Only those reads for which both the mates have been partially mapped around the D gene segment are considered to create the virtual reference. These reads may fall in two cases: i)The two mates are partially or totally overlapped in the D region (see Fig. 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 house policies of the University or college Hospital and the University or college of Verona, data is usually available upon request to firstname.lastname@example.org after signing a mandatory Materials Transfer Agreement. VDJSeq-Solver JAVA/Perl/Bash software implementation is usually free and Cardiolipin available at http://eda.polito.it/VDJSeq-Solver/. Introduction 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 Cardiolipin (J) gene segments [1, 2]. The antigen receptors on B-cells are multiprotein complexes made up of clonally variable antigen-binding chains called Immunoglobulin (IG) chains associated with the coreceptor CD79A and CD79B proteins. Every chain is usually characterised in its amine-terminus (N-terminal) portion by a variable amino acid sequence that is involved in specific antigen binding and in its carboxy-terminus (C-terminal) region by a constant part that defines the class and effector function of the antibody molecule. Variable regions of Immunoglobulin Heavy (IGH) and Immunoglobulin Light (IGL) chains of BCR are put together 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]. In particular, for what is concerning IGH, several different mechanisms generate the variable region diversity with respect to V(D)J recombination. The combinatorial diversity that comes from the different rearrangements of the V, D and J germlines is usually further improved by the diversification of the junction between the three segments during the V(D)J recombination. This process is indeed characterised by the introduction of nucleotides by the Terminal deoxynucleotidyl Transferase (TdT)  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 ZPK process very short inverted sequences, called palindromic-regions, can be found at the V(D)J junction. This diversity determines the huge variability of interactions possible between antigens and antigen receptors, that is one of the pillars of the adaptive immune response. B-cells and T-cells are therefore different from other cells in the fact that their genomes bear a genomic birthmark of diversity. They can expand under specific conditions (e.g. antigen encounter) and form monoclonal populations bearing identically rearranged gene segments [6, 7]. These clonal populations are usually under tight control mechanisms. However, under special occasions they might expand to an extent which causes a disease, such as in autoimmune disorders, leukemias and lymphomas . Recently different studies have been devoted to the characterisation of the BCRs in different pathologies leading, for example, to the discovery of biases in the usage of specific IGH [9C16] or IGL gene segments [17, 18] with respect to the normal expected distribution and Cardiolipin to the correlation of the clinical course of the disease with the rate of somatic hypermutation of BCR gene segments [19, 20]. PCR-based clonality assessments are nowadays very popular in diagnostic hematopathology, being able to detect abnormal growth of single clonal populations in a normal polyclonal lymphocyte populace. Clonality assessments are however characterised by amazing drawbacks such.