SONAR: A High-Throughput Pipeline for Inferring Antibody Ontogenies from Longitudinal Sequencing of B Cell Transcripts

Chaim A. Schramm, Zizhang Sheng, Zhenhai Zhang, John R. Mascola, Peter D. Kwong, Lawrence Shapiro

The rapid advance of massively parallel or next-generation sequencing technologies has made possible the characterization of B cell receptor repertoires in ever greater detail, and these developments have triggered a proliferation of software tools for processing and annotating these data. Of especial interest, however, is the capability to track the development of specific antibody lineages across time, which remains beyond the scope of most current programs. We have previously reported on the use of techniques such as inter- and intradonor analysis and CDR3 tracing to identify transcripts related to an antibody of interest. Here, we present Software for the Ontogenic aNalysis of Antibody Repertoires (SONAR), capable of automating both general repertoire analysis and specialized techniques for investigating specific lineages. SONAR annotates next-generation sequencing data, identifies transcripts in a lineage of interest, and tracks lineage development across multiple time points. SONAR also generates figures, such as identity-divergence plots and longitudinal phylogenetic "birthday" trees, and provides interfaces to other programs such as DNAML and BEAST. SONAR can be downloaded as a ready-to-run Docker image or manually installed on a local machine. In the latter case, it can also be configured to take advantage of a high-performance computing cluster for the most computationally intensive steps, if available. In summary, this software provides a useful new tool for the processing of large next-generation sequencing datasets and the ontogenic analysis of neutralizing antibody lineages. SONAR can be found at https://github.com/scharch/SONAR, and the Docker image can be obtained from https://hub.docker.com/r/scharch/sonar/.