Biological controls for standardization and interpretation of adaptive immune receptor repertoire profiling

Johannes Trück,Eline T Luning Prak,Christopher M Tipton,Aimee S Payne,Anne Eugster,Cinque Soto,Pierre Barennes,Jacob S Sherkow,Encarnita Mariotti-Ferrandiz,Andrew Farmer,The Airr Community ,Davide Bagnara,Marie-Paule Lefranc,Magnolia Bostick

doi:10.7554/elife.66274

Abstract

Use of adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread, providing new insights into the immune system with potential broad clinical and diagnostic applications. However, like many high-throughput technologies, it comes with several problems, and the AIRR Community was established to understand and help solve them. We, the AIRR Community’s Biological Resources Working Group, have surveyed scientists about the need for standards and controls in generating and annotating AIRR-seq data. Here, we review the current status of AIRR-seq, provide the results of our survey, and based on them, offer recommendations for developing AIRR-seq standards and controls, including future work.

Highlights

Immunoglobulin chains (IG) and T-cell receptor chains (TR) are generated by DNA recombination, a process of somatic rearrangement of variable (V), diversity (D), and joining (J) genesTruck, Eugster, Barennes, et al eLife 2021;10:e66274
next-generation sequencing (NGS)-based approaches and methods have multiplied, including high-throughput bulk sequencing of IG or TR starting from genomic DNA or mRNA, which typically provides information on one receptor chain only, and more recently to the sequencing of the two IG or TR chains expressed in a single cell, which provides information on the antigen-specific receptor
The members of the adaptive immune receptor repertoire (AIRR) Community Biological Resources Working Group (WG) have summarized the current practice regarding the use of standards and controls among its members as well as among other international AIRR-seq experts and in the literature

Summary

Introduction

Immunoglobulin chains (IG) and T-cell receptor chains (TR) are generated by DNA recombination, a process of somatic rearrangement of variable (V), diversity (D), and joining (J) genes. NGS-based approaches and methods have multiplied, including high-throughput bulk sequencing of IG or TR starting from genomic DNA (gDNA) or mRNA (as cDNA), which typically provides information on one receptor chain only, and more recently to the sequencing of the two IG or TR chains expressed in a single cell, which provides information on the antigen-specific receptor. These approaches are increasingly applied, mostly to human AIRRs, and to study AIRRs from other organisms (Chaudhary and Wesemann, 2018; Minervina et al, 2019). Direct combination of AIRR-seq with single-cell immunophenotype (e.g., transcriptome or cell surface protein expression)

Methods

Discussion and future work

Findings

Funding Funder