Fast multiclonal clusterization of V(D)J recombinations from high-throughput sequencing

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Giraud, Mathieu | Salson, Mikaël | Duez, Marc | Villenet, Céline | Quief, Sabine | Caillault, Aurélie | Grardel, Nathalie | Roumier, Christophe | Preudhomme, Claude | Figeac, Martin

Edité par CCSD ; BioMed Central -

International audience. BACKGROUND: V(D)J recombinations in lymphocytes are essential for immunological diversity. They are also usefulmarkers of pathologies. In leukemia, they are used to quantify the minimal residual disease duringpatient follow-up. However, the full breadth of lymphocyte diversity is not fully understood. RESULTS: We propose new algorithms that process high-throughput sequencing (HTS) data to extract unnamedV(D)J junctions and gather them into clones for quantification. This analysis is based on a seedheuristic and is fast and scalable because in the first phase, no alignment is performed with germlinedatabase sequences. The algorithms were applied to TR HTS data from a patient with acutelymphoblastic leukemia, and also on data simulating hypermutations. Our methods identified themain clone, as well as additional clones that were not identified with standard protocols. CONCLUSIONS: The proposed algorithms provide new insight into the analysis of high-troughput sequencing data forleukemia, and also to the quantitative assessment of any immunological profile. The methodsdescribed here are implemented in a C++ open-source program called Vidjil.

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