DR2S: an Integrated Algorithm Providing Reference-grade Haplotype Sequences from Heterozygous Samples

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2021 May 11

PMID 33971817

Citations 5

Authors

Steffen Klasberg

Alexander H Schmidt

Vinzenz Lange

Gerhard Schofl

Affiliations

Soon will be listed here.

Abstract

Background: High resolution HLA genotyping of donors and recipients is a crucially important prerequisite for haematopoetic stem-cell transplantation and relies heavily on the quality and completeness of immunogenetic reference sequence databases of allelic variation.

Results: Here, we report on DR2S, an R package that leverages the strengths of two sequencing technologies-the accuracy of next-generation sequencing with the read length of third-generation sequencing technologies like PacBio's SMRT sequencing or ONT's nanopore sequencing-to reconstruct fully-phased high-quality full-length haplotype sequences. Although optimised for HLA and KIR genes, DR2S is applicable to all loci with known reference sequences provided that full-length sequencing data is available for analysis. In addition, DR2S integrates supporting tools for easy visualisation and quality control of the reconstructed haplotype to ensure suitability for submission to public allele databases.

Conclusions: DR2S is a largely automated workflow designed to create high-quality fully-phased reference allele sequences for highly polymorphic gene regions such as HLA or KIR. It has been used by biologists to successfully characterise and submit more than 500 HLA alleles and more than 500 KIR alleles to the IPD-IMGT/HLA and IPD-KIR databases.

Citing Articles

Submitting Novel Full-Length HLA, MIC, and KIR Alleles with TypeLoader2.

Schone B, Fuhrmann M, Surendranath V, Schmidt A, Lange V, Schofl G Methods Mol Biol. 2024; 2809:157-169.

PMID: 38907897 DOI: 10.1007/978-1-0716-3874-3_11.

High population frequencies of copy number variations originate from independent recombination events.

Klussmeier A, Putke K, Klasberg S, Kohler M, Sauter J, Schefzyk D Front Immunol. 2023; 14:1297589.

PMID: 38035108 PMC: 10684724. DOI: 10.3389/fimmu.2023.1297589.

Comparative genomics of the medicinal plants Lonicera macranthoides and L. japonica provides insight into genus genome evolution and hederagenin-based saponin biosynthesis.

Yin X, Xiang Y, Huang F, Chen Y, Ding H, Du J Plant Biotechnol J. 2023; 21(11):2209-2223.

PMID: 37449344 PMC: 10579715. DOI: 10.1111/pbi.14123.

Nanopore sequencing technology, bioinformatics and applications.

Wang Y, Zhao Y, Bollas A, Wang Y, Au K Nat Biotechnol. 2021; 39(11):1348-1365.

PMID: 34750572 PMC: 8988251. DOI: 10.1038/s41587-021-01108-x.

HLA-E diversity unfolded: Identification and characterization of 170 novel HLA-E alleles.

Paech C, Albrecht V, Putke K, Schofl G, Schone B, Schmidt A HLA. 2021; 97(5):389-398.

PMID: 33527770 PMC: 8247977. DOI: 10.1111/tan.14195.

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