Jan 25, 2016

Statistics of Cellular Evolution in Leukemia: Allelic Variations in Patient Trajectories Based on Immune Repertoire Sequencing

BioRxiv : the Preprint Server for Biology
Hong GaoWenzhong Xiao

Abstract

The evolution of a cancer system consisting of cancer clones and normal cells is a complex dynamic process with multiple interacting factors including clonal expansion, somatic mutation, and sequential selection. As a typical example, in patients with chronic lymphocytic leukemia (CLL), a monoclonal population of transformed B cells expands to dominate the B cell population in the peripheral blood and bone marrow. This expansion of transformed B cells suggests that they might evolve through processes distinct from those of normal B cells. Recent advances in next generation sequencing enable the high-throughput identification and tracking of individual B cell clones through sequencing of the V-D-J junction segments of the immunoglobulin heavy chain (IGH). Here we developed a statistical approach to modeling cellular evolution of the immune repertoire. Adapting the infinitely many alleles model from population genetics, we studied abnormalities occurring in the immune repertoire of patients as substantial deviations from the null model. The Ewens sampling test (EST) distinguished the immune repertoires of CLL patients with imminent relapse from healthy controls and patients in sustained remission. Extensive simulations based on s...Continue Reading

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Mentioned in this Paper

M Protein, multiple myeloma
Normal Cell
Peripheral Blood
Somatic Mutation
Bone Marrow
Nucleic Acid Sequencing
B-Lymphocytes
Cancer Remission
Cell Growth
Sequencing

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