Advanced Methodologies in High-Throughput Sequencing of Immune Repertoires.
In recent years, major efforts have been made to develop sophisticated experimental and bioinformatic workflows for sequencing adaptive immune repertoires. The immunological insight gained has been applied to fields as varied as lymphocyte biology, immunodiagnostics, vaccines, cancer immunotherapy, and antibody engineering. In this review, we provide a detailed overview of these advanced methodologies, focusing specifically on strategies to reduce sequencing errors and bias and to achieve high-throughput pairing of variable regions (e.g., heavy-light or alpha-beta chains). In addition, we highlight recent technologies for single-cell transcriptome sequencing that can be integrated with immune repertoires. Finally, we provide a perspective on advanced immune repertoire sequencing and its ability to impact basic immunology, biopharmaceutical drug discovery and development, and cancer immunotherapy.
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Simon
S
Friedensohn
Pharmaceutical Development & Supplies Biologics Europe, F. Hoffman-La Roche Ltd, Basel, Switzerland.
Tarik A
TA
Khan
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. Electronic address: sai.reddy@ethz.ch.
Sai T
ST
Reddy
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology; D019295:Computational Biology / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D017422:Sequence Analysis, DNA / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods; D059010:Single-Cell Analysis / Q000379:methods; D014612:Vaccines / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D014612:Vaccines
B cell receptor; T cell receptor; antibody; immunoglobulin; next-generation sequencing