How B-Cell Receptor Repertoire Sequencing Can Be Enriched with Structural Antibody Data

@article{Kovaltsuk2017HowBR,
  title={How B-Cell Receptor Repertoire Sequencing Can Be Enriched with Structural Antibody Data},
  author={Aleksandr Kovaltsuk and Konrad Krawczyk and Jacob D. Galson and Dominic F. Kelly and Charlotte M. Deane and Johannes Tr{\"u}ck},
  journal={Frontiers in Immunology},
  year={2017},
  volume={8}
}
Next-generation sequencing of immunoglobulin gene repertoires (Ig-seq) allows the investigation of large-scale antibody dynamics at a sequence level. However, structural information, a crucial descriptor of antibody binding capability, is not collected in Ig-seq protocols. Developing systematic relationships between the antibody sequence information gathered from Ig-seq and low-throughput techniques such as X-ray crystallography could radically improve our understanding of antibodies. The… 
Structurally Mapping Antibody Repertoires
TLDR
The structural annotation of antibodies pipeline is described that maps the outputs of large Ig-seq experiments to known antibody structures and it is found that the majority of sequences coming from such studies can be reliably mapped to an existing structure.
Observed Antibody Space: A Resource for Data Mining Next-Generation Sequencing of Antibody Repertoires
TLDR
This work has collected Ig-seq outputs from 55 studies, covering more than half a billion Ab sequences across diverse immune states, organisms, and individuals, and makes the data available via the Observed Antibody Space (OAS) resource at http://antibodymap.org.
Observed Antibody Space: a resource for data mining next generation sequencing of antibody repertoires
TLDR
This work has collected Ig-seq outputs from 53 studies, covering more than half a billion antibody sequences across diverse immune states, organisms and individuals, and made them available via the Observed Antibody Space (OAS) resource at antibodymap.org.
Characterisation of naïve and antigen-experienced human antibody repertoires
TLDR
High-throughput sequencing and ribosome display are used to investigate the B cell repertoires of recent Ebola survivors to determine how this disease affects the repertoire and to attempt to identify new, cross-reactive, anti-Ebola glycoprotein antibodies.
Filtering Next-Generation Sequencing of the Ig Gene Repertoire Data Using Antibody Structural Information
TLDR
This work describes an orthogonal method for filtering Ig-seq data, which considers the structural viability of each sequence, and shows how ABOSS is able to identify structurally impossible sequences missed by other error-correction methods.
Structural Diversity of B-Cell Receptor Repertoires along the B-cell Differentiation Axis in Humans and Mice
TLDR
It is shown that B-cell types can be distinguished based solely on these structural properties and establish the paratope structure differences in BCR repertoires and have applications for many fields including immunodiagnostics, phage display library generation, and “humanness” assessment of B CR repertoires from transgenic animals.
How repertoire data are changing antibody science
TLDR
The many ways in which BCR repertoire data have been or could be exploited are discussed, highlighting its utility for providing insights into how the naive immune repertoire is generated and how it responds to antigens.
Epitope profiling using computational structural modelling demonstrated on coronavirus-binding antibodies
TLDR
The results show that applying structural analytics to large class-specific antibody databases will enable high confidence structure-function relationships to be drawn, yielding new opportunities to identify functional convergence hitherto missed by sequence-only analysis.
Definition of immunoglobulin germline genes by next generation sequencing for studies of antigen-specific b cell responses
TLDR
The work presented in this thesis establishes a road map to generate individualized immunoglobulin germline gene databases from diverse species, even if genomic immunoglOBulin loci information is limited.
Immunoglobulin gene analysis as a tool for investigating human immune responses
TLDR
The juxtaposition of lymphocyte development and numerical evaluation of immune repertoireires has resulted in the growth of a new sub‐speciality in immunology where immunologists and computer scientists/physicists collaborate to assess immune repertoires and develop models of immune action.
...
...

References

SHOWING 1-10 OF 129 REFERENCES
Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires
TLDR
The data presented in this report provide fundamental new insights regarding the biological features of antibody selection and maturation and establish a benchmark for future studies of antibody responses to disease or to vaccination.
The promise and challenge of high-throughput sequencing of the antibody repertoire
Efforts to determine the antibody repertoire encoded by B cells in the blood or lymphoid organs using high-throughput DNA sequencing technologies have been advancing at an extremely rapid pace and
Application of circular consensus sequencing and network analysis to characterize the bovine IgG repertoire
TLDR
This data indicates that unusually long CDR3 sequences are not unique to IgM antibodies in cattle, and hypothesizes that network or cluster-based analyses of expressed antibody repertoires from controlled challenge experiments will help identify novel natural antigen binding solutions to specific pathogens of interest.
In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire
TLDR
A low-cost, single-cell, emulsion-based technology for sequencing antibody VH-VL repertoires from >2 × 106 B cells per experiment with demonstrated pairing precision >97%.
BCR repertoire sequencing: different patterns of B cell activation after two Meningococcal vaccines
TLDR
High‐throughput B‐cell repertoire sequencing provides a unique insight into patterns of B‐ cell activation not possible from more conventional measures of immunogenicity.
Toward a more accurate view of human B-cell repertoire by next-generation sequencing, unbiased repertoire capture and single-molecule barcoding
TLDR
It is expected that, based upon long-read and high-fidelity next-generation sequencing technologies, the unbiased analysis will provide a more accurate view of the overall antibody repertoire while the barcoding strategy will facilitate high-resolution analysis of individual antibody families.
Clustering-based identification of clonally-related immunoglobulin gene sequence sets
TLDR
This work has developed and implemented an algorithm for identifying sets of clonally-related sequences in large human immunoglobulin heavy chain gene variable region sequence sets and provided a more accurate and considerably faster identification ofClonalRelate gene sequences than visual inspection by domain experts.
...
...