title: Clinical applications of next-generation sequencing in histocompatibility and transplantation.
abstract: OBJECTIVE
  Next-generation sequencing (NGS) can overcome traditional methodological barriers to facilitate detailed studies of large genomes. Here, we summarize recent NGS-based developments in histocompatibility and transplantation, and highlight the dynamic range of clinical applications achievable on this platform.
  
  
  RESULTS
  Multiple NGS-based protocols have been established to achieve unambiguous human leukocyte antigen genotyping. These methods are presently engaged to serve the high-throughput demand of large bone marrow registries; however, the scalable nature of NGS makes it an equally attractive technology for select applications within solid organ transplantation. Recently, the exquisite sensitivity of NGS has been leveraged to perform noninvasive allograft monitoring by tracking the dynamics of donor-derived cell-free DNA. Further, NGS-based T-cell receptor and immunoglobulin heavy chain repertoire profiling appear to be useful in clarifying disease-specific diagnoses in certain complex allograft pathology; detecting/quantifying minimal residual disease following allogeneic stem cell transplantation; and tracking donor-reactive T cells to understand the mechanism of tolerance in kidney transplant recipients.
  
  
  CONCLUSIONS
  NGS is superior to classical Sanger sequencing in its throughput, sensitivity, and the ability to provide phase-defined sequence data. These unique properties allow its broad application to diverse areas in clinical transplantation.
authors.affiliation: aDepartment of Pathology & Laboratory Medicine, UCLA Immunogenetics Center, Los Angeles, California, USA bUniversity of British Columbia Clinician Investigator Program, Vancouver, British Columbia, Canada.
authors.forename: James H
authors.initials: JH
authors.lastname: Lan
authors.forename: Qiuheng
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation; D059014:High-Throughput Nucleotide Sequencing; D006648:Histocompatibility; D006801:Humans; D007108:Immune Tolerance; D016377:Organ Transplantation