Affiliations: Institut de Mathématiques et de Modélisation
de Montpellier, UMR CNRS 5149, Equipe de Probabilités et Statistique,
Université Montpellier II, CC 051, Place Eugène Bataillon, 34095
Montpellier Cedex 5, France. E-mail: {bleakley,biau}@math.univ-montp2.fr | IMGT®, the
international ImMunoGeneTics information
system®, Laboratoire
d'ImmunoGénétique Moléculaire LIGM, UPR CNRS 1142, Institut de
Génétique Humaine IGH, 141 rue de la Cardonille, 34396 Montpellier
Cedex 5, France. E-mail: {Veronique.Giudicelli, Marie-Paule.Lefranc,Yan.Wu}@igh.cnrs.fr | Institut Universitaire de France
Abstract: The diversity of immunoglobulin (IG) and T cell receptor (TR) chains
depends on several mechanisms: combinatorial diversity, which is a consequence
of the number of V, D and J genes and the N-REGION diversity, which creates an
extensive and clonal somatic diversity at the V-J and V-D-J junctions. For the
IG, the diversity is further increased by somatic hypermutations. The number of
different junctions per chain and per individual is estimated to be
10^{12}. We have chosen the human TRAV-TRAJ junctions as an
example in order to characterize the required criteria for a standardized
analysis of the IG and TR V-J and V-D-J junctions, based on the IMGT-ONTOLOGY
concepts, and to serve as a first IMGT junction reference set
(IMGT®, http://imgt.cines.fr). We performed
a thorough statistical analysis of 212 human rearranged TRAV-TRAJ sequences,
which were aligned and analysed by the integrated IMGT/V-QUEST software, which
includes IMGT/JunctionAnalysis, then manually expert-verified. Furthermore, we
compared these 212 sequences with 37 other human TRAV-TRAJ junction sequences
for which some particularities (potential sequence polymorphisms, sequencing
errors, etc.) did not allow IMGT/JunctionAnalysis to provide the correct
biological results, according to expert verification. Using statistical
learning, we constructed an automatic warning system to predict if new,
automatically analysed TRAV-TRAJ sequences should be manually re-checked. We
estimated the robustness of this automatic warning system.
