In this GEN webinar, we discussed LIBRA-seq™, which determines antibody specificity using a next-generation sequencing-based readout. B cells are mixed with a panel of DNA-barcoded antigens, such that both the antigen barcode(s) and B-cell receptor (BCR) sequences of individual B cells are recovered via single-cell sequencing protocols, such as the 10x Genomics’ Single Cell V(D)J Solution. After first validating LIBRA-seq on B cell lines expressing known BCRs, we used this technology to screen B cells from human HIV-infection samples against large libraries of viral antigens and identified diverse panels of antibodies, including new broadly neutralizing antibodies. We expect the ability to interrogate antibody-antigen interactions using a sequencing-based readout to be indispensable to the fields of immune profiling and antibody discovery.