Mosaic deletion patterns of the human antibody heavy chain gene locus shown by Bayesian haplotyping

Moriah Gidoni; Omri Snir; Ayelet Peres; Pazit Polak; Ida Lindeman; Ivana Mikocziova; Vikas Kumar Sarna; Knut E.A. Lundin; Christopher Clouser; Francois Vigneault; Andrew M. Collins; Ludvig M. Sollid; Gur Yaari

doi:10.1038/s41467-019-08489-3

Mosaic deletion patterns of the human antibody heavy chain gene locus shown by Bayesian haplotyping

Moriah Gidoni, Omri Snir, Ayelet Peres, Pazit Polak, Ida Lindeman, Ivana Mikocziova, Vikas Kumar Sarna, Knut E.A. Lundin, Christopher Clouser, Francois Vigneault, Andrew M. Collins, Ludvig M. Sollid, Gur Yaari

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62 Scopus citations

Abstract

Analysis of antibody repertoires by high-throughput sequencing is of major importance in understanding adaptive immune responses. Our knowledge of variations in the genomic loci encoding immunoglobulin genes is incomplete, resulting in conflicting VDJ gene assignments and biased genotype and haplotype inference. Haplotypes can be inferred using IGHJ6 heterozygosity, observed in one third of the people. Here, we propose a robust novel method for determining VDJ haplotypes by adapting a Bayesian framework. Our method extends haplotype inference to IGHD- and IGHV-based analysis, enabling inference of deletions and copy number variations in the entire population. To test this method, we generated a multi-individual data set of naive B-cell repertoires, and found allele usage bias, as well as a mosaic, tiled pattern of deleted IGHD and IGHV genes. The inferred haplotypes may have clinical implications for genetic disease predispositions. Our findings expand the knowledge that can be extracted from antibody repertoire sequencing data.

Original language	English
Article number	628
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-08489-3
State	Published - 7 Feb 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

Funding

This research was supported by grants from ISF (grant number 832/16) to G.Y., P.P., A.P. and M.G. and grants from the Research Council of Norway through its Centre of Excellence funding scheme (project number 179573/V40), the South-Eastern Norway Regional Health Authority (project 2016113) and Stiftelsen KG Jebsen (SKGMED-017) to L.M.S.

Funders	Funder number
Stiftelsen Kristian Gerhard Jebsen	SKGMED-017
Israel Science Foundation	832/16
Norges Forskningsråd	179573/V40
Helse Sør-Øst RHF	2016113

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Gidoni, M., Snir, O., Peres, A., Polak, P., Lindeman, I., Mikocziova, I., Sarna, V. K., Lundin, K. E. A., Clouser, C., Vigneault, F., Collins, A. M., Sollid, L. M., & Yaari, G. (2019). Mosaic deletion patterns of the human antibody heavy chain gene locus shown by Bayesian haplotyping. Nature Communications, 10(1), Article 628. https://doi.org/10.1038/s41467-019-08489-3

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abstract = "Analysis of antibody repertoires by high-throughput sequencing is of major importance in understanding adaptive immune responses. Our knowledge of variations in the genomic loci encoding immunoglobulin genes is incomplete, resulting in conflicting VDJ gene assignments and biased genotype and haplotype inference. Haplotypes can be inferred using IGHJ6 heterozygosity, observed in one third of the people. Here, we propose a robust novel method for determining VDJ haplotypes by adapting a Bayesian framework. Our method extends haplotype inference to IGHD- and IGHV-based analysis, enabling inference of deletions and copy number variations in the entire population. To test this method, we generated a multi-individual data set of naive B-cell repertoires, and found allele usage bias, as well as a mosaic, tiled pattern of deleted IGHD and IGHV genes. The inferred haplotypes may have clinical implications for genetic disease predispositions. Our findings expand the knowledge that can be extracted from antibody repertoire sequencing data.",

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Mosaic deletion patterns of the human antibody heavy chain gene locus shown by Bayesian haplotyping

Abstract

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