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Next-generation sequencing HLA

Denis C Bauer, Armella Zadoorian, Laurence O W Wilson, Natalie P Thorne
MOTIVATION: Despite being essential for numerous clinical and research applications, high-resolution human leukocyte antigen (HLA) typing remains challenging and laboratory tests are also time-consuming and labour intensive. With next-generation sequencing data becoming widely accessible, on-demand in silico HLA typing offers an economical and efficient alternative. RESULTS: In this study we evaluate the HLA typing accuracy and efficiency of five computational HLA typing methods by comparing their predictions against a curated set of > 1000 published polymerase chain reaction-derived HLA genotypes on three different data sets (whole genome sequencing, whole exome sequencing and transcriptomic sequencing data)...
November 1, 2016: Briefings in Bioinformatics
Yuxin Yin, James H Lan, David Nguyen, Nicole Valenzuela, Ping Takemura, Yung-Tsi Bolon, Brianna Springer, Katsuyuki Saito, Ying Zheng, Tim Hague, Agnes Pasztor, Gyorgy Horvath, Krisztina Rigo, Elaine F Reed, Qiuheng Zhang
BACKGROUND: Unambiguous HLA typing is important in hematopoietic stem cell transplantation (HSCT), HLA disease association studies, and solid organ transplantation. However, current molecular typing methods only interrogate the antigen recognition site (ARS) of HLA genes, resulting in many cis-trans ambiguities that require additional typing methods to resolve. Here we report high-resolution HLA typing of 10,063 National Marrow Donor Program (NMDP) registry donors using long-range PCR by next generation sequencing (NGS) approach on buccal swab DNA...
2016: PloS One
Hisham A Edinur, Siti M Manaf, Nor F Che Mat
The successful of transplantation is determined by the shared human leukocyte antigens (HLAs) and ABO blood group antigens between donor and recipient. In recent years, killer cell receptor [i.e., killer cell immunoglobulin-like receptor (KIR)] and major histocompatibility complex (MHC) class I chain-related gene molecule (i.e., MICA) were also reported as important determinants of transplant compatibility. At present, several different genotyping techniques (e.g., sequence specific primer and sequence based typing) can be used to characterize blood group, HLA, MICA and KIR and loci...
September 24, 2016: World Journal of Transplantation
Peter M Clark, Jamie L Duke, Deborah Ferriola, Valia Bravo-Egana, Tunde Vago, Aniqa Hassan, Anna Papazoglou, Dimitri Monos
BACKGROUND: Routine, high-resolution human leukocyte antigen (HLA) genotyping by next generation sequencing within clinical immunogenetics laboratories can now provide the full-length gene sequence characterization of fully phased HLA alleles. This powerful technique provides insights into HLA variation beyond the traditionally characterized antigen recognition domain, providing sequence annotation across the entire gene including untranslated and intronic regions and may be used to characterize novel alleles from massively parallel sequencing runs...
December 2016: Clinical Chemistry
Antonietta Picascia, Vincenzo Grimaldi, Claudio Napoli
The complex polymorphism of the HLA genes and the need of a proper identification of anti-HLA antibodies have led to continuously develop novel practical and feasible technologies in the field of organ and tissue transplantation. Technologies to identify HLA molecules have evolved from the serological to the molecular methods and a true innovation in the DNA sequencing has taken place with the development of next generation sequencing. An interesting field to explore is how the information resulting from the HLA-DNA sequencing can be applied in the clinical setting by including the alloimmunization assessment...
October 2016: Transplantation Reviews
T Profaizer, E Lázár-Molnár, D W Close, J C Delgado, A Kumánovics
Implementation of human leukocyte antigen (HLA) genotyping by next-generation sequencing (NGS) in the clinical lab brings new challenges to the laboratories performing this testing. With the advent of commercially available HLA-NGS typing kits, labs must make numerous decisions concerning capital equipment and address labor considerations. Therefore, careful and unbiased evaluation of available methods is imperative. In this report, we compared our in-house developed HLA NGS typing with two commercially available kits from Illumina and Omixon using 10 International Histocompatibility Working Group (IHWG) and 36 clinical samples...
July 2016: HLA
Virginie Moalic-Allain, Bernard Mercier, Paul Gueguen, Claude Ferec
Current high resolution HLA typing technologies produce ambiguous results, and it is often necessary to perform additionnal tests to resolve these ambiguities. Next generation sequencing is a promising technology, which can overcome this problem. It is going to usher a new strategy to determine HLA compatibility between donor and recipient. It can lead to non ambiguous results by analysing the full amplified sequence of HLA genes and by eliminating heterozygote phase ambiguities. Instead, as many new techniques, we can face several problems, such as analysis difficulties because of incomplete HLA sequences in the database or errors related to the sequencing instrumentation...
August 1, 2016: Annales de Biologie Clinique
Markus W Löffler, P Anoop Chandran, Karoline Laske, Christopher Schroeder, Irina Bonzheim, Mathias Walzer, Franz J Hilke, Nico Trautwein, Daniel J Kowalewski, Heiko Schuster, Marc Günder, Viviana A Carcamo Yañez, Christopher Mohr, Marc Sturm, Huu-Phuc Nguyen, Olaf Riess, Peter Bauer, Sven Nahnsen, Silvio Nadalin, Derek Zieker, Jörg Glatzle, Karolin Thiel, Nicole Schneiderhan-Marra, Stephan Clasen, Hans Bösmüller, Falko Fend, Oliver Kohlbacher, Cécile Gouttefangeas, Stefan Stevanović, Alfred Königsrainer, Hans-Georg Rammensee
BACKGROUND & AIMS: We report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5year course of the disease, the initial tumor mass, two local recurrences and a lung metastasis were surgically removed. Lacking alternative treatment options, aiming at the induction of anti-tumor T cells responses, we initiated a personalized multi-peptide vaccination, based on in-depth analysis of tumor antigens (immunopeptidome) and sequencing...
October 2016: Journal of Hepatology
Eric T Weimer, Maureen Montgomery, Rosanne Petraroia, John Crawford, John L Schmitz
High-resolution human leukocyte antigen (HLA) matching reduces graft-versus-host disease and improves overall patient survival after hematopoietic stem cell transplant. Sanger sequencing has been the gold standard for HLA typing since 1996. However, given the increasing number of new HLA alleles identified and the complexity of the HLA genes, clinical HLA typing by Sanger sequencing requires several rounds of additional testing to provide allele-level resolution. Although next-generation sequencing (NGS) is routinely used in molecular genetics, few clinical HLA laboratories use the technology...
September 2016: Journal of Molecular Diagnostics: JMD
M Teresa Ciudad, Nicoletta Sorvillo, Floris P van Alphen, Diego Catalán, Alexander B Meijer, Jan Voorberg, Dolores Jaraquemada
Dendritic cells (DCs) are the major professional APCs of the immune system; however, their MHC-II-associated peptide repertoires have been hard to analyze, mostly because of their scarce presence in blood and tissues. In vitro matured human monocyte-derived DCs (MoDCs) are widely used as professional APCs in experimental systems. In this work, we have applied mass spectrometry to identify the HLA-DR-associated self-peptide repertoires from small numbers of mature MoDCs (∼5 × 10(6) cells), derived from 7 different donors...
June 30, 2016: Journal of Leukocyte Biology
C Lucan, Laura-Ancuta Pop, A Florian, Valentina Pileczki, B Petrushev, Delia Dima, Ioana Frinc, Ioana Berindan-Neagoe, A Irimie, C Berce, I-S Florian, Anca Bojan, C Tomuleasa
From an oncological perspective, the second most common malignancies in children are brain tumors. Despite the recent therapeutic breakthroughs in this field, concerning surgery, radiotherapy and chemotherapy alike, some cases still have poor outcomes in curability. This is especially the case in patients with high-risk histological types of tumors, and those suffering from residual, remitting and disseminated diseases. Due to the unique neuroanatomical emplacement of brain tumors and their aggressive infiltrative behavior, their total removal remains a demanding task...
April 2016: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
Laurent Abi-Rached, Didier Raoult
With the advent of next-generation sequencing, paleogenetics has considerably expanded over the past few years and notably encompassed the characterization of the genomes of archaic humans who lived more than 30,000 years ago. These paleogenetics investigations have revealed that admixture between modern and archaic humans occurred, with Neanderthals having contributed to 1.5% to 2.1% of modern Eurasian genomes, and Denisovans to 3% to 6% of modern Melanesian genomes and to approximately 0.2% of modern Asian genomes...
June 2016: Microbiology Spectrum
(no author information available yet)
No abstract text is available yet for this article.
June 2016: Annals of Intensive Care
Nilakshi Samaranayake, Sumadhya D Fernando, Nilaksha F Neththikumara, Chaturaka Rodrigo, Nadira D Karunaweera, Vajira H W Dissanayake
BACKGROUND: The outcome of leishmaniasis is an interplay between Leishamania and the host. Identifying contributory host genetic factors is complicated by the variability in phenotype, ethnicity and parasite species. Leishmaniasis is caused exclusively by L. donovani in Sri Lanka with localized cutaneous leishmaniasis (LCL) being the predominant form. We report here an association study of human leucocyte antigen (HLA) class I and II genes with LCL in Sri Lanka, the first on HLA associations in cutaneous leishmaniasis in a South Asian population...
2016: BMC Infectious Diseases
G Zeng, Y Huang, Y Huang, Z Lyu, D Lesniak, P Randhawa
This study interrogates the antigen-specificity of inflammatory infiltrates in renal biopsies with BK polyomavirus (BKPyV) viremia (BKPyVM) with or without allograft nephropathy (BKPyVN). Peripheral blood mononuclear cells (PBMC) from five healthy HLA-A0101 subjects were stimulated by peptides derived from the BKPYV proteome or polymorphic regions of HLA. Next generation sequencing of the T cell-receptor complementary DNA was performed on peptide-stimulated PBMC and 23 biopsies with T cell-mediated rejection (TCMR) or BKPyVN...
November 2016: American Journal of Transplantation
Vanja Paunić, Loren Gragert, Joel Schneider, Carlheinz Müller, Martin Maiers
Unrelated stem cell registries have been collecting HLA typing of volunteer bone marrow donors for over 25years. Donor selection for hematopoietic stem cell transplantation is based primarily on matching the alleles of donors and patients at five polymorphic HLA loci. As HLA typing technologies have continually advanced since the beginnings of stem cell transplantation, registries have accrued typings of varied HLA typing ambiguity. We present a new typing resolution score (TRS), based on the likelihood of self-match, that allows the systematic comparison of HLA typings across different methods, data sets and populations...
July 2016: Human Immunology
J Emmery, R Hachmon, C W Pyo, W C Nelson, D E Geraghty, A M N Andersen, M Melbye, T V F Hviid
A line of investigations indicate that genes in the human leukocyte antigen (HLA) complex are involved in a successful acceptance of the semiallogeneic fetus during pregnancy. In this study, associations between specific HLA class Ia (HLA-A and -B) and class II (HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) alleles and the risk of developing severe preeclampsia/eclampsia were investigated in a detailed and large-scale study. In total, 259 women diagnosed with severe preeclampsia or eclampsia and 260 matched control women with no preeclampsia, together with their neonates, were included in the study...
June 2016: Genes and Immunity
Mariet Allen, Michaela Kachadoorian, Minerva M Carrasquillo, Aditya Karhade, Lester Manly, Jeremy D Burgess, Chen Wang, Daniel Serie, Xue Wang, Joanna Siuda, Fanggeng Zou, High Seng Chai, Curtis Younkin, Julia Crook, Christopher Medway, Thuy Nguyen, Li Ma, Kimberly Malphrus, Sarah Lincoln, Ronald C Petersen, Neill R Graff-Radford, Yan W Asmann, Dennis W Dickson, Steven G Younkin, Nilüfer Ertekin-Taner
OBJECTIVE: To investigate the top late-onset Alzheimer disease (LOAD) risk loci detected or confirmed by the International Genomics of Alzheimer's Project for association with brain gene expression levels to identify variants that influence Alzheimer disease (AD) risk through gene expression regulation. METHODS: Expression levels from the cerebellum (CER) and temporal cortex (TCX) were obtained using Illumina whole-genome cDNA-mediated annealing, selection, extension, and ligation assay (WG-DASL) for ∼400 autopsied patients (∼200 with AD and ∼200 with non-AD pathologies)...
August 2015: Neurology. Genetics
Raphael Carapito, Mirjana Radosavljevic, Seiamak Bahram
The human Major Histocompatibility Complex, known as the "Human Leukocyte Antigen (HLA)", could be defined as a "super locus" (historically called "supergene") governing the adaptive immune system in vertebrates. It also harbors genes involved in innate immunity. HLA is the most gene-dense, polymorphic and disease-associated region of the human genome. It is of critical medical relevance given its involvement in the fate of the transplanted organs/tissues and its association with more than 100 diseases. However, despite these important roles, comprehensive sequence analysis of the 4 megabase HLA locus has been limited due to technological challenges...
April 5, 2016: Human Immunology
Paraskevi Vogiatzi
BACKGROUND: The shortage of suitable organs and achieved tolerance are uncontested main concerns in transplantation. Long waiting lists for deceased donors and limited numbers of living donors are the current scenarios. Kidney grafts from living donors have better overall survival compared to cadaveric and require less aggressive immunosuppressive regimens. The human leukocyte antigen (HLA) labs have the key role to test the recipient and donors compatibility based on typing and antibody profile...
2016: Transplantation Research
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