Targeted single-cell transcriptome readouts for high-throughput genetics and functional genomics

We show that targeted single-cell RNA-sequencing (TAP-seq) permits reliable mapping of cell (sub)types with as little as 100 reads per cell and reduces the sequencing costs for differential expression testing by a factor of 10-30, thereby enabling a cost-effective profiling of a large number of genotypes at the single cell level. We demonstrate the use of TAP-seq by generating comprehensive perturbation-based enhancer-target gene maps for 1.5% of the human genome. The performance of targeted single-cell RNA-seq (TAP) was compared to whole transcriptome seq (WTX) in various scenarios (for detail, refer to sample description): - TAP_DEEP: Comparison of targeting panels, targeted seq (deeply sequenced) - WTX_REF: Unperturbed K562 reference, whole Tx - TAP_CT: Cell type mapping (mouse bone marrow panel), targeted seq. - WTX_CT: Cell type mapping, whole Tx - see series GSE122465 - TAP_DIFFEX: Dataset for evaluation of differential expression, targeted seq. - WTX_DIFFEX: Dataset for evaluation of differential expression, whole tx. - TAP_SCREEN: Enhancer screen on chromosome 8 and 11, targeted seq. Additional datasets (supplement only): - TAP_TAR: Initial test experiments - TAP_REDESIGN: Redesign of Targeting panel 2