Second, deposition into public archives is not uniformly required by journals or funding agencies. First, the storage and transport of such large datasets, which can comprise hundreds of millions of sequences (and hundreds of gigabytes) per study, require substantial time and resources. Several challenges currently impede the effective sharing of AIRR-seq data. Ensuring the reliability of such integrative analyses, however, will require the establishment of and adherence to standards for reporting and sharing data across multiple laboratories and centers. As the number of datasets continues to grow, comparative analyses of hundreds or even thousands of individuals will soon be feasible. AIRR-seq data are increasingly important in the development of vaccines, monoclonal antibodies, cancer immunotherapies, and other applications. HTS of AIRRs (AIRR-seq) is yielding valuable insights into how variation in the AIRR differs across lymphocyte subsets ( 13– 16) and anatomic compartments ( 17– 20), varies over the course of a disease or with therapy ( 21– 27), and is influenced by age ( 28– 32), genetic background ( 33, 34), health status ( 19, 29, 35– 37), antigen exposure ( 27, 38– 40), and other factors. Since HTS was first applied to AIRR profiling in 2009 ( 1, 3, 6, 7), there has been rapid advancement of both experimental and computational techniques. Here, we focus on HTS-based profiling of AIRR. While many immune repertoire studies have been performed using a variety of methods, adequate analysis of the repertoire as a whole was virtually impossible prior to the advent of high-throughput sequencing (HTS). However, a single immunoglobulin or T-cell receptor sequence is but a drop of water in the ocean that is the immune repertoire. These data sets provide important insights into immune receptor–antigen interactions and can inform antibody engineering efforts. Furthermore, there are databases that incorporate or allow viewing of structural data, such as IMGT, IEDB-3D, AntigenDB, and SAbDab. Immunoglobulin and T-cell receptor sequences have been studied for decades and several established databases exist including Kabat–Wu and Vbase2 ( 9, 10). Thus, the collection of B-cell and T-cell receptor variable region genes expressed at any given time-the adaptive immune receptor repertoire (AIRR)-is dynamic. The lymphocytes that express these receptors arise, proliferate, and die on time scales of hours to years ( 1, 8). Humans each express over 100 million unique immunoglobulins ( 6) and a similar number of T-cell receptors ( 1, 7). The variable regions of the adaptive immune receptors on B cells and T cells arise through the rearrangement of germline variable, diversity, and joining gene segments ( 4, 5). Finally, and most important, we invite all interested parties to join this effort to facilitate sharing and use of these powerful data sets ( adaptive immune system provides protection against disease without inducing harmful autoimmunity it reacts against the vast and ever-changing array of pathogens that an individual will encounter over a lifetime, while tolerating self. The purpose of this perspective is to provide an overview of the AIRR Community’s founding principles and present the progress that the AIRR Community has made in developing standards of practice and data sharing protocols. The Adaptive Immune Receptor Repertoire (AIRR) Community formed in 2015 to address similar issues for HTS data of immune repertoires. As complex technologies have developed, scientific communities have come together to adopt common standards, protocols, and policies for generating and sharing data sets, such as the MIAME protocols developed for microarray experiments. New technology often spreads rapidly, sometimes more rapidly than the understanding of how to make the products of that technology reliable, reproducible, or usable by others. It holds significant promise for diagnostic and therapy-guiding applications. This experimental approach explores the maturation of the adaptive immune system and its response to antigens, pathogens, and disease conditions in exquisite detail. High-throughput sequencing (HTS) of immunoglobulin (B-cell receptor, antibody) and T-cell receptor repertoires has increased dramatically since the technique was introduced in 2009 ( 1– 3).
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