Integrative single cell transcriptomics and functional profiling with TRAPS-seq and PAINTKiller-seq

Single-cell transcriptomics have significantly advanced our understanding of molecular cell subtypes. However, the correlation between cell types and their intrinsic functions remain elusive. We present two novel methods that can allow simultaneous functional and molecular profiling of single cells compatible with high throughput single-cell analysis platforms. Firstly, TRAPS-seq utilize a cell-surface affinity matrix to immobilize secreted proteins onto the source cell surface. Proteins secreted by cells over consecutive time windows are quantified using different feature barcoding antibodies, to establish the correlation between protein secretion dynamics, surface protein expression and transcriptome from single cells. Secondly, PAINTKiller-seq utilize a cell-surface affinity matrix to immobilize intracellular proteins. Cytotoxic cells that are “painted” by intracellular proteins from lysed target cells at close proximity and identified with feature barcoding antibodies. These approaches that combines functional readout with single cell transcriptomic measurements will be an important toolkit for understanding the molecular determinants of cellular functions.