Biology subjects

Giudicelli, V.

Publications and source records attributed to Giudicelli, V..

9 recordsLinked to original sources

bioRxiv2026

The αβTCR repertoire at scale in the immgenT dataset

The immense T cell receptor (TCR) repertoire is shaped by VDJ combinatorial diversity, imprecise rearrangements, and clonal selection. The immgenT Project generated scRNA and TCRseq to map paired {beta}TCR repertoires across 734 mouse samples from diverse tissues and challenge conditions. Compositional analysis uncovered some extreme junctional architectures. Beyond probabilistic V and J pairing, over-represented joins suggested non-randomness in fine joining, broadening the precedent of quasi-invariant iNKT and MAIT TCRs. We charted public clonotypes linked to self or environmental antigens in the main lineages. Tissue analyses revealed compartmentalized tissue-specific expansions. Unproductive and productive rearrangements of a V gene appeared to interfere specifically with each other, at chromatin or RNA levels. Unexpectedly, allelic exclusion at TCR{beta} proved less stringent than thought, and we identified rearrangements of TCR in immature pre-T stages. This organism-wide look into the TCR repertoire offers novel insights on the evolutionary and immunological pressures on TCR repertoire selection.

immunology↗

bioRxiv2025

Unraveling IGK Locus in Dog Breeds: IMGT(R) New Insights into Canine Immunogenetics.

Over millennia, the selective breeding of dogs (Canis lupus familiaris) has generated remarkable genetic diversity among breeds, highlighting the need for comprehensive genomic and immunogenetic studies. This research provides detailed immunoglobulin kappa light chain locus (IGK) analysis across multiple dog breeds. It aims to uncover breed-specific genetic variations and their implications for immunology and veterinary medicine. The primary objectives were to do the biocuration of the IGK locus in nine canine genome assemblies, investigate structural variations, polymorphisms, and gene diversity, and to enrich the IMGT(R) database with comprehensive IGK data from diverse breeds, creating a more inclusive genetic resource. Our extensive annotation of breeds, including the Bernese Mountain Dog, Boxer, Cairn Terrier, Labrador Retriever, Great Dane, Basenji, and German Shepherd, identified 40 genes and 97 alleles, revealing both conserved genes and unique variants across these breeds, with in silico validation through Sanger sequencing. Notably, we analyzed discrepancies in the first reference assembly from the Boxer breed (Canfam3.1), highlighting potential errors in assembly, challenges in gene and allele nomenclature, and a low-density region within the canine IGK locus. This study not only refines the understanding of IGK locus diversity but also contributes to the IMGT(R) databases, advancing future research on immunogenetic variability, somatic mutations, and immune response dynamics in canine health and disease.

immunology↗

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

Therapeutic Monoclonal Antibodies Repurposing in Oncology via IMGT/mAb-KG Embeddings

BackgroundCancer remains one of the leading causes of mortality world-wide, accounting for approximately 9.7 million deaths in 2022. Faced with this significant public health challenge, therapeutic monoclonal antibodies (mAbs) have emerged as promising alternatives that may minimize the side effects associated with conventional treatments such as radiotherapy and chemotherapy. To support mAb research and development, IMGT(R), the international ImMuno-GeneTics information system, has established two standardized data sources namely IMGT/mAb-DB, a comprehensive database for mAbs, and, more recently, IMGT/mAb-KG, a dedicated knowledge graph for mAbs. Despite these advances, the development of therapeutic mAbs remains both time-consuming and financially burdensome--costs can reach up to $2.8 billion. To address this challenge and accelerate cancer treatment, mAb repurposing represents a promising alternative. ResultsIn this study, we leveraged a subset of IMGT/mAb-KG, dedicated to the oncology domain, to develop a scientific hypothesis generation application for mAb repurposing. This application, based on knowledge graph embedding techniques, is designed to suggest potential mAb candidates for novel oncology applications. A user-friendly web interface provides access to the tool, incorporating visual support to facilitate the interpretation of generated hypotheses. This application is a decision support tool aiming to accelerate the discovery of new therapeutic applications for existing mAbs. ConclusionOur application demonstrates the potential of knowledge graph embedding techniques in the oncology domain by enabling the repurposing of existing mAbs for new therapeutic uses. Using this tool, we have identified two novel mAbs, loncastuximab tesirine and glofitamab, both currently undergoing clinical trials for the treatment of chronic lymphocytic leukemia. This decision-support tool thus facilitates the discovery of new therapeutic opportunities by effectively repositioning existing mAbs for oncological indications, potentially accelerating the development of cancer therapies and addressing critical public health needs.

bioinformatics↗

bioRxiv2025

Identification of Engineered IMGT Fc Variants in IMGT/mAb-DB Therapeutic Antibodies and Fusion proteins

Monoclonal antibodies (mAbs) and fusion proteins for immune applications (FPIA) play a crucial role in treating autoimmune diseases and cancers by targeting cell-surface proteins and triggering multiple immune mechanisms. These functions are mediated by the fragment crystallizable (Fc) region of mAbs and fusion proteins, whose interaction with Fc gamma receptors (Fc{gamma}Rs) can be modulated through Fc amino acid (AA) engineering. To address this, we developed the IMGT/FcVariantsExplorer tool (https://www.imgt.org/fcvariantsexplorer/) to identify AA changes within the Fc region in mAb and fusion proteins sequences from IMGT/2Dstructure-DB, the AA sequence database of IMGT(R), the international ImMunoGeneTics information system(R). We used the IMGT(R) nomenclature of engineered Fc variants involved in antibody effector properties and formats, applying a standardized classification in five categories: Effector, Half-life, Physicochemical properties, Structure, and Hybrid. We analyzed sequences of 1,107 mAbs and fusion proteins, identifying 483 entries with Fc AA changes, resulting in 211 unique Fc variants in the dataset. We also used web scraping to retrieve associated biological data from literature. All data have been integrated into IMGT/mAb-DB, with links to sequences in IMGT/2Dstructure-DB, enabling users to query Fc variants by their Category or Effect. This curated dataset reveals key trends in antibody engineering.

bioinformatics↗

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↗