Inferred Allelic Variants of Immunoglobulin Receptor Genes

A System for Their Evaluation, Documentation, and Naming

Mats Ohlin, Cathrine Scheepers, Martin Corcoran, William D. Lees, Christian E. Busse, Davide Bagnara, Linnea Thörnqvist, Jean Philippe Bürckert, Katherine J.L. Jackson, Duncan Ralph, Chaim A. Schramm, Nishanth Marthandan, Felix Breden, Jamie Scott, Frederick A. Matsen Iv, Victor Greiff, Gur Yaari, Steven H. Kleinstein, Scott Christley, Jacob S. Sherkow & 5 others Sofia Kossida, Marie Paule Lefranc, Menno C. van Zelm, Corey T. Watson, Andrew M. Collins

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement. Existing reference databases are incomplete, as shown by recent AIRR-seq studies that have inferred the existence of many previously unreported polymorphisms. Completing the documentation of genetic variation in germline gene databases is therefore of crucial importance. Lymphocyte receptor genes and alleles are currently assigned by the Immunoglobulins, T cell Receptors and Major Histocompatibility Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS) and managed in IMGT®, the international ImMunoGeneTics information system® (IMGT). In 2017, the IMGT Group reached agreement with a group of AIRR-seq researchers on the principles of a streamlined process for identifying and naming inferred allelic sequences, for their incorporation into IMGT®. These researchers represented the AIRR Community, a network of over 300 researchers whose objective is to promote all aspects of immunoglobulin and T-cell receptor repertoire studies, including the standardization of experimental and computational aspects of AIRR-seq data generation and analysis. The Inferred Allele Review Committee (IARC) was established by the AIRR Community to devise policies, criteria, and procedures to perform this function. Formalized evaluations of novel inferred sequences have now begun and submissions are invited via a new dedicated portal (https://ogrdb.airr-community.org). Here, we summarize recommendations developed by the IARC-focusing, to begin with, on human IGHV genes-with the goal of facilitating the acceptance of inferred allelic variants of germline IGHV genes. We believe that this initiative will improve the quality of AIRR-seq studies by facilitating the description of human IG germline gene variation, and that in time, it will expand to the documentation of TR and IG genes in many vertebrate species.

Original languageEnglish
Article number435
Number of pages13
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 18 Mar 2019

Keywords

  • AIRR-seq
  • allelic variation
  • IGHV
  • immunoglobulin
  • inference
  • V(D)J rearrangement

Cite this

Ohlin, M., Scheepers, C., Corcoran, M., Lees, W. D., Busse, C. E., Bagnara, D., ... Collins, A. M. (2019). Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming. Frontiers in Immunology, 10, [435]. https://doi.org/10.3389/fimmu.2019.00435
Ohlin, Mats ; Scheepers, Cathrine ; Corcoran, Martin ; Lees, William D. ; Busse, Christian E. ; Bagnara, Davide ; Thörnqvist, Linnea ; Bürckert, Jean Philippe ; Jackson, Katherine J.L. ; Ralph, Duncan ; Schramm, Chaim A. ; Marthandan, Nishanth ; Breden, Felix ; Scott, Jamie ; Matsen Iv, Frederick A. ; Greiff, Victor ; Yaari, Gur ; Kleinstein, Steven H. ; Christley, Scott ; Sherkow, Jacob S. ; Kossida, Sofia ; Lefranc, Marie Paule ; van Zelm, Menno C. ; Watson, Corey T. ; Collins, Andrew M. / Inferred Allelic Variants of Immunoglobulin Receptor Genes : A System for Their Evaluation, Documentation, and Naming. In: Frontiers in Immunology. 2019 ; Vol. 10.
@article{e0c23347847841acaf86815781198190,
title = "Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming",
abstract = "Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement. Existing reference databases are incomplete, as shown by recent AIRR-seq studies that have inferred the existence of many previously unreported polymorphisms. Completing the documentation of genetic variation in germline gene databases is therefore of crucial importance. Lymphocyte receptor genes and alleles are currently assigned by the Immunoglobulins, T cell Receptors and Major Histocompatibility Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS) and managed in IMGT{\circledR}, the international ImMunoGeneTics information system{\circledR} (IMGT). In 2017, the IMGT Group reached agreement with a group of AIRR-seq researchers on the principles of a streamlined process for identifying and naming inferred allelic sequences, for their incorporation into IMGT{\circledR}. These researchers represented the AIRR Community, a network of over 300 researchers whose objective is to promote all aspects of immunoglobulin and T-cell receptor repertoire studies, including the standardization of experimental and computational aspects of AIRR-seq data generation and analysis. The Inferred Allele Review Committee (IARC) was established by the AIRR Community to devise policies, criteria, and procedures to perform this function. Formalized evaluations of novel inferred sequences have now begun and submissions are invited via a new dedicated portal (https://ogrdb.airr-community.org). Here, we summarize recommendations developed by the IARC-focusing, to begin with, on human IGHV genes-with the goal of facilitating the acceptance of inferred allelic variants of germline IGHV genes. We believe that this initiative will improve the quality of AIRR-seq studies by facilitating the description of human IG germline gene variation, and that in time, it will expand to the documentation of TR and IG genes in many vertebrate species.",
keywords = "AIRR-seq, allelic variation, IGHV, immunoglobulin, inference, V(D)J rearrangement",
author = "Mats Ohlin and Cathrine Scheepers and Martin Corcoran and Lees, {William D.} and Busse, {Christian E.} and Davide Bagnara and Linnea Th{\"o}rnqvist and B{\"u}rckert, {Jean Philippe} and Jackson, {Katherine J.L.} and Duncan Ralph and Schramm, {Chaim A.} and Nishanth Marthandan and Felix Breden and Jamie Scott and {Matsen Iv}, {Frederick A.} and Victor Greiff and Gur Yaari and Kleinstein, {Steven H.} and Scott Christley and Sherkow, {Jacob S.} and Sofia Kossida and Lefranc, {Marie Paule} and {van Zelm}, {Menno C.} and Watson, {Corey T.} and Collins, {Andrew M.}",
year = "2019",
month = "3",
day = "18",
doi = "10.3389/fimmu.2019.00435",
language = "English",
volume = "10",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media",

}

Ohlin, M, Scheepers, C, Corcoran, M, Lees, WD, Busse, CE, Bagnara, D, Thörnqvist, L, Bürckert, JP, Jackson, KJL, Ralph, D, Schramm, CA, Marthandan, N, Breden, F, Scott, J, Matsen Iv, FA, Greiff, V, Yaari, G, Kleinstein, SH, Christley, S, Sherkow, JS, Kossida, S, Lefranc, MP, van Zelm, MC, Watson, CT & Collins, AM 2019, 'Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming', Frontiers in Immunology, vol. 10, 435. https://doi.org/10.3389/fimmu.2019.00435

Inferred Allelic Variants of Immunoglobulin Receptor Genes : A System for Their Evaluation, Documentation, and Naming. / Ohlin, Mats; Scheepers, Cathrine; Corcoran, Martin; Lees, William D.; Busse, Christian E.; Bagnara, Davide; Thörnqvist, Linnea; Bürckert, Jean Philippe; Jackson, Katherine J.L.; Ralph, Duncan; Schramm, Chaim A.; Marthandan, Nishanth; Breden, Felix; Scott, Jamie; Matsen Iv, Frederick A.; Greiff, Victor; Yaari, Gur; Kleinstein, Steven H.; Christley, Scott; Sherkow, Jacob S.; Kossida, Sofia; Lefranc, Marie Paule; van Zelm, Menno C.; Watson, Corey T.; Collins, Andrew M.

In: Frontiers in Immunology, Vol. 10, 435, 18.03.2019.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - Inferred Allelic Variants of Immunoglobulin Receptor Genes

T2 - A System for Their Evaluation, Documentation, and Naming

AU - Ohlin, Mats

AU - Scheepers, Cathrine

AU - Corcoran, Martin

AU - Lees, William D.

AU - Busse, Christian E.

AU - Bagnara, Davide

AU - Thörnqvist, Linnea

AU - Bürckert, Jean Philippe

AU - Jackson, Katherine J.L.

AU - Ralph, Duncan

AU - Schramm, Chaim A.

AU - Marthandan, Nishanth

AU - Breden, Felix

AU - Scott, Jamie

AU - Matsen Iv, Frederick A.

AU - Greiff, Victor

AU - Yaari, Gur

AU - Kleinstein, Steven H.

AU - Christley, Scott

AU - Sherkow, Jacob S.

AU - Kossida, Sofia

AU - Lefranc, Marie Paule

AU - van Zelm, Menno C.

AU - Watson, Corey T.

AU - Collins, Andrew M.

PY - 2019/3/18

Y1 - 2019/3/18

N2 - Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement. Existing reference databases are incomplete, as shown by recent AIRR-seq studies that have inferred the existence of many previously unreported polymorphisms. Completing the documentation of genetic variation in germline gene databases is therefore of crucial importance. Lymphocyte receptor genes and alleles are currently assigned by the Immunoglobulins, T cell Receptors and Major Histocompatibility Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS) and managed in IMGT®, the international ImMunoGeneTics information system® (IMGT). In 2017, the IMGT Group reached agreement with a group of AIRR-seq researchers on the principles of a streamlined process for identifying and naming inferred allelic sequences, for their incorporation into IMGT®. These researchers represented the AIRR Community, a network of over 300 researchers whose objective is to promote all aspects of immunoglobulin and T-cell receptor repertoire studies, including the standardization of experimental and computational aspects of AIRR-seq data generation and analysis. The Inferred Allele Review Committee (IARC) was established by the AIRR Community to devise policies, criteria, and procedures to perform this function. Formalized evaluations of novel inferred sequences have now begun and submissions are invited via a new dedicated portal (https://ogrdb.airr-community.org). Here, we summarize recommendations developed by the IARC-focusing, to begin with, on human IGHV genes-with the goal of facilitating the acceptance of inferred allelic variants of germline IGHV genes. We believe that this initiative will improve the quality of AIRR-seq studies by facilitating the description of human IG germline gene variation, and that in time, it will expand to the documentation of TR and IG genes in many vertebrate species.

AB - Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement. Existing reference databases are incomplete, as shown by recent AIRR-seq studies that have inferred the existence of many previously unreported polymorphisms. Completing the documentation of genetic variation in germline gene databases is therefore of crucial importance. Lymphocyte receptor genes and alleles are currently assigned by the Immunoglobulins, T cell Receptors and Major Histocompatibility Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS) and managed in IMGT®, the international ImMunoGeneTics information system® (IMGT). In 2017, the IMGT Group reached agreement with a group of AIRR-seq researchers on the principles of a streamlined process for identifying and naming inferred allelic sequences, for their incorporation into IMGT®. These researchers represented the AIRR Community, a network of over 300 researchers whose objective is to promote all aspects of immunoglobulin and T-cell receptor repertoire studies, including the standardization of experimental and computational aspects of AIRR-seq data generation and analysis. The Inferred Allele Review Committee (IARC) was established by the AIRR Community to devise policies, criteria, and procedures to perform this function. Formalized evaluations of novel inferred sequences have now begun and submissions are invited via a new dedicated portal (https://ogrdb.airr-community.org). Here, we summarize recommendations developed by the IARC-focusing, to begin with, on human IGHV genes-with the goal of facilitating the acceptance of inferred allelic variants of germline IGHV genes. We believe that this initiative will improve the quality of AIRR-seq studies by facilitating the description of human IG germline gene variation, and that in time, it will expand to the documentation of TR and IG genes in many vertebrate species.

KW - AIRR-seq

KW - allelic variation

KW - IGHV

KW - immunoglobulin

KW - inference

KW - V(D)J rearrangement

UR - http://www.scopus.com/inward/record.url?scp=85064215478&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2019.00435

DO - 10.3389/fimmu.2019.00435

M3 - Review Article

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 435

ER -