DR2S

DR2S reconstructs fully-phased, high-quality full-length haplotype sequences for HLA and KIR genes by integrating short-read NGS accuracy with long-read PacBio SMRT and Oxford Nanopore Technologies nanopore sequencing to support high-resolution genotyping in contexts such as hematopoietic stem cell transplantation.

Key Features:

• Algorithm and R package: Implemented as a bioinformatics algorithm and R package for high-resolution genotyping workflows.
• Integration of sequencing technologies: Combines short-read next-generation sequencing (NGS) accuracy with long-read PacBio SMRT and Oxford Nanopore Technologies nanopore sequencing read lengths for hybrid reconstruction.
• Full-length phased haplotype reconstruction: Produces fully-phased, high-quality full-length haplotype and reference allele sequences for highly polymorphic loci.
• Applicability across loci: Optimized for HLA and KIR genes and applicable to any loci with known reference sequences given availability of full-length sequencing data.
• Automated workflow: Automates generation of fully-phased reference allele sequences for highly polymorphic gene regions.
• Visualization and quality control tools: Includes integrated tools for visualization and quality control of reconstructed haplotypes to support submission to allele databases.

Scientific Applications:

• Hematopoietic stem cell transplantation genotyping: Enables precise HLA typing for donor-recipient matching in hematopoietic stem cell transplantation.
• Immunogenetics reference expansion: Has been used to characterize and submit over 500 HLA alleles and more than 500 KIR alleles to the IPD-IMGT/HLA and IPD-KIR databases.
• General high-resolution genotyping: Applicable to high-resolution genotyping of highly polymorphic loci when full-length sequencing data and reference sequences are available.

Methodology:

DR2S leverages dual sequencing technologies by integrating short-read NGS with long-read PacBio SMRT and Oxford Nanopore Technologies nanopore data to combine accuracy and read length for reconstructing fully-phased, full-length haplotype sequences.