The CAIRR Pipeline for Submitting Standards-Compliant B and T Cell Receptor Repertoire Sequencing Studies to the National Center for Biotechnology Information Repositories

Abstract

The adaptation of high-throughput sequencing to the B cell receptor and T cell receptor has made it possible to characterize the adaptive immune receptor repertoire (AIRR) at unprecedented depth. These AIRR sequencing (AIRR-seq) studies offer tremendous potential to increase the understanding of adaptive immune responses in vaccinology, infectious disease, autoimmunity, and cancer. The increasingly wide application of AIRR-seq is leading to a critical mass of studies being deposited in the public domain, offering the possibility of novel scientific insights through secondary analyses and meta-analyses. However, effective sharing of these large-scale data remains a challenge. The AIRR community has proposed minimal information about adaptive immune receptor repertoire (MiAIRR), a standard for reporting AIRR-seq studies. The MiAIRR standard has been operationalized using the National Center for Biotechnology Information (NCBI) repositories. Submissions of AIRR-seq data to the NCBI repositories typically use a combination of web-based and flat-file templates and include only a minimal amount of terminology validation. As a result, AIRR-seq studies at the NCBI are often described using inconsistent terminologies, limiting scientists’ ability to access, find, interoperate, and reuse the data sets. In order to improve metadata quality and ease submission of AIRR-seq studies to the NCBI, we have leveraged the software framework developed by the Center for Expanded Data Annotation and Retrieval (CEDAR), which develops technologies involving the use of data standards and ontologies to improve metadata quality. The resulting CEDAR-AIRR (CAIRR) pipeline enables data submitters to: (i) create web-based templates whose entries are controlled by ontology terms, (ii) generate and validate metadata, and (iii) submit the ontology-linked metadata and sequence files (FASTQ) to the NCBI BioProject, BioSample, and Sequence Read Archive databases. Overall, CAIRR provides a web-based metadata submission interface that supports compliance with the MiAIRR standard. This pipeline is available at , and will facilitate the NCBI submission process and improve the metadata quality of AIRR-seq studies.

Recent progress in the analysis of αβ T cell and B cell receptor repertoires

“…New analysis algorithms have been developed to address the wealth of new data, with tradeoffs between their ability to handle very large datasets, their sophistication of modeling the structure of Ig germline genes and rearrangements, and their applicability to single-cell data [37,[41][42][43][44][45]. Equally important are new initiatives formulating data standards, data structures and mechanisms to improve quality assurance and the ability to share and reanalyze Ig sequence data [46][47][48]. In parallel with the genetic tools, improved protein fragment analysis using mass spectrometry has enabled comparison of serum antibody proteins and BCR gene sequences in an individual, to characterize dominant clones in influenza vaccine responses [49,50].…”

AIRR Community Standardized Representations for Annotated Immune Repertoires

“…A major goal of the AIRR Community is to facilitate comparative and integrative analyses of AIRR data. So far, the community effort has defined a list of minimal metadata elements (MiAIRR) for describing published AIRR-seq datasets ( 2 ) and is actively developing simple interfaces for depositing these datasets in established repositories ( 3 ). As a first step toward standardization, the MiAIRR data standard focuses primarily on metadata describing the study design and the type of information to be collected.…”

Network organization of antibody interactions in sequence and structure space: the RADARS model

“…While this approach may be useful for classification, the use of the complete VDJ-H sequence as a first stage classifier, followed by VJ-L use better reflects the natural development scheme of B cells ( Fig 1C). Antibody repertoire sequencing now follows guidelines to help the integration of data (35)(36)(37), several tools and databases devoted especially for these data have been established (8,10,(38)(39)(40).…”