The Repertoire Dissimilarity Index as a method to compare lymphocyte receptor repertoires

BMC Bioinformatics

Methodology Article

Florian Rubelt¹  Christopher R. Bolen²  Mark M. Davis³  Jason A. Vander Heiden⁴ 

[1] Department of Microbiology and Immunology, Stanford University School of Medicine, 94305, Stanford, CA, USA;Department of Microbiology and Immunology, Stanford University School of Medicine, 94305, Stanford, CA, USA;Genentech, Inc., 1 DNA Way, MS 93, 94080, South San Francisco, CA, USA;Department of Microbiology and Immunology, Stanford University School of Medicine, 94305, Stanford, CA, USA;Howard Hughes Medical Institute, Stanford University School of Medicine, 94305, Stanford, CA, USA;Institute of Immunity, Department of Microbiology and Immunology, Transplantation and Infection, Stanford University School of Medicine, 94305, Stanford, CA, USA;Interdepartmental Program in Computational Biology and Bioinformatics, Department of Computational Biology & Bioinformatics, Yale University, 06520, New Haven, CT, USA;

关键词: Repertoire sequencing;    Immunology;    Nonparametric methods;   

DOI  :  10.1186/s12859-017-1556-5

 received in 2016-10-29, accepted in 2017-02-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe B and T cells of the human adaptive immune system leverage a highly diverse repertoire of antigen-specific receptors to protect the human body from pathogens. The sequencing and analysis of immune repertoires is emerging as an important tool to understand immune responses, whether beneficial or harmful (in the case of autoimmunity). However, methods for studying these repertoires, and for directly comparing different immune repertoires, are lacking.ResultsIn this paper, we present a non-parametric method for directly comparing sequencing repertoires, with the goal of rigorously quantifying differences in V, D, and J gene segment utilization. This method, referred to as the Repertoire Dissimilarity Index (RDI), uses a bootstrapped subsampling approach to account for variance in sequencing depth, and, coupled with a data simulation approach, allows for direct quantification of the average variation between repertoires. We use the RDI method to recapitulate known differences in the formation of the CD4+ and CD8+ T cell repertoires, and further show that antigen-driven activation of naïve CD8+ T cells is more selective than in the CD4+ repertoire, resulting in a more specialized CD8+ memory repertoire.ConclusionsWe prove that the RDI method is an accurate and versatile method for comparisons of immune repertoires. The RDI method has been implemented as an R package, and is available for download through Bitbucket.

【 授权许可】

CC BY   
© The Author(s). 2017