Background Over the past few years, next-generation sequencing technologies have been developed to characterize ‘adaptive immune receptor repertoires’ (i.e., antibody/B-cell and T-cell receptor repertoires or AIRRs) in exquisite detail. AIRR sequencing (AIRR-seq) has enormous promise for understanding the dynamics of the immune repertoire in vaccinology, infectious diseases, autoimmunity, and cancer biology. While AIRR-seq data is important, it is also very large, complex, and requires specialized tools and services to curate, analyze, and share. In response to these challenges, The AIRR Community was formed in 2015 (www.airr-community.org). The AIRR Community comprises immunologists, immunogeneticists, computer scientists, bioinformaticians, and experts in legal, ethics and IP issues who are developing shared protocols and standards to facilitate sharing and analysis of these repertoire data through the AIRR Data Commons (ADC).
Methods The iReceptor Gateway (www. ireceptor.org) implements the AIRR Data Commons as a network of federated repositories which facilitates data queries and advanced analyses. Secure data repositories, single cell immune profiling, and RNA gene expression and more detailed cell phenotype data for Systems Immunology are being added by the iReceptor Plus consortium, funded by Canadian Institutes of Health Research (CIHR) and the EU Horizon 2020 program.
Results As of August 2020, the iReceptor Gateway provides access to 2.7 billion receptor sequences, from 2779 repertoires, and 46 studies; these include 3 B-cell and 10 T-cell cancer studies. These can be queried for specific CDR3 sequences, in order to test whether particular sequences are public (occurring in multiple patients) or private (only found in a few individuals). These can also be queried for specific ‘metadata’, e.g. ‘find all repertoires from studies of ovarian cancer.’ The Gateway aggregates these repertoire data for further analysis by sophisticated AIRR-seq algorithms on HPC resources.
Conclusions Analysis of aggregated AIRR-seq data through the iReceptor Gateway has great potential to revolutionize many aspects of cancer immunotherapy. The FDA has already approved the use of AIRR-seq data for monitoring clonal expansion as a diagnostic tool in MRD (minimal residual disease). Sequences from tumor specific clones provide targets for monoclonal antibodies in anti-checkpoint therapy and CAR-T cell approaches. Several studies have shown that AIRR-seq data provide biomarkers that partition patients into responders/non-responders and predict those who may exhibit adverse reactions to novel cancer immunotherapies. This potential will be realized as more researchers adopt the AIRR Community standards for sharing and analyzing AIRR-seq data, resulting in more efficient biomedical research and improved patient care.
Acknowledgements Funded by the European Union’s H2020 Research and Innovation Programme under Grant Agreement No. 825821 and Canadian Institutes of Health Research (CIHR)
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