Beyond Bulk Single-chain Sequencing – Getting at the Whole Receptor

Curtis, Nicholas C.; Lee, Jiwon

Recent advancements in paired B cell receptor (BCR) sequencing technologies have accelerated the development of simpler, higher-throughput pipelines for generating native antibody heavy and light chain pairs used to elucidate novel antibodies and provide insights into antibody response against pathogenic targets. These technologies involve single-cell isolation, using either single wells or emulsified droplets to maintain physical separation of individual cells, followed by sequencing. The development of novel single well and emulsion-based workflows address key challenges by improving throughput of single-cell analyses, reducing method complexity, and integrating functional assays into existing workflows. Enabled by paired BCR sequencing, functional characterization of pathogen-specific antibodies reveals immunological insights beyond bulk sequencing.