powerTCR: A model-based approach to comparative analysis of the clone size distribution of the T cell receptor repertoire

PLoS Comput Biol. 2018 Nov 28;14(11):e1006571. doi: 10.1371/journal.pcbi.1006571. eCollection 2018 Nov.

Abstract

Sequencing of the T cell receptor (TCR) repertoire is a powerful tool for deeper study of immune response, but the unique structure of this type of data makes its meaningful quantification challenging. We introduce a new method, the Gamma-GPD spliced threshold model, to address this difficulty. This biologically interpretable model captures the distribution of the TCR repertoire, demonstrates stability across varying sequencing depths, and permits comparative analysis across any number of sampled individuals. We apply our method to several datasets and obtain insights regarding the differentiating features in the T cell receptor repertoire among sampled individuals across conditions. We have implemented our method in the open-source R package powerTCR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Brain Neoplasms / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • Clone Cells
  • Cluster Analysis
  • Computer Simulation
  • Glioblastoma / metabolism
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Immune System*
  • Likelihood Functions
  • Lung / metabolism
  • Mice
  • Programming Languages
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics*
  • Sarcoidosis / metabolism
  • Software

Substances

  • Receptors, Antigen, T-Cell