AIRRscape: An interactive tool for exploring B-cell receptor repertoires and antibody responses

• Published in: PLoS computational biology Vol. 18; no. 9; p. e1010052
• Main Authors: Waltari, Eric, Nafees, Saba, McCutcheon, Krista M, Wong, Joan, Pak, John E
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 20.09.2022; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Amino acids; B cells; B-cell receptor; Biology and Life Sciences; Complementarity-determining region 3; Computer and Information Sciences; Convergence; Coronaviruses; COVID-19 vaccines; Datasets; Dengue; Dengue fever; DNA sequencing; Genetic aspects; HIV; Human immunodeficiency virus; Humoral immunity; Immunity; Infections; Light chains; Lymphocytes B; Medicine and Health Sciences; Monoclonal antibodies; Network topologies; Nucleotide sequencing; Pathogens; Patients; Receptors; Research and Analysis Methods; Severe acute respiratory syndrome coronavirus 2; Vaccines; Vector-borne diseases; Viral diseases; Viral infections; Viruses; Visualization; Web browsers; United States
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1010052

The sequencing of antibody repertoires of B-cells at increasing coverage and depth has led to the identification of vast numbers of immunoglobulin heavy and light chains. However, the size and complexity of these Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) datasets makes it difficult to perform exploratory analyses. To aid in data exploration, we have developed AIRRscape, an R Shiny-based interactive web browser application that enables B-cell receptor (BCR) and antibody feature discovery through comparisons among multiple repertoires. Using AIRR-seq data as input, AIRRscape starts by aggregating and sorting repertoires into interactive and explorable bins of germline V-gene, germline J-gene, and CDR3 length, providing a high-level view of the entire repertoire. Interesting subsets of repertoires can be quickly identified and selected, and then network topologies of CDR3 motifs can be generated for further exploration. Here we demonstrate AIRRscape using patient BCR repertoires and sequences of published monoclonal antibodies to investigate patterns of humoral immunity to three viral pathogens: SARS-CoV-2, HIV-1, and DENV (dengue virus). AIRRscape reveals convergent antibody sequences among datasets for all three pathogens, although HIV-1 antibody datasets display limited convergence and idiosyncratic responses. We have made AIRRscape available as a web-based Shiny application, along with code on GitHub to encourage its open development and use by immuno-informaticians, virologists, immunologists, vaccine developers, and other scientists that are interested in exploring and comparing multiple immune receptor repertoires.