Biology subjects

Jabado-Michaloud, J.

Publications and source records attributed to Jabado-Michaloud, J..

5 recordsLinked to original sources

bioRxiv2025

Characterization of Immunoglobulin Loci in Pongo abelii and Pongo pygmaeus: Insights from Multi-Genome Annotation and IMGT-Based Curation

Antibodies, or immunoglobulins (IG), are central to the vertebrate adaptive immune system, yet the genomic architecture of IG loci remains poorly characterized in many nonhuman primates. In this study we present the first comprehensive genomic analysis of the immunoglobulin (IG) loci (IGH, IGL, and IGK) in two critically endangered orangutan species; Pongo abelii (Sumatran orangutan) and Pongo pygmaeus (Bornean orangutan) across multiple genome assemblies. Using IMGT-standardized biocuration framework combined with read-level structural validation, we identified previously undocumented haplotype-specific variation, including multigene duplications, asymmetric gene absence, and species-specific expansions of variable gene families. Recombination signal sequence (RSS) and switch region analyses revealed conserved regulatory motifs with potential implications for V(D)J recombination and class-switch recombination. These findings underscore the complexity and evolutionary adaptability of IG loci in great apes and highlight the value of orangutans as key references for understanding immune system evolution in the Hominidae lineage.

immunology↗

bioRxiv2025

Novel Genes and Polymorphisms in Human Immunoglobulin Light Chains Across Diverse Populations Through Comprehensive IMGT(R) Analysis

The human immunoglobulin light chain loci, kappa (IGK) and lambda (IGL), are structurally complex genomic regions with germline gene content that is not yet fully characterized. These loci are marked by extensive gene duplication, allelic diversity, and segmental duplications, features that contribute critically to the adaptive immune response. In this study, we present a comprehensive IMGT annotation of IGK and IGL using two high-quality human reference assemblies (GRCh38 and T2T-CHM13) along with 142 and 125 additional chromosomal-level haploid assemblies, respectively for each locus, from individuals representing all major human superpopulations. Detailed gene and allele annotation of the reference assemblies led to the identification of 5 novel IGKV genes and 8 new IGKV alleles, 16 new IGLV genes, and 22 novel IGLV alleles. These were confirmed through assembly read validation, presence in whole genome sequencing datasets, and recurrence in multiple assemblies. Gene-level identification across the broader dataset enabled assessment of structural variation (SV) at both loci. IGL displayed high conservation, with recurrent absence observed for only one gene. In contrast, IGK exhibited greater variability, including complete loss of the distal region in certain assemblies. This structural diversity was analyzed across superpopulations, allowing us to map potential patterns of gene presence and absence across different ancestral groups. All newly identified genes were consistently observed across individuals and genomic backgrounds. This work enhances the structural resolution of the IGK and IGL loci and expands the IMGT reference directory with newly described germline genes and alleles. The results provide a more complete view of light chain genomic diversity and serve as a valuable resource for studies of antibody gene repertoires, immunogenetic variation, monoclonal antibody development and population-level diversity.

genomics↗

bioRxiv2025

IMGT(R) at scale: FAIR, Dynamic and Automated Tools for Immune Locus Analysis

IMGT(R), the international ImMunoGeneTics information system(R), has advanced its comprehensive platform for the analysis of immunoglobulin (IG) and T cell receptor (TR) genes through the development of new automated and scalable tools. This article presents major updates aligned with IMGTs three axes of research. Axis I introduces dynamic resources such as IMGT/GeneTables, IMGT/AssemblyComparison, and IMGT/StatAssembly, enabling real-time access to annotated genomic data and quality assessment of assemblies. Axis II enhances repertoire analysis with a redesigned IMGT/GeneFrequency tool and new customization features in IMGT/V-QUEST, supporting flexible exploration of IG and TR gene expression. Axis III improves the accurate prediction of peptide-MHC thanks to IMGT/RobustpMHC. Additionally, the IMGT Knowledge Graph (IMGT-KG) and its therapeutic extension, IMGT/mAb-KG, provide semantically structured access to more than 100 million immunogenetic triplets, integrating IMGT databases and linking IMGT content to external biomedical resources. These developments promote standardization, interoperability, and integrative analysis across immunogenetics and clinical applications, reinforcing IMGTs role as a core reference in the era of FAIR data and personalized medicine.

bioinformatics↗

bioRxiv2025

IMGT(R) Analysis of the Human IGH Locus: Unveiling Novel Polymorphisms and Copy Number Variations in Genome Assemblies from Diverse Ancestral Backgrounds

Unraveling the genetic complexity of the human immunoglobulin heavy chain (IGH) locus provides valuable insights into the mechanisms underlying the efficacy and specificity of the adaptive immune response. Despite its crucial role, the IGH locus remains insufficiently characterized, with its allelic diversity and polymorphisms inadequately investigated. In this study, we present an analysis of the human IGH locus, incorporating 15 human genome assemblies from diverse ancestries, including African, European, Asian, Saudi, and mixed backgrounds. Through our examination of both maternal and paternal assemblies, we uncover novel IGH alleles, copy number variations (CNV), and polymorphisms, particularly within the variable (IGHV) region. Our findings reveal extensive and previously uncharacterized genetic variability in the constant (IGHC) region and distinct IMGT CNV forms across individuals. This research contributes to a significant enrichment of the IMGT(R) IGH reference directory, databases, tools and web resources and lays the groundwork for a comprehensive IMGT(R) haplotype database which can be progressively enriched to support future studies in population-specific immune profiles and adaptive immune related disease susceptibility, as comprehensive datasets become available. Such a resource promises to propel personalized immunogenomics forward, with exciting applications in cancer immunotherapy, COVID-19, and other immune-related diseases. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/665479v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@17afc2corg.highwire.dtl.DTLVardef@141d785org.highwire.dtl.DTLVardef@1ac7500org.highwire.dtl.DTLVardef@13558fc_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2024

Deciphering of Gorilla gorilla gorilla Immunoglobulin Loci in Multiple Genome Assemblies and Enrichment of IMGT Resources

Through the analysis of immunoglobulin genes at the IGH, IGK, and IGL loci from four Gorilla gorilla gorilla genome assemblies, IMGT(R) provides an in-depth overview of these loci and their individual variations in a species closely related to humans. The similarity between gorilla and human IG gene organization allowed the assignment of gorilla IG gene names based on their human counterparts. This study revealed significant findings, including variability in the IGH locus, the presence of known and new copy number variations (CNVs), and the accurate estimation of IGHG genes. The IGK locus displayed remarkable homogeneity and lacked the gene duplication seen in humans, while the IGL locus showed a previously unconfirmed CNV in the J-C cluster. The curated data from these analyses, available on the IMGT website, enhance our understanding of gorilla immunogenetics and provide valuable insights into primate evolution.

genomics↗