The Inferred Allele Review Sub-committee (IARC) 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 AIRR-Seq and genomic data and submitting their findings to the IUIS T-cell Receptor and Immunoglobulin Nomenclature Review Committee. 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. Overall, the IARC aims to generate resources for and advocate for better practice in and understanding of IG and TR annotation and analysis in the community interested in studies of AIRR.
Achievements
- Began 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.
- OGRDB has been integrated with VDJbase to simplify submission of VDJbase inferred alleles.
- 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 2022-24
- Affirmation of additional novel human IGHV, IGKV, IGLV, and TRV alleles and extension of partial genes
- Identification of expressed AIRR alleles and publication of human IGV germline allele sets (in collaboration with other WGs)
- Consolidation of a macaque IG germline set by providing expertise to other WGs/IARCs
- Consolidation of the use of temporary labels in instances where formal gene assignment of alleles cannot be made with confidence (in collaboration with other WGs)
- Further integration of genomic and transcriptomic data of genes and alleles of IG loci
- Establishment of processes for allele submission and germline gene sets of other species to OGRDB (in collaboration with other WGs)
- Submission of manuscript(s) on novel alleles and IARC processes
- Publication of guidelines for the generation and growth of germline sets to establish formally recognized gene sets
- Establishment of funding mechanisms moving forward
- Consolidation of the human TCR IARC process
- Development IARC sustainability.
Members
Co-leader: Mats Ohlin
Members: Andrew Collins, Martin Corcoran, James Heather, William Lees, Mats Ohlin (Co-lead), Ayelet Peres, Corey Watson and Gur Yaari.
Products
- 9 inferred immunoglobulin alleles submitted to and approved by IUIS
- A published commentary on the use of short read sequencing for AIRR allele discovery
- A submitted manuscript on Balb/c germline alleles identified by inference (co-authored with other WGs)
- Germline gene sets for Balb/c and C57BL/6 mouse strains published on OGRDB
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.
