High-Throughput Immunogenetics for Clinical and Research Applications in Immunohematology: Potential and Challenges

J Immunol. 2017 May 15;198(10):3765-3774. doi: 10.4049/jimmunol.1602050. Epub 2017 Apr 17.


Analysis and interpretation of Ig and TCR gene rearrangements in the conventional, low-throughput way have their limitations in terms of resolution, coverage, and biases. With the advent of high-throughput, next-generation sequencing (NGS) technologies, a deeper analysis of Ig and/or TCR (IG/TR) gene rearrangements is now within reach, which impacts on all main applications of IG/TR immunogenetic analysis. To bridge the generation gap from low- to high-throughput analysis, the EuroClonality-NGS Consortium has been formed, with the main objectives to develop, standardize, and validate the entire workflow of IG/TR NGS assays for 1) clonality assessment, 2) minimal residual disease detection, and 3) repertoire analysis. This concerns the preanalytical (sample preparation, target choice), analytical (amplification, NGS), and postanalytical (immunoinformatics) phases. Here we critically discuss pitfalls and challenges of IG/TR NGS methodology and its applications in hemato-oncology and immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Computational Biology / methods
  • Gene Rearrangement
  • Genes, Immunoglobulin
  • Genes, T-Cell Receptor / genetics
  • Hematology / methods*
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Immunogenetics / methods*
  • Immunogenetics / standards
  • Immunologic Techniques*