New challenges, new opportunities: Next generation sequencing and its place in the advancement of HLA typing

Bravo-Egaña, Valia; Sanders, Holly; Chitnis, Nilesh

doi:10.1016/j.humimm.2021.01.010

Cited by 29 publications

(24 citation statements)

References 86 publications

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“…Over the past decade, NGS has rapidly replaced the more conventional HLA typing methods providing more accurate high-resolution typing ( 60 , 61 ). In addition, RNA-based NGS technologies have enabled simultaneous expression analysis and identification of expression quantitative trait loci (eQTLs) ( 11 ).…”

Section: Methods In Hla Expression Quantificationmentioning

confidence: 99%

HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation

2022

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Varying HLA allele-specific expression levels are associated with human diseases, such as graft versus host disease (GvHD) in hematopoietic stem cell transplantation (HSCT), cytotoxic T cell response and viral load in HIV infection, and the risk of Crohn’s disease. Only recently, RNA-based next generation sequencing (NGS) methodologies with accompanying bioinformatics tools have emerged to quantify HLA allele-specific expression replacing the quantitative PCR (qPCR) -based methods. These novel NGS approaches enable the systematic analysis of the HLA allele-specific expression changes between individuals and between normal and disease phenotypes. Additionally, analyzing HLA allele-specific expression and allele-specific expression loss provide important information for predicting efficacies of novel immune cell therapies. Here, we review available RNA sequencing-based approaches and computational tools for NGS to quantify HLA allele-specific expression. Moreover, we explore recent studies reporting disease associations with differential HLA expression. Finally, we discuss the role of allele-specific expression in HSCT and how considering the expression quantification in recipient-donor matching could improve the outcome of HSCT.

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Section: Methods In Hla Expression Quantificationmentioning

confidence: 99%

HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation

2022

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“…In the early days, the MHC class I genes were mostly typed by defining only exons 2 and 3, which encode for the antigen binding site, whereas MHC class II entities were distinguished by exon 2 alone. [34][35][36] The typing of KIR genes focused mainly on determining the presence or absence of specific gene segments, with only a few approaches that defined their polymorphic exons at allele level resolution. [37][38][39][40][41] These elementary typing strategies were, however, often unable to phase heterozygous ambiguities and to distinguish alleles that display variation outside of the targeted exons.…”

Section: Full-length Gene Characterization By Sequence Specific Ampli...mentioning

confidence: 99%

HLA/MHC and KIR characterization in humans and non‐human primates using Oxford Nanopore Technologies and Pacific Biosciences sequencing platforms

Bruijnesteijn

2023

HLA

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The gene products of the HLA/MHC and KIR multigene families are important modulators of the immune system and are associated with health and disease. Characterization of the genes encoding these receptors has been integrated into different biomedical applications, including transplantation and reproduction biology, immune therapies and in fundamental research into disease susceptibility or resistance. Conventional short‐read sequencing strategies have shown their value in high throughput typing, but are insufficient to uncover the entire complexity of the highly polymorphic HLA/MHC and KIR gene systems. The implementation of single‐molecule and real‐time sequencing platforms, offered by Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT), revolutionized the fields of genomics and transcriptomics. Using fundamentally distinct principles, these platforms generate long‐read data that can unwire the plasticity of the HLA/MHC and KIR genes, including high‐resolution characterization of genes, alleles, phased haplotypes, transcription levels and epigenetics modification patterns. These insights might have profound clinical relevance, such as improved matching of donors and patients in clinical transplantation, but could also lift disease association studies to a higher level. Even more, a comprehensive characterization may refine animal models in preclinical studies. In this review, the different HLA/MHC and KIR characterization approaches using PacBio and ONT platforms are described and discussed.

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“…Depending on their power to discriminate between HLA alleles, DNA-based HLA typing methods are characterized by low resolution (result at the level of the digits composing the first field in the HLA nomenclature) and high resolution (result at the level of four digits) [ 110 ]. The most widely used DNA-based methods in conjunction with PCR for HLA typing include sequence-specific oligonucleotides (SSO), sequence-specific primers (SSP), and sequence-based typing (SBT) [ 111 ]. In PCR-SSO, PCR products are hybridized into sequence-specific oligonucleotide probes.…”

Section: Challenges In Hla Typing To Predict Disease Outcomesmentioning

confidence: 99%

“…NGS-based HLA typing has been implemented with better accuracy compared to traditional HLA typing methods [ 120 ]. NGS-based HLA typing approaches are promising but are not yet ready to be implemented in routine clinical care settings due to the higher cost and complex protocol [ 111 ].…”

Section: Challenges In Hla Typing To Predict Disease Outcomesmentioning

confidence: 99%

Human Leukocyte Antigen (HLA) System: Genetics and Association with Bacterial and Viral Infections

Medhasi

Chantratita

2022

Journal of Immunology Research

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The human leukocyte antigen (HLA) system is one of the most crucial host factors influencing disease progression in bacterial and viral infections. This review provides the basic concepts of the structure and function of HLA molecules in humans. Here, we highlight the main findings on the associations between HLA class I and class II alleles and susceptibility to important infectious diseases such as tuberculosis, leprosy, melioidosis, Staphylococcus aureus infection, human immunodeficiency virus infection, coronavirus disease 2019, hepatitis B, and hepatitis C in populations worldwide. Finally, we discuss challenges in HLA typing to predict disease outcomes in clinical implementation. Evaluation of the impact of HLA variants on the outcome of bacterial and viral infections would improve the understanding of pathogenesis and identify those at risk from infectious diseases in distinct populations and may improve the individual treatment.

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New challenges, new opportunities: Next generation sequencing and its place in the advancement of HLA typing

Cited by 29 publications

References 86 publications

HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation

HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation

HLA/MHC and KIR characterization in humans and non‐human primates using Oxford Nanopore Technologies and Pacific Biosciences sequencing platforms

Human Leukocyte Antigen (HLA) System: Genetics and Association with Bacterial and Viral Infections

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