Structurally Mapping Antibody Repertoires

Every human possesses millions of distinct antibodies. It is now possible to analyze this diversity via next-generation sequencing of immunoglobulin genes (Ig-seq). This technique produces large volume sequence snapshots of B-cell receptors that are indicative of the antibody repertoire. In this pap...

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Main Authors: Konrad Krawczyk, Sebastian Kelm, Aleksandr Kovaltsuk, Jacob D. Galson, Dominic Kelly, Johannes Trück, Cristian Regep, Jinwoo Leem, Wing K. Wong, Jaroslaw Nowak, James Snowden, Michael Wright, Laura Starkie, Anthony Scott-Tucker, Jiye Shi, Charlotte M. Deane
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.01698/full
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author Konrad Krawczyk
Sebastian Kelm
Aleksandr Kovaltsuk
Jacob D. Galson
Dominic Kelly
Johannes Trück
Johannes Trück
Cristian Regep
Jinwoo Leem
Wing K. Wong
Jaroslaw Nowak
James Snowden
Michael Wright
Laura Starkie
Anthony Scott-Tucker
Jiye Shi
Charlotte M. Deane
author_facet Konrad Krawczyk
Sebastian Kelm
Aleksandr Kovaltsuk
Jacob D. Galson
Dominic Kelly
Johannes Trück
Johannes Trück
Cristian Regep
Jinwoo Leem
Wing K. Wong
Jaroslaw Nowak
James Snowden
Michael Wright
Laura Starkie
Anthony Scott-Tucker
Jiye Shi
Charlotte M. Deane
author_sort Konrad Krawczyk
collection DOAJ
description Every human possesses millions of distinct antibodies. It is now possible to analyze this diversity via next-generation sequencing of immunoglobulin genes (Ig-seq). This technique produces large volume sequence snapshots of B-cell receptors that are indicative of the antibody repertoire. In this paper, we enrich these large-scale sequence datasets with structural information. Enriching a sequence with its structural data allows better approximation of many vital features, such as its binding site and specificity. Here, we describe the structural annotation of antibodies pipeline that maps the outputs of large Ig-seq experiments to known antibody structures. We demonstrate the viability of our protocol on five separate Ig-seq datasets covering ca. 35 m unique amino acid sequences from ca. 600 individuals. Despite the great theoretical diversity of antibodies, we find that the majority of sequences coming from such studies can be reliably mapped to an existing structure.
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spelling doaj.art-47fb86b0ffff496db413cd8995409a662022-12-22T02:48:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01698387101Structurally Mapping Antibody RepertoiresKonrad Krawczyk0Sebastian Kelm1Aleksandr Kovaltsuk2Jacob D. Galson3Dominic Kelly4Johannes Trück5Johannes Trück6Cristian Regep7Jinwoo Leem8Wing K. Wong9Jaroslaw Nowak10James Snowden11Michael Wright12Laura Starkie13Anthony Scott-Tucker14Jiye Shi15Charlotte M. Deane16Department of Statistics, Oxford University, Oxford, United KingdomUCB Pharma, Slough, United KingdomDepartment of Statistics, Oxford University, Oxford, United KingdomDivision of Immunology, Children’s Research Center, University Children’s Hospital, Zurich, SwitzerlandDivision of Immunology, Children’s Research Center, University Children’s Hospital, Zurich, SwitzerlandDivision of Immunology, Children’s Research Center, University Children’s Hospital, Zurich, SwitzerlandOxford Vaccine Group, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, United KingdomDepartment of Statistics, Oxford University, Oxford, United KingdomDepartment of Statistics, Oxford University, Oxford, United KingdomDepartment of Statistics, Oxford University, Oxford, United KingdomDepartment of Statistics, Oxford University, Oxford, United KingdomUCB Pharma, Slough, United KingdomUCB Pharma, Slough, United KingdomUCB Pharma, Slough, United KingdomUCB Pharma, Slough, United KingdomUCB Pharma, Slough, United KingdomDepartment of Statistics, Oxford University, Oxford, United KingdomEvery human possesses millions of distinct antibodies. It is now possible to analyze this diversity via next-generation sequencing of immunoglobulin genes (Ig-seq). This technique produces large volume sequence snapshots of B-cell receptors that are indicative of the antibody repertoire. In this paper, we enrich these large-scale sequence datasets with structural information. Enriching a sequence with its structural data allows better approximation of many vital features, such as its binding site and specificity. Here, we describe the structural annotation of antibodies pipeline that maps the outputs of large Ig-seq experiments to known antibody structures. We demonstrate the viability of our protocol on five separate Ig-seq datasets covering ca. 35 m unique amino acid sequences from ca. 600 individuals. Despite the great theoretical diversity of antibodies, we find that the majority of sequences coming from such studies can be reliably mapped to an existing structure.https://www.frontiersin.org/article/10.3389/fimmu.2018.01698/fullantibody specificityB-cell receptornext-generation sequencingstructural homologyproteinbioinformatics tools
spellingShingle Konrad Krawczyk
Sebastian Kelm
Aleksandr Kovaltsuk
Jacob D. Galson
Dominic Kelly
Johannes Trück
Johannes Trück
Cristian Regep
Jinwoo Leem
Wing K. Wong
Jaroslaw Nowak
James Snowden
Michael Wright
Laura Starkie
Anthony Scott-Tucker
Jiye Shi
Charlotte M. Deane
Structurally Mapping Antibody Repertoires
Frontiers in Immunology
antibody specificity
B-cell receptor
next-generation sequencing
structural homology
protein
bioinformatics tools
title Structurally Mapping Antibody Repertoires
title_full Structurally Mapping Antibody Repertoires
title_fullStr Structurally Mapping Antibody Repertoires
title_full_unstemmed Structurally Mapping Antibody Repertoires
title_short Structurally Mapping Antibody Repertoires
title_sort structurally mapping antibody repertoires
topic antibody specificity
B-cell receptor
next-generation sequencing
structural homology
protein
bioinformatics tools
url https://www.frontiersin.org/article/10.3389/fimmu.2018.01698/full
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