Stem cells 2013 July-16

 

Fractal organization of the human T cell repertoire in health and after stem cell transplantation.

Biol Blood Marrow Transplant. 2013 Mar;19(3):366-77.

Meier J, Roberts C, Avent K, Hazlett A, Berrie J, Payne K, Hamm D, Desmarais C, Sanders C, Hogan KT, Archer KJ, Manjili MH, Toor AA.

Bone Marrow Transplant Program, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.

Abstract

T cell repertoire diversity is generated in part by recombination of variable (V), diversity (D), and joining (J) segments in the T cell receptor β (TCR) locus. T cell clonal frequency distribution determined by high-throughput sequencing of TCR β in 10 stem cell transplantation (SCT) donors revealed a fractal, self-similar frequency distribution of unique TCR bearing clones with respect to V, D, and J segment usage in the T cell repertoire of these individuals. Further, ranking of T cell clones by frequency of gene segment usage in the observed sequences revealed an ordered distribution of dominant clones conforming to a power law, with a fractal dimension of 1.6 and 1.8 in TCR β DJ and VDJ containing clones in healthy stem cell donors. This self-similar distribution was perturbed in the recipients after SCT, with patients demonstrating a lower level of complexity in their TCR repertoire at day 100 followed by a modest improvement by 1 year post-SCT. A large shift was observed in the frequency distribution of the dominant T cell clones compared to the donor, with fewer than one third of the VDJ-containing clones shared in the top 4 ranks. In conclusion, the normal T cell repertoire is highly ordered with a TCR gene segment usage that results in a fractal self-similar motif of pattern repetition across levels of organization. Fractal analysis of high-throughput TCR β sequencing data provides a comprehensive measure of immune reconstitution after SCT. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

PMID: 23313705

 

amir toor

Fractal Organization of the Human T Cell Repertoire.

Amir Ahmed Toor MD. Associate Professor of Medicine, Virginia Commonwealth University, Richmond, VA.

Fractals are mathematical constructs, which demonstrate self-similarity across scales of magnification. Scale invariance of magnitude is modeled by power-law distribution, which may be identified by examining the relationship between logarithm of magnitude and logarithm of a corresponding scaling factor (SF). In fractal constructs this relationship demonstrates a relatively uniform value, termed the fractal-dimension (FD). Fractal structural motifs are widely observed in nature, such as in the branching patterns of trees, or vascular networks in animals. A germ-line linear strand of DNA such as the T cell receptor b locus (TCR) being rearranged to yield millions of unique T cell clones, may be similarly considered. We assigned the number of gene segments used to define T cell clones, specific scaling factor values, and considered the frequency of the TCR b sequences bearing unique diversity, joining (DJ) and variable (VDJ) gene segments, as well as nucleotide insertions (VDJ+NI) with reference to the respective scaling factors. The resulting analysis demonstrated that the T cell repertoire is highly ordered with TCR b gene segment frequency demonstrating self-similarity at multiple levels of clonal definition, with consistent FD values being observed between normal individuals. This analytic insight may yield an improved understanding of large-scale patterns of immune reconstitution in normal individuals and following stem cell transplantation.

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