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

Mathieu Giraud (1, 2) , Mikaël Salson (1, 2) , Marc Duez (3, 1, 2) , Céline Villenet (4) , Sabine Quief (4, 5) , Aurélie Caillault (6) , Nathalie Grardel (6) , Christophe Roumier (6, 7) , Claude Preudhomme (6, 7) , Martin Figeac (4)

1 LIFL - Laboratoire d'Informatique Fondamentale de Lille
2 BONSAI - Bioinformatics and Sequence Analysis
3 SIRIC-ONCOLille - Site de Recherche Intégrée en Cancérologie
4 Plateforme de génomique fonctionnelle et structurelle [Lille]
5 IRCL - Institut pour la recherche sur le cancer de Lille [Lille]
6 Service d'Hématologie Cellulaire [Lille]
7 Institut de recherche sur le cancer

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.

Mots clés: Sequence analysis; High-throughput sequencing; V(D)J recombinations; Repertoire sequencing (Rep-Seq); Immunology; Leukemia; Minimal residual disease follow-up

Domaines: Bio-informatique [q-bio.QM]; Bio-Informatique, Biologie Systémique [q-bio.QM]; Génétique; Immunologie; Bibliothèque électronique [cs.DL]

Mathieu Giraud, Mikaël Salson, Marc Duez, Céline Villenet, Sabine Quief, et al.. Fast multiclonal clusterization of V(D)J recombinations from high-throughput sequencing. BMC Genomics, 2014, 15 (1), pp.409. ⟨10.1186/1471-2164-15-409⟩. ⟨hal-01009173⟩