title: Computational identification of CDR3 sequence archetypes among immunoglobulin sequences in chronic lymphocytic leukemia.
abstract: The leukemia cells of unrelated patients with chronic lymphocytic leukemia (CLL) display a restricted repertoire of immunoglobulin (Ig) gene rearrangements with preferential usage of certain Ig gene segments. We developed a computational method to rigorously quantify biases in Ig sequence similarity in large patient databases and to identify groups of patients with unusual levels of sequence similarity. We applied our method to sequences from 1577 CLL patients through the CLL Research Consortium (CRC), and identified 67 similarity groups into which roughly 20% of all patients could be assigned. Immunoglobulin light chain class was highly correlated within all groups and light chain gene usage was similar within sets. Surprisingly, over 40% of the identified groups were composed of somatically mutated genes. This study significantly expands the evidence that antigen selection shapes the Ig repertoire in CLL.
authors.affiliation: The Rebecca and John Moores Cancer Center, University of California, San Diego, CA, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Messmer
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Raphael
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Aerni
authors.forename: George F
authors.initials: GF
authors.lastname: Widhopf
authors.forename: Laura Z
authors.initials: LZ
authors.lastname: Rassenti
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
mesh_terms: D001483:Base Sequence; D022801:Complementarity Determining Regions; D019295:Computational Biology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*
chemical_list: D022801:Complementarity Determining Regions