AIRR community curation and standardised representation for immunoglobulin and T cell receptor germline sets

Abstract

Analysis of an individual's immunoglobulin or T cell receptor gene repertoire can provide important insights into immune function. High-quality analysis of adaptive immune receptor repertoire sequencing data depends upon accurate and relatively complete germline sets, but current sets are known to be incomplete. Established processes for the review and systematic naming of receptor germline genes and alleles require specific evidence and data types, but the discovery landscape is rapidly changing. To exploit the potential of emerging data, and to provide the field with improved state-of-the-art germline sets, an intermediate approach is needed that will allow the rapid publication of consolidated sets derived from these emerging sources. These sets must use a consistent naming scheme and allow refinement and consolidation into genes as new information emerges. Name changes should be minimised, but, where changes occur, the naming history of a sequence must be traceable. Here we outline the current issues and opportunities for the curation of germline IG/TR genes and present a forward-looking data model for building out more robust germline sets that can dovetail with current established processes. We describe interoperability standards for germline sets, and an approach to transparency based on principles of findability, accessibility, interoperability, and reusability.

Keywords: AIRR-seq; Immune receptor; Immune receptor germline; Immune receptor repertoire; Rep-seq.

Fig. 1.

Cumulative number of human IG alleles in IMGT databases (LIGM-DB to 2001 and IMGT GENE/DB subsequently).

Fig. 2.

Alleles inferred from AIRR-seq reads are derived from recombined VDJ sequences, meaning that the exact genes from which they arise (determined by location in the immune receptor locus) cannot be determined. In some cases, the location can be inferred by assessing sequence similarity to genes in the reference genome. However, the presence of multiple highly similar genes may make it impossible to determine the correct mapping unambiguously.

Fig. 3.

Challenges in the characterization of IG/TR genes, and the current status in three key species.

Fig. 4.

Summary of results.

Fig. 5.

(A) – the relationship of objects defined in the Schema. (B) - evolution of labels and aliases through phases of discovery. The diagram depicts four stages in the activity of a community group curating sequences from a particular species. These events are likely to be separated in time and may be triggered by the availability of additional evidence.

Fig. 6.

The AIRR Germline Set Schema. See Supplementary Data for detailed description and itemisation of fields.