An open protocol for modeling T Cell Clonotype repertoires using TCRβ CDR3 sequences

Abstract

T cell receptor repertoires can be profiled using next generation sequencing (NGS) to measure and monitor adaptive dynamical changes in response to disease and other perturbations. Genomic DNA-based bulk sequencing is cost-effective but necessitates multiplex target amplification using multiple primer pairs with highly variable amplification efficiencies. Here, we utilize an equimolar primer mixture and propose a single statistical normalization step that efficiently corrects for amplification bias post sequencing. Using samples analyzed by both our open protocol and a commercial solution, we show high concordance between bulk clonality metrics. This approach is an inexpensive and open-source alternative to commercial solutions.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jun 26, 2023
Source ID
10.1186/s12864-023-09424-z

Entities

People

  • Adam A. Margolin
  • Biqing Zhu
  • Burcu Gurun
  • Dhaarini Murugan
  • Katelyn T. Byrne
  • Lisa Coussens
  • Motomi Mori
  • Patrick Leyshock
  • Paul Spellman
  • Robert H. Vonderheide
  • Sushil Kumar
  • Terence P. Speed
  • Wesley Horton

Organizations

  • American Cancer Society
  • National Cancer Institute
  • Stand Up to Cancer
  • Susan G. Komen for the Cure
  • United States Department of Defense

Tags

Fields of Study

  • Biology

Readers

  • Immunology
  • Oncology and Biomarker-Based Cancer Detection.
  • Systems Analysis and Design