databases for highly polymorphic genes.

Main Methods:

  • DR2S R package leverages next-generation sequencing (NGS) and third-generation sequencing (TGS) technologies.
  • Combines accuracy of NGS with long-read capabilities of TGS (e.g., PacBio SMRT, ONT nanopore).
  • Applicable to all loci with known reference sequences and available full-length data.

Main Results:

  • DR2S reconstructs fully-phased, high-quality, full-length haplotype sequences.
  • Includes integrated tools for visualization and quality control of reconstructed haplotypes.
  • Optimized for HLA and KIR genes but applicable to other polymorphic regions.

Conclusions:

  • DR2S provides an automated workflow for generating high-quality reference allele sequences.
  • Successfully used to characterize and submit over 500 HLA and 500 KIR alleles to public databases.
  • Enhances the suitability of sequences for submission to public allele databases like IPD-IMGT/HLA and IPD-KIR.