IGLoo: Profiling the Immunoglobulin Heavy chain locus in Lymphoblastoid Cell Lines with PacBio High-Fidelity Sequencing reads

Abstract

AbstractNew high-quality human genome assemblies derived from lymphoblastoid cell lines (LCLs) provide reference genomes and pangenomes for genomics studies. However, the characteristics of LCLs pose technical challenges to profiling immunoglobulin (IG) genes. IG loci in LCLs contain a mixture of germline and somatically recombined haplotypes, making them difficult to genotype or assemble accurately. To address these challenges, we introduceIGLoo, a software tool that implements novel methods for analyzing sequence data and genome assemblies derived from LCLs.IGLoocharacterizes somatic V(D)J recombination events in the sequence data and identifies the breakpoints and missing IG genes in the LCL-based assemblies. Furthermore,IGLooimplements a novel reassembly framework to improve germline assembly quality by integrating information about somatic events and population structural variantions in the IG loci. We appliedIGLooto study the assemblies from the Human Pangenome Reference Consortium, providing new insights into the mechanisms, gene usage, and patterns of V(D)J recombination, causes of assembly fragmentation in the IG heavy chain (IGH) locus, and improved representation of the IGH assemblies.