OGRDB: a reference database of inferred immune receptor genes.

William Lees,Cathrine Scheepers,Christian E Busse,Martin Corcoran,Gur Yaari,Frederick A Matsen,Corey T Watson,Andrew Collins,Mats Ohlin,Adrian J Shepherd

doi:10.1093/nar/gkz822

Abstract

High-throughput sequencing of the adaptive immune receptor repertoire (AIRR-seq) is providing unprecedented insights into the immune response to disease and into the development of immune disorders. The accurate interpretation of AIRR-seq data depends on the existence of comprehensive germline gene reference sets. Current sets are known to be incomplete and unrepresentative of the degree of polymorphism and diversity in human and animal populations. A key issue is the complexity of the genomic regions in which they lie, which, because of the presence of multiple repeats, insertions and deletions, have not proved tractable with short-read whole genome sequencing. Recently, tools and methods for inferring such gene sequences from AIRR-seq datasets have become available, and a community approach has been developed for the expert review and publication of such inferences. Here, we present OGRDB, the Open Germline Receptor Database (https://ogrdb.airr-community.org), a public resource for the submission, review and publication of previously unknown receptor germline sequences together with supporting evidence.

Highlights

The genes of B-cell and T-cell antigen receptors (IG, TR) lie in some of the most structurally complex and polymorphic regions of vertebrate genomes
On the Sequences tab, OGRDB presents a browsable list of inferred alleles affirmed by the Inferred Allele Review Committees (IARCs) review process, and, where a sequence has been accepted by IMGT, the canonical name allocated by IMGT
Clicking on a sequence name provides a detailed view of the sequence record, including, importantly, the supporting evidence submitted to IARC that underlies the inferred sequence

Summary

Introduction

The genes of B-cell and T-cell antigen receptors (IG, TR) lie in some of the most structurally complex and polymorphic regions of vertebrate genomes. Because of their repetitive nature, the presence of many copy number variants, and the variation between individuals, the IG and TR genomic loci are problematic to study via standard high-throughput genomic approaches. Short-read surveys of human genetic variation such as the 1000 Genomes Project [1] remain challenging to interpret in these loci, to the extent that it is unclear whether such approaches can reliably deliver information on IG and TR germline variation (2, see https://www.internationalgenome.org/faq/whyonly-85-genome-assayable).

Results

Discussion

Conclusion