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A Broad Survey and Functional Analysis of Immunoglobulin Loci Variation in Rhesus Macaques

Peres, Ayelet ; Upadhyay, Amit A ; Klein, Vered Hana ; Saha, Swati ; Rodriguez, Oscar L ; Vanwinkle, Zachary M ; Karunakaran, Kirti ; Metz, Amanda ; Lauer, William and Lin, Mark C , et al. (2025) In bioRxiv : the preprint server for biology
Abstract

Rhesus macaques (RMs) are a vital model for studying human disease and invaluable to pre-clinical vaccine research, particularly for the study of broadly neutralizing antibody responses. Such studies require robust genetic resources for antibody-encoding genes within the immunoglobulin (IG) loci. The complexity of the IG loci has historically made them challenging to characterize accurately. To address this, we developed novel experimental and computational methodologies to generate the largest collection to date of integrated antibody repertoire and long-read genomic sequencing data in 106 Indian origin RMs. We created a comprehensive resource of IG heavy and light chain variable (V), diversity (D), and joining (J) alleles, as well as... (More)

Rhesus macaques (RMs) are a vital model for studying human disease and invaluable to pre-clinical vaccine research, particularly for the study of broadly neutralizing antibody responses. Such studies require robust genetic resources for antibody-encoding genes within the immunoglobulin (IG) loci. The complexity of the IG loci has historically made them challenging to characterize accurately. To address this, we developed novel experimental and computational methodologies to generate the largest collection to date of integrated antibody repertoire and long-read genomic sequencing data in 106 Indian origin RMs. We created a comprehensive resource of IG heavy and light chain variable (V), diversity (D), and joining (J) alleles, as well as leader, intronic, and recombination signal sequences (RSSs), including the curation of 1474 novel alleles, unveiling tremendous diversity, and expanding existing IG allele sets by 60%. This publicly available, continually updated resource (https://vdjbase.org/reference_book/Rhesus_Macaque) provides the foundation for advancing RM immunogenomics, vaccine discovery, and translational research.

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@misc{480b85db-e122-4529-8bf1-e8760c9c4872,
  abstract     = {{<p>Rhesus macaques (RMs) are a vital model for studying human disease and invaluable to pre-clinical vaccine research, particularly for the study of broadly neutralizing antibody responses. Such studies require robust genetic resources for antibody-encoding genes within the immunoglobulin (IG) loci. The complexity of the IG loci has historically made them challenging to characterize accurately. To address this, we developed novel experimental and computational methodologies to generate the largest collection to date of integrated antibody repertoire and long-read genomic sequencing data in 106 Indian origin RMs. We created a comprehensive resource of IG heavy and light chain variable (V), diversity (D), and joining (J) alleles, as well as leader, intronic, and recombination signal sequences (RSSs), including the curation of 1474 novel alleles, unveiling tremendous diversity, and expanding existing IG allele sets by 60%. This publicly available, continually updated resource (https://vdjbase.org/reference_book/Rhesus_Macaque) provides the foundation for advancing RM immunogenomics, vaccine discovery, and translational research.</p>}},
  author       = {{Peres, Ayelet and Upadhyay, Amit A and Klein, Vered Hana and Saha, Swati and Rodriguez, Oscar L and Vanwinkle, Zachary M and Karunakaran, Kirti and Metz, Amanda and Lauer, William and Lin, Mark C and Melton, Timothy and Granholm, Lukas and Polak, Pazit and Peterson, Samuel M and Peterson, Eric J and Raju, Nagarajan and Shields, Kaitlyn and Schultze, Steven and Ton, Thang and Ericsen, Adam and Lapp, Stacey A and Villinger, Francois J and Ohlin, Mats and Cottrell, Christopher and Amara, Rama Rao and Derdeyn, Cynthia A and Crotty, Shane and Schief, William and Karlsson Hedestam, Gunilla B and Smith, Melissa and Lees, William and Watson, Corey T and Yaari, Gur and Bosinger, Steven E}},
  issn         = {{2692-8205}},
  language     = {{eng}},
  month        = {{03}},
  note         = {{Preprint}},
  publisher    = {{bioRxiv}},
  series       = {{bioRxiv : the preprint server for biology}},
  title        = {{A Broad Survey and Functional Analysis of Immunoglobulin Loci Variation in Rhesus Macaques}},
  url          = {{http://dx.doi.org/10.1101/2025.01.07.631319}},
  doi          = {{10.1101/2025.01.07.631319}},
  year         = {{2025}},
}