Quantification of single-cell proteins, protein complexes and mRNA by proximity-sequencing

Description:
I will describe a new single cell proteomics technology, called proximity sequencing (Prox-seq), which enables simultaneous measurement of proteins, protein complexes and mRNA in thousands of individual cells. Prox-seq combines proximity ligation assay with microfluidic single-cell sequencing to measure proteins and their complexes from all pairwise combinations of targeted proteins, providing quadratically-scaled multiplexing. We studied human peripheral blood mononuclear cells using Prox-seq, identified various cell types using protein readouts, and discovered that naïve CD8 T cells display the protein complex CD8:CD9. We also study protein interactions during toll-like receptor (TLR) signaling in macrophages. We observe the formation and dissociation of signal-specific protein complexes and co-receptor activity, quantify signal integration under joint TLR4 and TLR2 stimulation, and show that quantification of protein complexes identifies signaling inputs received by single macrophages. Prox-seq provides access to an untapped measurement modality for single-cell phenotyping, is practical and broadly applicable, and can discover new protein interactions in different cell types.

Speaker: Savas Tay - University of Chicago
Savas Tay is a professor of Molecular Engineering at the University of Chicago. He is also a member of the Institute for Genomics and Systems Biology. Tay Laboratory develops single-cell and organoid analysis technologies, and applies them to study problems in immune signaling, infectious diseases and cancer.