Abstract
In this paper we present VDJSeq-Solver, a methodology and tool to identify clonal lymphocyte populations from paired-end RNA Sequencing reads derived from the sequencing of mRNA neoplastic cells. The tool detects the main clone that characterises the tissue of interest by recognizing the most abundant V(D)J rearrangement among the existing ones in the sample under study. The exact sequence of the clone identified is capable of accounting for the modifications introduced by the enzymatic processes. The proposed tool overcomes limitations of currently available lymphocyte rearrangements recognition methods, working on a single sequence at a time, that are not applicable to high-throughput sequencing data. In this work, VDJSeq-Solver has been applied to correctly detect the main clone and identify its sequence on five Mantle Cell Lymphoma samples; then the tool has been tested on twelve Diffuse Large B-Cell Lymphoma samples. In order to comply with the privacy, ethics and intellectual property policies of the University Hospital and the University of Verona, data is available upon request to supporto.utenti@ateneo.univr.it after signing a mandatory Materials Transfer Agreement. VDJSeq-Solver JAVA/Perl/Bash software implementation is free and available at http://eda.polito.it/VDJSeq-Solver/.
Highlights
The B-cells and T-cells of jawed vertebrates possess unique genomes due to structural rearrangements of B-cell receptor (BCR) and T-cell receptor (TCR) for antigens, caused by complex and dynamical rearrangement events involving several variable (V), diversity (D) and joining (J) gene segments [1, 2]
Variable regions of Immunoglobulin Heavy (IGH) and Immunoglobulin Light (IGL) chains of BCR are assembled respectively from germline V, D, J and V, J segments thanks to a site-specific reaction called V (D)J recombination that involves the developing of B lymphocytes [3, 4]
Based on Next-Generation Sequencing (NGS) technology, we identify clonal lymphocyte populations by quantifying the amount of RNA expressed by the gene segments rearranged in the neoplastic clone with respect to the total amount of RNA expressed by the other BCR gene segments
Summary
The B-cells and T-cells of jawed vertebrates possess unique genomes due to structural rearrangements of B-cell receptor (BCR) and T-cell receptor (TCR) for antigens, caused by complex and dynamical rearrangement events involving several variable (V), diversity (D) and joining (J) gene segments [1, 2]. The combinatorial diversity that comes from the different rearrangements of the V, D and J germlines is further improved by the diversification of the junction between the three segments during the V(D)J recombination This process is characterised by the introduction of nucleotides by the Terminal deoxynucleotidyl Transferase (TdT) [5] that follows the deletion of nucleotides at the 3’ end of the V gene segment, at the 5’ end of the J gene segment, and at both the ends of the D gene segment which recombine. In absence of this last process very short inverted sequences, called palindromic-regions, can be found at the V(D)J junction
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