scholarly journals PharmVIP: A Web-Based Tool for Pharmacogenomic Variant Analysis and Interpretation

2021 ◽  
Vol 11 (11) ◽  
pp. 1230
Author(s):  
Jittima Piriyapongsa ◽  
Chanathip Sukritha ◽  
Pavita Kaewprommal ◽  
Chalermpong Intarat ◽  
Kwankom Triparn ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Web Based ◽  
Leukocyte Antigen ◽  
Genome Wide ◽  
Immune Mediated ◽  
Hla Genotypes ◽  
One Stop ◽  
Potential Risks ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data

The increasing availability of next generation sequencing (NGS) for personal genomics could promote pharmacogenomics (PGx) discovery and application. However, current tools for analysis and interpretation of pharmacogenomic variants from NGS data are inadequate, as none offer comprehensive analytic functions in a simple, web-based platform. In addition, no tools exist to analyze human leukocyte antigen (HLA) genes for determining potential risks of immune-mediated adverse drug reaction (IM-ADR). We describe PharmVIP, a web-based PGx tool, for one-stop comprehensive analysis and interpretation of genome-wide variants obtained from NGS platforms. PharmVIP comprises three main interpretation modules covering analyses of pharmacogenes involved in pharmacokinetics, pharmacodynamics and IM-ADR. The Guideline module provides Clinical Pharmacogenetics Implementation Consortium (CPIC) drug guideline recommendations based on the translation of genotypic data in genes having guidelines. The HLA module reports HLA genotypes, potential adverse drug reactions, and the relevant drug guidelines. The Pharmacogenes module is employed for prioritizing variants according to variant effect on gene function. Detailed, customizable reports are provided as exportable files and as an interactive web version. PharmVIP is a new integrated NGS workflow for the PGx community to facilitate discovery and clinical application.

scholarly journals Accuracy of programs for the determination of HLA alleles from NGS data

2017 ◽  
Author(s):  
Antti Larjo ◽  
Robert Eveleigh ◽  
Elina Kilpeläinen ◽  
Tony Kwan ◽  
Tomi Pastinen ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Hla Typing ◽  
Ensemble Prediction ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
Peptide Antigens ◽  
Hla Genes ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data

AbstractThe human leukocyte antigen (HLA) genes code for proteins that play a central role in the function of the immune system by presenting peptide antigens to T cells. As HLA genes show extremely high genetic polymorphism, HLA typing on the allele level is demanding and is based on DNA sequencing. Determination of HLA alleles is warranted as many HLA alleles are major genetic factors that confer susceptibility to autoimmune diseases and is important for the matching of HLA alleles in transplantation. Here, we compared the accuracy of several published HLA-typing algorithms that are based on next generation sequencing (NGS) data. As genome screens are becoming increasingly routine in research, we wanted to test how well HLA alleles can be deduced from genome screens not designed for HLA typing. The accuracies were assessed using datasets consisting of NGS data produced using the ImmunoSEQ platform, including the full 4 Mbp HLA segment, from 94 stem cell transplantation patients and exome sequences from the 1000 Genomes collection. When used with the default settings none of the methods gave perfect results for all the genes and samples. However, we found that ensemble prediction of the results or modifications of the settings could be used to improve accuracy. Most of the algorithms did not perform very well for the exome-only data. The results indicate that the use of these algorithms for accurate HLA allele determination based on NGS data is not straightforward.

scholarly journals Neolithic genomes reveal a distinct ancient HLA allele pool and population transformation in Europe

2019 ◽  
Author(s):  
Alexander Immel ◽  
Christoph Rinne ◽  
John Meadows ◽  
Rodrigo Barquera ◽  
András Szolek ◽  
...  
Keyword(s):  
Western Europe ◽  
Viral Infections ◽  
Human Leukocyte ◽  
Neolithic Period ◽  
Late Neolithic ◽  
Leukocyte Antigen ◽  
Cultural Transformations ◽  
Farming Community ◽  
Genome Wide ◽  
A Genome

AbstractThe Wartberg culture (WBC, 3,500-2,800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We perform a genome-wide analysis of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3,300-3,200 cal. BCE). Our results highlight that the Niedertiefenbach population indeed emerged at the beginning of the WBC. This farming community was genetically heterogeneous and carried a surprisingly large hunter-gatherer ancestry component (40%). We detect considerable differences in the human leukocyte antigen gene pool between contemporary Europeans and the Niedertiefenbach individuals whose immune response was primarily geared towards defending viral infections.

scholarly journals Protective effects of HLA-DRB1*04 subtypes in Parkinson's and Alzheimer's diseases implicate acetylated Tau PHF6 sequences

2021 ◽  
Author(s):  
Yann Le Guen ◽  
Guo Luo ◽  
Aditya Ambati ◽  
Vincent Damotte ◽  
Iris Jansen ◽  
...  
Keyword(s):  
Adaptive Immune Response ◽  
Human Leukocyte ◽  
Postmortem Brain ◽  
Neuritic Plaque ◽  
Protective Effects ◽  
Hla Association ◽  
Leukocyte Antigen ◽  
Genome Wide ◽  
Association Data ◽  
Lateral Sclerosis

Using genome-wide association data, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's (PD) or Alzheimer's (AD) disease versus controls across ancestry groups. A shared genetic association was observed across diseases at rs601945 (PD: odds ratio (OR)=0.84; 95% confidence interval, [0.80; 0.88]; p=2.2x10-13; AD: OR=0.91[0.89; 0.93]; p=1.8x10-22), and with a protective HLA association recently reported in amyotrophic lateral sclerosis (ALS). Hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03, and absent for HLA-DRB1*04:05. The same signal was associated with decreased neurofibrillary tangles (but not neuritic plaque density) in postmortem brain and was more strongly associated with Tau levels than Aβ42 levels in the cerebrospinal fluid. Finally, protective HLA-DRB1*04 subtypes strongly bound aggregation-prone Tau PHF6 sequence, but only when acetylated at K311, a modification central to aggregation. A HLA-DRB1*04-mediated adaptive immune response, potentially against Tau, decreases PD, AD and ALS risk, offering the possibility of new therapeutic avenues.

scholarly journals HAPDeNovo: a haplotype-based approach for filtering and phasing de novo mutations in linked read sequencing data

2017 ◽  
Author(s):  
Xin Zhou ◽  
Serafim Batzoglou ◽  
Arend Sidow ◽  
Lu Zhang
Keyword(s):  
False Positive ◽  
De Novo ◽  
False Positives ◽  
Sequencing Data ◽  
De Novo Mutations ◽  
Congenital Diseases ◽  
Genome Wide ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data ◽  
Haplotype Information

AbstractBackgroundDe novo mutations (DNMs) are associated with neurodevelopmental and congenital diseases, and their detection can contribute to understanding disease pathogenicity. However, accurate detection is challenging because of their small number relative to the genome-wide false positives in next generation sequencing (NGS) data. Software such as DeNovoGear and TrioDeNovo have been developed to detect DNMs, but at good sensitivity they still produce many false positive calls.ResultsTo address this challenge, we develop HAPDeNovo, a program that leverages phasing information from linked read sequencing, to remove false positive DNMs from candidate lists generated by DNM-detection tools. Short reads from each phasing block are allocated to each of the two haplotypes followed by generating a haploid genotype for each putative DNM.HAPDeNovo removes variants that are called as heterozygous in one of the haplotypes because they are almost certainly false positives. Our experiments on 10X Chromium linked read sequencing trio data reveal that HAPDeNovo eliminates 80% to 99% of false positives regardless of how large the candidate DNM set is.ConclusionsHAPDeNovo leverages the haplotype information from linked read sequencing to remove spurious false positive DNMs effectively, and it increases accuracy of DNM detection dramatically without sacrificing sensitivity.

scholarly journals SweHLA: the high confidence HLA typing bio-resource drawn from 1000 Swedish genomes

2019 ◽  
Vol 28 (5) ◽  
pp. 627-635 ◽  
Author(s):  
Jessika Nordin ◽  
Adam Ameur ◽  
Kerstin Lindblad-Toh ◽  
Ulf Gyllensten ◽  
Jennifer R. S. Meadows
Keyword(s):  
Human Leukocyte ◽  
Class Ii ◽  
Hla Typing ◽  
Class I ◽  
Sequencing Data ◽  
High Confidence ◽  
Leukocyte Antigen ◽  
Hla Dqa1 ◽  
Inference Methods ◽  
Ngs Data

AbstractThere is a need to accurately call human leukocyte antigen (HLA) genes from existing short-read sequencing data, however there is no single solution that matches the gold standard of Sanger sequenced lab typing. Here we aimed to combine results from available software programs, minimizing the biases of applied algorithm and HLA reference. The result is a robust HLA population resource for the published 1000 Swedish genomes, and a framework for future HLA interrogation. HLA 2nd-field alleles were called using four imputation and inference methods for the classical eight genes (class I: HLA-A, HLA-B, HLA-C; class II: HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1). A high confidence population set (SweHLA) was determined using an n−1 concordance rule for class I (four software) and class II (three software) alleles. Results were compared across populations and individual programs benchmarked to SweHLA. Per gene, 875 to 988 of the 1000 samples were genotyped in SweHLA; 920 samples had at least seven loci called. While a small fraction of reference alleles were common to all software (class I = 1.9% and class II = 4.1%), this did not affect the overall call rate. Gene-level concordance was high compared to European populations (>0.83%), with COX and PGF the dominant SweHLA haplotypes. We noted that 15/18 discordant alleles (delta allele frequency >2) were previously reported as disease-associated. These differences could in part explain across-study genetic replication failures, reinforcing the need to use multiple software solutions. SweHLA demonstrates a way to use existing NGS data to generate a population resource agnostic to individual HLA software biases.

Development of a Web-based Program for the Identification of Human Leukocyte Antigen Antibody Specificities

2007 ◽  
Vol 27 (6) ◽  
pp. 458-463 ◽  
Author(s):  
Choong-Hwan Cha ◽  
Heung-Bum Oh ◽  
Myeong Hee Kim ◽  
Jeong-Min Chae ◽  
SoonYoung Jung
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Web Based ◽  
Leukocyte Antigen ◽  
Antibody Specificities ◽  
Antigen Antibody
Sign in / Sign up

Export Citation Format

Share Document