A5018874456- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Immunodeficiency and Autoimmune Disorders
- Mast cells and histamine
- Food Allergy and Anaphylaxis Research
- Chronic Lymphocytic Leukemia Research
- Blood groups and transfusion
- Allergic Rhinitis and Sensitization
- Physics of Superconductivity and Magnetism
- Electrochemical Analysis and Applications
- Asthma and respiratory diseases
- Analytical Chemistry and Sensors
- RNA and protein synthesis mechanisms
- Urban Transport and Accessibility
- Spectroscopy and Quantum Chemical Studies
- Lymphoma Diagnosis and Treatment
- Advanced Condensed Matter Physics
- Single-cell and spatial transcriptomics
- Theoretical and Computational Physics
- Quantum many-body systems
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Galectins and Cancer Biology
UNSW Sydney
2015-2024
The University of Sydney
2001-2021
University of Bristol
2017
Translational Research Institute
2013
The University of Queensland
2013
University of Bath
2008-2012
Stanford University
2010
Oklahoma Medical Research Foundation
2007
Bipar
2002
St George Hospital
2001
Individual variation in the Ig germline gene repertoire leads to individual differences combinatorial diversity of Ab repertoire, but study such has been problematic. The application high-throughput DNA sequencing rearranged genes now makes this possible. thousands VDJ rearrangements from an individual, either genomic or expressed mRNA, should allow their IGHV, IGHD, and IGHJ repertoires be inferred. In addition, where previously mere glimpses could gained studies, new large data sets...
A model of murine IgG function is presented in which the co‐expression subclasses a central feature, class switching occurs before commencement somatic hypermutation, and there little between subclasses. It named quartet to emphasize harmony that comes from simultaneous presence four In this model, IgG3 IgG2b antibodies are particularly important early response, when T‐cell help may be limiting. initiates inflammation through complement fixation, whereas provides FcγR‐mediated effector...
The diversity of the human antibody repertoire that is generated by V(D)J gene rearrangement extended nine constant region genes give antibodies their complex array effector functions. application high throughput sequencing to study rearrangements has led significant recent advances in our understanding antigen-binding repertoire. In contrast, function changed little, and mystery still surrounds existence four distinctive IgG subclasses. Recent observations from murine models studies VDJ...
Abstract Analysis of antibody repertoires by high-throughput sequencing is major importance in understanding adaptive immune responses. Our knowledge variations the genomic loci encoding immunoglobulin genes incomplete, resulting conflicting VDJ gene assignments and biased genotype haplotype inference. Haplotypes can be inferred using IGHJ6 heterozygosity, observed one third people. Here, we propose a robust novel method for determining haplotypes adapting Bayesian framework. extends...
High-throughput sequencing (HTS) of immunoglobulin (B-cell receptor, antibody) and T-cell receptor repertoires has increased dramatically since the technique was introduced in 2009 [1-3]. This experimental approach explores maturation adaptive immune system its response to antigens, pathogens disease conditions exquisite detail. It holds significant promise for diagnostic therapy-guiding applications. New technology often spreads rapidly, sometimes more rapidly than understanding how make...
Analysis of an individual's immunoglobulin (IG) gene repertoire requires the use high-quality germline reference sets. When sets only contain alleles supported by strong evidence, AIRR sequencing (AIRR-seq) data analysis is more accurate and studies evolution IG genes, their allelic variants expressed immune therefore facilitated.
Abstract Motivation: Immunoglobulin heavy chain (IGH) genes in mature B lymphocytes are the result of recombination IGHV, IGHD and IGHJ germline genes, followed by somatic mutation. The correct identification that make up a variable VH domain is essential to our understanding process antibody diversity generation as well clinical investigations some leukaemias lymphomas. Results: We have developed iHMMune-align, an alignment program uses hidden Markov model (HMM) processes involved human IGH...
The existence of many highly similar genes in the lymphocyte receptor gene loci makes them difficult to investigate, and determination phased "haplotypes" has been particularly problematic. However, V(D)J rearrangements provide an opportunity infer association Ig along chromosomes. chromosomal distribution H chain genotype can be inferred through analysis VDJ individuals who are heterozygous at points within IGH locus. We analyzed from 44 for whom sufficient unique were available allow...
The human and mouse antibody repertoires are formed by identical processes, but like all small animals, mice only have sufficient lymphocytes to express a part of the potential repertoire. In this study, we determined how heavy chain two strains generated. Analysis IgM- IgG-associated VDJ rearrangements generated high-throughput sequencing confirmed presence 99 functional immunoglobulin variable (IGHV) genes in C57BL/6 genome, inferred 164 IGHV BALB/c genome. Remarkably, five sequences were...
Somatic point mutations provide glimpses into B‐cell histories, and mutation numbers generally correlate with antibody affinity. We recently proposed a model of human isotype function, based in part on analysis, which the dominant pathway switching involves B cells moving sequentially through four immunoglobulin (Ig) G subclasses. This should result predictable differences affinity between isotypes, this helps explain how different isotypes work together. The built analysis rearranged heavy...
Abstract Background T and B cell receptor (TCR, BCR) repertoires constitute the foundation of adaptive immunity. Adaptive immune repertoire sequencing (AIRR-seq) is a common approach to study system dynamics. Understanding genetic factors influencing composition dynamics these major scientific clinical importance. The chromosomal loci encoding for variable regions TCRs BCRs are challenging decipher due repetitive elements undocumented structural variants. Methods To confront this challenge,...
VDJbase is a publicly available database that offers easy searching of data describing the complete sets gene sequences (genotypes and haplotypes) inferred from adaptive immune receptor repertoire sequencing datasets. designed to act as resource will allow scientific community explore genetic variability immunoglobulin (Ig) T cell (TR) loci. It can also assist in investigation Ig- TR-related predispositions diseases. Our includes web-based query online tools visualization analysis genotype...
Abstract High-throughput sequencing of the adaptive immune receptor repertoire (AIRR-seq) is providing unprecedented insights into response to disease and development disorders. The accurate interpretation AIRR-seq data depends on existence comprehensive germline gene reference sets. Current sets are known be incomplete unrepresentative degree polymorphism diversity in human animal populations. A key issue complexity genomic regions which they lie, which, because presence multiple repeats,...
The identification of the genes that make up rearranged immunoglobulin is critical to many studies. For example, enumeration mutations in important for prognosis chronic lymphocytic leukemia, and this requires accurate germline from which a particular sequence derived. heavy‐chain variable (IGHV) gene repertoire generally considered be highly polymorphic. In report, we describe bioinformatic analysis sequences casts doubt on existence substantial proportion reported polymorphisms. We report...
Abstract In adaptive immune receptor repertoire analysis, determining the germline variable (V) allele associated with each T- and B-cell sequence is a crucial step. This process highly impacted by annotations. Aligning sequences, assigning them to specific alleles, inferring individual genotypes are challenging when mutated, or reads do not cover whole V region. Here, we propose an alternative naming scheme for as well novel method infer genotypes. We demonstrate strengths of two comparing...