scholarly journals Population Frequencies Determined by Next-generation Sequencing Provide Strategies for Prospective HLA Epitope Matching for Transplantation

2020 ◽  
Author(s):  
Jenny Tran ◽  
Oliver Gunther ◽  
Karen Sherwood ◽  
Franz Fenninger ◽  
Lenka Allan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Renal Transplant ◽  
Human Leukocyte ◽  
Gene Complex ◽  
Next Generation ◽  
Leukocyte Antigen ◽  
Hla Genes ◽  
In Silico Mapping ◽  
High Degree ◽  
Generation Sequencing

Abstract Compatibility for human leukocyte antigen (HLA) genes between transplant donors and recipients improves graft survival but prospective matching is rarely performed due to the vast heterogeneity of this gene complex. To reduce complexity, we have combined next-generation sequencing and in silico mapping to determine population frequencies and matching probabilities of 150 antibody-binding eplets across all 11 classical HLA genes in 2000 ethnically heterogeneous renal patients and donors. We show that eplets are more common and more uniformly distributed between donors and recipients than the respective HLA isoforms. Simulation of targeted eplet matching shows that a high degree of overall compatibility, and perfect identity at the clinically important HLA class II loci, can be obtained within a patient waiting list of approximately 250 subjects. Internal epitope-based allocation is thus feasible for most major renal transplant programs, while regional or national sharing may be required for other solid organs.

scholarly journals High-throughput sequencing defines donor and recipient HLA B-cell epitope frequencies for prospective matching in transplantation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jenny N. Tran ◽  
◽  
Oliver P. Günther ◽  
Karen R. Sherwood ◽  
Franz Fenninger ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Cell Epitope ◽  
Human Leukocyte ◽  
Gene Complex ◽  
Leukocyte Antigen ◽  
Hla Genes ◽  
In Silico Mapping ◽  
B Cell Epitope ◽  
High Degree ◽  
Generation Sequencing

AbstractCompatibility for human leukocyte antigen (HLA) genes between transplant donors and recipients improves graft survival but prospective matching is rarely performed due to the vast heterogeneity of this gene complex. To reduce complexity, we have combined next-generation sequencing and in silico mapping to determine transplant population frequencies and matching probabilities of 150 antibody-binding eplets across all 11 classical HLA genes in 2000 ethnically heterogeneous renal patients and donors. We show that eplets are more common and uniformly distributed between donors and recipients than the respective HLA isoforms. Simulations of targeted eplet matching shows that a high degree of overall compatibility, and perfect identity at the clinically important HLA class II loci, can be obtained within a patient waiting list of approximately 250 subjects. Internal epitope-based allocation is thus feasible for most major renal transplant programs, while regional or national sharing may be required for other solid organs.

scholarly journals A New Human Leukocyte Antigen Typing Algorithm Combined With Currently Available Genotyping Tools Based on Next-Generation Sequencing Data and Guidelines to Select the Most Likely Human Leukocyte Antigen Genotype

2021 ◽  
Vol 12 ◽  
Author(s):  
Miseon Lee ◽  
Jeong-Han Seo ◽  
Sungjae Song ◽  
In Hye Song ◽  
Su Yeon Kim ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Next Generation Sequencing Data ◽  
Next Generation ◽  
Leukocyte Antigen ◽  
Hla Type ◽  
Hla Genotyping ◽  
Ngs Data ◽  
Generation Sequencing

BackgroundHigh-precision human leukocyte antigen (HLA) genotyping is crucial for anti-cancer immunotherapy, but existing tools predicting HLA genotypes using next-generation sequencing (NGS) data are insufficiently accurate.Materials and MethodsWe compared availability, accuracy, correction score, and complementary ratio of eight HLA genotyping tools (OptiType, HLA-HD, PHLAT, seq2HLA, arcasHLA, HLAscan, HLA*LA, and Kourami) using 1,005 cases from the 1000 Genomes Project data. We created a new HLA-genotyping algorithm combining tools based on the precision and the accuracy of tools’ combinations. Then, we assessed the new algorithm’s performance in 39 in-house samples with normal whole-exome sequencing (WES) data and polymerase chain reaction–sequencing-based typing (PCR-SBT) results.ResultsRegardless of the type of tool, the calls presented by more than six tools concordantly showed high accuracy and precision. The accuracy of the group with at least six concordant calls was 100% (97/97) in HLA-A, 98.2% (112/114) in HLA-B, 97.3% (142/146) in HLA-C. The precision of the group with at least six concordant calls was over 98% in HLA-ABC. We additionally calculated the accuracy of the combination tools considering the complementary ratio of each tool and the accuracy of each tool, and the accuracy was over 98% in all groups with six or more concordant calls. We created a new algorithm that matches the above results. It was to select the HLA type if more than six out of eight tools presented a matched type. Otherwise, determine the HLA type experimentally through PCR-SBT. When we applied the new algorithm to 39 in-house cases, there were more than six matching calls in all HLA-A, B, and C, and the accuracy of these concordant calls was 100%.ConclusionsHLA genotyping accuracy using NGS data could be increased by combining the current HLA genotyping tools. This new algorithm could also be useful for preliminary screening to decide whether to perform an additional PCR-based experimental method instead of using tools with NGS data.

scholarly journals Relationship between obstructive sleep apnea and human leukocyte antigen variants

2021 ◽  
Author(s):  
Ayse Gul Zamani ◽  
Sebnem Yosunkaya ◽  
Adil Zamani ◽  
Hulya Vatansev ◽  
Ahmet Burak Arslan ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Next Generation Sequencing ◽  
Sleep Apnea ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Turkish Population ◽  
Next Generation ◽  
Leukocyte Antigen ◽  
Obstructive Sleep ◽  
Generation Sequencing

Background and aim: The obstructive sleep apnea (OSA) is a common, complex and polygenic disease and it has high risk of serious complications. The human leukocyte antigen (HLA) system plays a crucial role in the regulation of immune function by discriminating self from non-self. In recent years there has been rapid advancement in "Next Generation Sequencing" technology. It enables the detection of HLA alleles in four or even six digits, providing a high level of precision. The aim of the present study was to investigate the genetic variants at HLA-A,-B,-C,-DQB1 and -DRB1 loci in OSA patients and unrelated healthy individuals by targeted NGS in the Turkish population. Materials methods: Fifty newly diagnosed patients with OSA and 50 control subjects were enrolled in the study. OSA diagnosis was made by utilizing the apnea-hypopnea index (AHI)≥5 in overnight polysomnography (PSG). Blood samples were obtained in the morning, after PSG. Controls were randomly selected from healthy volunteers who had a low risk for OSA. Genotyping of HLA-A, B, C, DRB1 and DQB1 genes were performed by using next generation sequencing. Results: HLA-A*02:01, HLA-C*03:03:01, HLA-C*14:03, HLA DRB1*04:05 alleles were found more frequently in OSA patients, but not in the controls (p=0.036, p=0.007, p=0.043 and 0.013, respectively). The allele frequencies of HLA-A*03:01 and HLA-B*35:02 were significantly higher in controls compared to OSA patients (p=0.024 and p=0.043). Conclusion: These results suggest that HLA-A*02:01, HLA-C*03:03:01, HLA-C*14:03, HLA DRB1*04:05 alleles may play a predisposing role in the Turkish population with OSA. In addition, HLA-A*03:01 and HLA-B*35:02 alleles may be protective in this population.

Sign in / Sign up

Export Citation Format

Share Document