Inferred Allele Review Sub-committee (IARC)

Purpose:

The Inferred Allele Review Sub-committee was formed after the third AIRR-Community meeting in Rockville, MD in December 2017. The IARC is responsible for judging the validity of germline immunoglobulin and TCR genes, inferred from RepSeq data. It advises IMGT and the IUIS/IMGT nomenclature committee of their findings. It also reviews inferred sequences, and evidence in support of their existence, and makes this data available to the AIRR community and other researchers through the OGRDB database. The work of the committee initially focused on human IGHV germline genes, but it is hoped that work will commence on the evaluation of other germline genes, and species.

Achievements:

Begun collating data for inferred human IGHV alleles from interested researchers, and established a formal submission process.
Developed criteria for the review and acceptance of inferred IGHV alleles.
With William Lees and Adrian Shepherd of Birkbeck, University of London, co-developed OGRDB, a public resource for the submission, review and publication of previously unknown receptor germline sequences together with supporting evidence.
In its first year of operation, 16 new IGHV alleles were approved by the IARC. All 16 sequences were subsequently given names by IUIS/IMGT Nomenclature Committee, and have been incorporated into the IMGT Reference Directory.

Further details, including evidence in support of the inferences, can be found at the OGRDB website.

Goals for 2019/2020

The IARC members will work with the Germline Gene Database Working Group to develop policies for the evaluation of inferred new human IGKV and IGLV alleles.

The IARC members will also work with the Germline Gene Database Working Group to develop policies for the evaluation of inferred new human TCR genes, with an initial focus on TRBV sequences.

Although the IARC intends to confine its deliberations to human sequences, members of the IARC will work with other members of the Germline Gene Database Working Group to establish processes and policies for the evaluation of sequences from non-human species. In 2020 it is expected that this initiative will focus on the house mouse, macaque and salmonid species.

Members:

Co-leader: Andrew Collins

Members: Andrew Collins (Co-lead), Martin Corcoran, William Lees, Mats Ohlin, and Cathrine Scheepers.

Related Resources:

The OGRDB database documents the evaluation process of each submitted gene sequence, and provides access to evidence in support of affirmed inferences.

The VDJbase database of genotypes and haplotypes is being developed in association with OGRDB, and provides evidence of the expression of germline genes in hundreds of individuals.

Discussion of some issues arising from activities of the Germline Database Working Group can be found at the B-T.CR Wiki.