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Penn Bioinformatics Forum – Cole Trapnell, PhD
April 10 @ 3:00 pm - 4:30 pm
Cole Trapnell, Ph.D.
Assistant Professor of Genome Sciences
University of Washington
Massively multiplex chemical transcriptomics at single cell resolution
High-throughput screens of bioactive compound libraries typically employ low-content assays, e.g. cell survival, which sharply limits what can be learned about mechanisms of action and off-target effects, and furthermore obscures heterogeneity in the responses of individual cells. Here we introduce sci-Chem, a method that employs “oligo hashing” to capture the global transcriptional responses of cells to a large number of chemical perturbations at single cell resolution. As a proof-of-concept, we apply sci-Chem to quantify the responses of 3 cancer cell lines to each of 188 compounds at 4 doses in duplicate, collectively profiling 574,457 single cell transcriptomes across 4,992 chemical perturbations in a single experiment. Our results reveal unexpected cellular heterogeneity in response to specific compounds, commonalities in the global transcriptional response to families of compounds, and insights into the unique properties of specific compounds within such families