Long Read Sequencing for Transplantation

Transplantation is the best therapeutic option for a wide range of end-stage diseases, improving quality and longevity of life. Human leukocyte antigen (HLA) typing is fundamental to the success of organ or bone marrow transplantation, enabling HLA matching of donor and recipient. Long-read sequencing has become a valuable tool in the field of transplantation, especially in understanding the complex interactions between the donor and recipient immune systems. CD Genomics is a leading global life sciences company providing specialized long read sequencing solutions for transplantation research. We aim to improve the chances of successful transplantation by identifying rare and complex HLA alleles.

Introduction to HLA

The human leukocyte antigen ( HLA ) system, also known as the major histocompatibility complex (MHC), spans more than 4 Mb on chromosome 6 and plays a central role in normal immune function, autoimmune disease, and transplantation. Any cells displaying other HLA types are "non-self" and are viewed as invaders by the body's immune system, leading to the rejection of tissues containing these cells. This is especially important for transplanted tissue, as it can lead to transplantation rejection. Due to the importance of HLA in transplantation, the HLA locus is the most commonly typed locus by serology and PCR. Matching HLA gene polymorphisms by high-resolution DNA sequence analysis is the gold standard for determining compatibility between HSCT patients and donors.

In recent years, next-generation sequencing (NGS), which is primarily based on short-read-long sequencing technologies, has replaced traditional HLA typing methods, providing higher throughput and resolution and shorter turnaround times. However, such methods succumb to the inherent limitations of short read, which are often poorly aligned to HLA alleles and make the phasing of distant variants challenging. Nanopore sequencing is considered a rapid and cost-effective option for HLA typing. Although raw read accuracy is low, typing accuracy has been reported to be encouraging, and long reads from this platform provide the added benefit of improved distant variant phasing.

Fig. 1. Gaps in HLA typing technologies. (Liu et al., 2021)

Solutions Offering at CD Genomics

Our advanced sequencing platforms, such as PacBio SMRT sequencing and ONT Nanopore sequencing platforms, have enabled researchers to perform highly accurate and comprehensive HLA typing. CD Genomics is committed to providing long read sequencing solutions to identify rare and complex HLA alleles to meet the specific needs of transplantation research. Our solutions provide high-resolution, stage-specific HLA typing data to ensure epitope matching between donors and recipients of solid organ transplants.

Our long read sequencing solutions for transplantation include, but are not limited to:

• Identification of Rare and Complex HLA Alleles

The HLA region is highly polymorphic with a large number of single nucleotide polymorphisms (SNPs) and insertional deletions. Traditional short-read sequencing methods often struggle to accurately compare and identify variants within the HLA gene. Our long read sequencing platform provides you with a comprehensive view of the HLA allele by explicitly phasing SNVs to the corresponding haplotype across a large portion of the HLA region. Our long read sequencing solutions can also identify novel HLA alleles.

• High-Resolution HLA Typing

High-resolution HLA typing is critical for successful transplantation. Our long read sequencing provides accurate, detailed HLA typing results. Long reads help detect combinations of variants within a single phase sequence, allowing for accurate genotyping of HLA class I and class II loci.

• Long Read Transcriptome Analysis of GVHD

Plant-versus-host disease (GVHD) is a serious complication that can occur after transplantation, in which the donor's immune cells attack the recipient's tissues. We offer long read sequencing that enables transcriptome analysis of immune cells involved in GVHD, helping you to identify gene expression patterns associated with the onset and severity of GVHD, and providing valuable information to understand the underlying molecular mechanisms.

• KIR Gene Analysis

The killer cell immunoglobulin-like receptor (KIR) genes encode receptors expressed on natural killer (NK) cells that play a critical role in immune surveillance and regulation. We offer long read sequencing solutions to analyze KIR gene diversity and the association between specific KIR genotypes and the occurrence of transplantation rejection.

Advantages of Our Long Read Sequencing Solutions for Transplantation

• Long read sequencing overcomes the problems associated with short-read sequencing and improves the accuracy of HLA typing.
• The ability of long read sequencing to span the entire HLA region alters variant detection by easily linking neighboring variants together, allowing SNVs to be phased to their respective haplotypes.
• The efficient method of phased determination of HLA alleles helps to identify other important markers, thereby improving transplantation success.
• Long read sequencing can call variants within regulatory regions and these variants have the potential to affect gene expression.
• With fast sample-to-answer times, rapid and accurate HLA typing can significantly impact patient outcomes.

CD Genomics is committed to providing accurate, comprehensive, and high-resolution long read sequencing solutions to accelerate transplantation research. Our reliable solutions ensure improved HLA typing accuracy in transplantation. If you have any questions, please feel free to contact us. We look forward to working with you on projects of interest.

Related Services

PacBio SMRT Sequencing
Oxford Nanopore Sequencing
Human Leukocyte Antigen (HLA) Typing