Using antibody next generation sequencing to aid antibody engineering
Lead Research Organisation:
University of Oxford
Department Name: Interdisciplinary Bioscience DTP
Abstract
"Antibodies are proteins produced by immune systems of jawed vertebrates that recognize and eliminate pathogenic molecules from the organism. Their binding malleability arises as a result of their great diversity. The estimated total unique human antibody repertoire diversity lies in the range of 1011. The advent of Next Generation Sequencing (NGS) has made it possible to produce snapshots of this diversity. Here we describe our work with a large NGS dataset provided by UCB Pharma comprising 13.5m heavy and light chains from ~500 individuals. By studying this dataset we aim to establish a set of descriptors that will allow us to formally interrogate the properties of within and across species immune repertoires. Furthermore, UCB Pharma have comprehensive NGS datasets across a number of species, including human, mouse, llama and rabbit. Deeper understanding of inter-species antibody ontogeny would highlight commonalities and differences. Such insight can lead to a definition of what construes a 'human' antibody and better understanding of the mechanics of antibody maturation. Thorough analysis of antibody repertoires can shed light on immune system maturation paving the way for improved vaccine design and drug discovery. Mapping of NGS datasets of immunized subjects to the antibody structure space will interrogate cascades of the antibody ontogeny process and aid to create an antibody maturation model.
BBSRC priorities: Bioscience for Health, Data driven biology, New therapeutic approaches to industrial biotechnology, Systems approaches to the bioscienc"
BfH, WCUB, ENWW
BBSRC priorities: Bioscience for Health, Data driven biology, New therapeutic approaches to industrial biotechnology, Systems approaches to the bioscienc"
BfH, WCUB, ENWW
Publications
Kovaltsuk A
(2018)
Observed Antibody Space: A Resource for Data Mining Next-Generation Sequencing of Antibody Repertoires.
in Journal of immunology (Baltimore, Md. : 1950)
Kovaltsuk A
(2017)
How B-Cell Receptor Repertoire Sequencing Can Be Enriched with Structural Antibody Data.
in Frontiers in immunology
Kovaltsuk A
(2020)
Structural diversity of B-cell receptor repertoires along the B-cell differentiation axis in humans and mice.
in PLoS computational biology
Kovaltsuk A
(2018)
Filtering Next-Generation Sequencing of the Ig Gene Repertoire Data Using Antibody Structural Information.
in Journal of immunology (Baltimore, Md. : 1950)
Krawczyk K
(2019)
Looking for therapeutic antibodies in next-generation sequencing repositories.
in mAbs
Krawczyk K
(2018)
Structurally Mapping Antibody Repertoires.
in Frontiers in immunology
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/M011224/1 | 30/09/2015 | 31/03/2024 | |||
1801486 | Studentship | BB/M011224/1 | 30/09/2016 | 29/09/2020 |
Description | I develop the first database that holds more than billion sequences of antibodies generating using next-generation sequencing technologies. There I cleaned, numbered and annotated antibody sequences with metadata. This database is publicly available http://antibodymap.org/oas I also develop a tool that identifies and cleans erroneous sequences in antibody next-generation sequencing datasets. The tool is available for download at http://opig.stats.ox.ac.uk//data/downloads/aboss-1.1.tar.gz In 2020, I have published a research paper in a peer review journal (PLOS Computational Biology). In this paper, we develop a rapid method to structurally characterise immune repertoires in humans. We made this tool open source which is available on github (https://github.com/oxpig/saab_plus). |
Exploitation Route | Researchers from both academia and industry actively use the database that I developed. |
Sectors | Pharmaceuticals and Medical Biotechnology |