scholarly journals Computational Approaches to Facilitate Epitope-Based HLA Matching in Solid Organ Transplantation

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Kirsten Geneugelijk ◽  
Jeroen Wissing ◽  
Dirk Koppenaal ◽  
Matthias Niemann ◽  
Eric Spierings

Epitope-based HLA matching has been emerged over the last few years as an improved method for HLA matching in solid organ transplantation. The epitope-based matching concept has been incorporated in both the PIRCHE-II and the HLAMatchmaker algorithm to find the most suitable donor for a recipient. For these algorithms, high-resolution HLA genotype data of both donor and recipient is required. Since high-resolution HLA genotype data is often not available, we developed a computational method which allows epitope-based HLA matching from serological split level HLA typing relying on HLA haplotype frequencies. To validate this method, we simulated a donor-recipient population for which PIRCHE-II and eplet values were calculated when using both high-resolution HLA genotype data and serological split level HLA typing. The majority of the serological split level HLA-determined ln(PIRCHE-II)/ln(eplet) values did not or only slightly deviate from the reference group of high-resolution HLA-determined ln(PIRCHE-II)/ln(eplet) values. This deviation was slightly increased when HLA-C or HLA-DQ was omitted from the input and was substantially decreased when using two-field resolution HLA genotype data of the recipient and serological split level HLA typing of the donor. Thus, our data suggest that our computational approach is a powerful tool to estimate PIRCHE-II/eplet values when high-resolution HLA genotype data is not available.

2019 ◽  
Vol 19 (7) ◽  
pp. 1955-1963 ◽  
Author(s):  
Yanping Huang ◽  
Anh Dinh ◽  
Steven Heron ◽  
Allison Gasiewski ◽  
Carolina Kneib ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (23) ◽  
pp. e180-e183 ◽  
Author(s):  
Eduardo Nunes ◽  
Helen Heslop ◽  
Marcelo Fernandez-Vina ◽  
Cynthia Taves ◽  
Dawn R. Wagenknecht ◽  
...  

Abstract Histocompatibility testing for stem cell and solid organ transplantation has become increasingly complex as newly discovered HLA alleles are described. HLA typing assignments reported by laboratories are used by physicians and donor registries for matching donors and recipients. To communicate effectively, a common language for histocompatibility terms should be established. In early 2010, representatives from Clinical, Registry, and Histocompatibility organizations joined together as the Harmonization of Histocompatibility Typing Terms Working Group to define a consensual language for laboratories, physicians, and registries to communicate histocompatibility typing information. The Working Group defined terms for HLA typing resolution, HLA matching, and a format for reporting HLA assignments. In addition, definitions of verification typing and extended typing were addressed. The original draft of the Definitions of Histocompatibility Typing Terms was disseminated to colleagues from each organization to gain feedback and create a collaborative document. Commentary gathered during this 90-day review period were discussed and implemented for preparation of this report. Histocompatibility testing continues to evolve; thus, the definitions agreed on today probably will require refinement and perhaps additional terminology in the future.


2009 ◽  
Vol 70 ◽  
pp. S36
Author(s):  
Cindy H. Park ◽  
Angelo N. Arnold ◽  
Darshana Dadhania ◽  
Vijay K. Sharma ◽  
Rex Friedlander ◽  
...  

2019 ◽  
Vol 36 (7) ◽  
pp. 2157-2164 ◽  
Author(s):  
Estelle Geffard ◽  
Sophie Limou ◽  
Alexandre Walencik ◽  
Michelle Daya ◽  
Harold Watson ◽  
...  

Abstract Motivation The HLA system plays a pivotal role in both clinical applications and immunology research. Typing HLA genes in patient and donor is indeed required in hematopoietic stem cell and solid-organ transplantation, and the histocompatibility complex region exhibits countless genetic associations with immune-related pathologies. Since the discovery of HLA antigens, the HLA system nomenclature and typing methods have constantly evolved, which leads to difficulties in using data generated with older methodologies. Results Here, we present Easy-HLA, a web-based software suite designed to facilitate analysis and gain knowledge from HLA typing, regardless of nomenclature or typing method. Easy-HLA implements a computational and statistical method of HLA haplotypes inference based on published reference populations containing over 600 000 haplotypes to upgrade missing or partial HLA information: ‘HLA-Upgrade’ tool infers high-resolution HLA typing and ‘HLA-2-Haplo’ imputes haplotype pairs and provides additional functional annotations (e.g. amino acids and KIR ligands). We validated both tools using two independent cohorts (total n = 2500). For HLA-Upgrade, we reached a prediction accuracy of 92% from low- to high-resolution of European genotypes. We observed a 96% call rate and 76% accuracy with HLA-2-Haplo European haplotype pairs prediction. In conclusion, Easy-HLA tools facilitate large-scale immunogenetic analysis and promotes the multi-faceted HLA expertise beyond allelic associations by providing new functional immunogenomics parameters. Availability and implementation Easy-HLA is a web application freely available (free account) at: https://hla.univ-nantes.fr. Supplementary information Supplementary data are available at Bioinformatics online.


2021 ◽  
Vol 40 (2) ◽  
pp. 21-32
Author(s):  
Svetlana N. Kolyubaeva ◽  
Liliya A. Myakoshina ◽  
Marina I. Eliseeva ◽  
Ruslan I. Glushakov

The antigen system on the surface of human cells is responsible for recognizing foreign antigens. In organ transplantation, the immune system reacts to all foreign antigens that are different from the recipients antigens. In practice, solid organ transplantation is carried out with varying degrees of genetic discrepancy, while the main principle that should be followed to prevent acute and chronic transplant rejection reactions is to avoid unacceptable discrepancies. As a result, the diagnosis of typing genes of histocompatibility allows you to select a donor to which the recipient will not have sensitization. The article presents an analysis of various methods for typing human histocompatibility genes for organ and tissue transplantation. The discovery of the polymerase chain reaction was a new stage in the typing of human histocompatibility genes, which made it possible to develop new methods of gene typing. As a result, methods have been developed for typing genes using sequencers, including a new-generation MiSeq sequencer (Illumina, USА), a Massarray genomic time-of-flight analyzer (Agena Bioscience, USA). The use of sequencing has led to the possibility of simultaneous typing from 24 to 100 DNA samples. Modern technological solutions have made it possible to improve the 3rd generation NGS sequencers and provide a maximum productivity of up to 30 billion nucleotides per run, minimize restrictions on the length of DNA readings, as well as track parameters, control the sequencing process and conduct base-scaling in real time. Modern data using rapid genes typing of the human histocompatibility system (MinION Oxford nanopore) meet the needs of particularly sensitive recipients. Preliminary evidence suggests that this method will be more economical and efficient and will replace all previous ones over time (8 figs, bibliography: 40 refs).


2017 ◽  
Vol 78 ◽  
pp. 140
Author(s):  
Kirsten Geneugelijk ◽  
Jeroen Wissing ◽  
Matthias Niemann ◽  
Dirk Koppenaal ◽  
Eric Spierings

2017 ◽  
Vol 141 (3) ◽  
pp. 329-340 ◽  
Author(s):  
Ross M. Fasano ◽  
Harold Cliff Sullivan ◽  
Robert A. Bray ◽  
Howard M. Gebel ◽  
Erin K. Meyer ◽  
...  

Current genotyping methodologies for transplantation and transfusion management employ multiplex systems that allow for simultaneous detection of multiple HLA antigens, human platelet antigens, and red blood cell (RBC) antigens. The development of high-resolution, molecular HLA typing has led to improved outcomes in unrelated hematopoietic stem cell transplants by better identifying compatible alleles of the HLA-A, B, C, DRB1, and DQB1 antigens. In solid organ transplantation, the combination of high-resolution HLA typing with solid-phase antibody identification has proven of value for highly sensitized patients and has significantly reduced incompatible crossmatches at the time of organ allocation. This database-driven, combined HLA antigen/antibody testing has enabled routine implementation of “virtual crossmatching” and may even obviate the need for physical crossmatching. In addition, DNA-based testing for RBC antigens provides an alternative typing method that mitigates many of the limitations of hemagglutination-based phenotyping. Although RBC genotyping has utility in various transfusion settings, it has arguably been most useful for minimizing alloimmunization in the management of transfusion-dependent patients with sickle cell disease or thalassemia. The availability of high-throughput RBC genotyping for both individuals and large populations of donors, along with coordinated informatics systems to compare patients' antigen profiles with available antigen-negative and/or rare blood-typed donors, holds promise for improving the efficiency, reliability, and extent of RBC matching for this population.


2017 ◽  
Vol 36 (5) ◽  
pp. 445-448 ◽  
Author(s):  
Jennifer L. Lee ◽  
Cyd K. Eaton ◽  
Kristin Loiselle Rich ◽  
Bonney Reed-Knight ◽  
Rochelle S. Liverman ◽  
...  

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