3 research outputs found
IgIDivA : immunoglobulin intraclonal diversification analysis
Intraclonal diversification (ID) within the immunoglobulin (IG) genes expressed by B cell clones arises due to ongoing somatic hypermutation (SHM) in a context of continuous interactions with antigen(s). Defining the nature and order of appearance of SHMs in the IG genes can assist in improved understanding of the ID process, shedding light into the ontogeny and evolution of B cell clones in health and disease. Such endeavor is empowered thanks to the introduction of high-throughput sequencing in the study of IG gene repertoires. However, few existing tools allow the identification, quantification and characterization of SHMs related to ID, all of which have limitations in their analysis, highlighting the need for developing a purpose-built tool for the comprehensive analysis of the ID process. In this work, we present the immunoglobulin intraclonal diversification analysis (IgIDivA) tool, a novel methodology for the in-depth qualitative and quantitative analysis of the ID process from high-throughput sequencing data. IgIDivA identifies and characterizes SHMs that occur within the variable domain of the rearranged IG genes and studies in detail the connections between identified SHMs, establishing mutational pathways. Moreover, it combines established and new graph-based metrics for the objective determination of ID level, combined with statistical analysis for the comparison of ID level features for different groups of samples. Of importance, IgIDivA also provides detailed visualizations of ID through the generation of purpose-built graph networks. Beyond the method design, IgIDivA has been also implemented as an R Shiny web application. IgIDivA is freely available at https://bio.tools/igidiv
P835: IN SILICO PREDICTION REVEALS PUTATIVE T-CELL CLASS I/II NEOEPITOPES WITHIN THE CLONOTYPIC IMMUNOGLOBULIN HEAVY AND LIGHT CHAINS IN PATIENTS WITH MULTIPLE MYELOMA
Chromatin activation profiling of stereotyped chronic lymphocytic leukemias reveals a subset 8-specific signature
The chromatin activation landscape of chronic lymphocytic leukemia (CLL) with stereo-typed B-cell receptor immunoglobulin is currently unknown. In this study, we report the results of a whole-genome chromatin profiling of histone 3 lysine 27 acetylation of 22 CLLs from major subsets, which were compared against nonstereotyped CLLs and normal B-cell subpopulations. Although subsets 1, 2, and 4 did not differ much from their non-stereotyped CLL counterparts, subset 8 displayed a remarkably distinct chromatin acti-vation profile. In particular, we identified 209 de novo active regulatory elements in this subset, which showed similar patterns with U-CLLs undergoing Richter transformation. These regions were enriched for binding sites of 9 overexpressed transcription factors. In 78 of 209 regions, we identified 113 candidate overexpressed target genes, 11 regions being associated with more than 2 adjacent genes. These included blocks of up to 7 genes, suggesting local coupregulation within the same genome compartment. Our findings further underscore the uniqueness of subset 8 CLL, notable for the highest risk of Richter's transformation among all CLLs and provide additional clues to decipher the molecular basis of its clinical behavior