Data from: Droplet-based single-cell pairing for high-throughput interaction mapping of antigen-receptor combinations

Mapping the interaction potential of different variant combinations of
viral antigens and human cell receptors and understanding how viral
antigen mutations interact with human genetic polymorphisms are critical
for predicting infection susceptibility and informing precision public
health strategies. Here, we develop a droplet-based single-cell pairing
and library-on-library interaction screening (SPLIS) system for
high-throughput profiling of the syncytium-formation landscapes of various
spike-angiotensin-converting enzyme 2 (ACE2) variant combinations. This
system uses combined droplet sorting and merging to deterministically
encapsulate one antigen-presenting sender cell and one receptor-expressing
receiver cell into each drop, followed by selection and sequencing of the
fused DNA readouts to characterize the syncytium-formation potential of
each combination. We applied SPLIS to characterize both fusion-enhancing
and -inhibiting variant pairs, comprehensively profiling how ACE2
single-nucleotide polymorphisms (SNPs) modulate susceptibility to emerging
SARS-CoV-2 spike mutations. Our system emerges as a powerful tool to
interrogate the interactions between two libraries of variants, offering
valuable insights into host susceptibility patterns and viral infectivity
trends.