Table 1.

Single-cell perturbation screens. Each method includes a description of the modalities captured, the CRISPR gRNA or perturbation capture method, the types of pooled screens they enable, and the single-cell partitioning and chemistry.

Single-cell perturbation screen method	Modalities captured	Guide RNA or perturbation capture	Pooled perturbations	Single-cell capture and chemistry	Reference
ECCITE-seq	Transcriptome and cell surface markers	Does not require a specialized gRNA plasmid. Requires a direct capture spike-in oligo.	CRISPR Cas9-based screens (e.g. gene knockout, activation, inhibition, base editing).	Droplet-based single-cell experiments relying on 5’ capture of transcripts.	40
CROP-seq	Transcriptome	Requires a specialized CROP-seq plasmid to capture poly-adenylated gRNA barcodes.	CRISPR Cas9-based screens (e.g. gene knockout, activation, inhibition, base editing).	Combinatorial indexing and droplet-based single-cell experiments relying on 3’ poly-A tail capture.	39
Direct Perturb-seq / Perturb-CITE-seq	Transcriptome and cell surface markers*	Requires specialized gRNA plasmids with encoded capture sequences. Requires a direct capture spike-in oligo.	CRISPR Cas9-based screens (e.g. gene knockout, activation, inhibition, base editing).	Droplet-based single-cell experiments relying on 3’ or 5’ capture of transcripts.	41, 62
TAP-seq	Select transcripts	Can be coupled with gRNA capture method of choice.	Can be coupled with CRISPR screening method of choice. Requires nested primers designed to enrich single-cell sequencing libraries for transcripts of choice.	Droplet-based single-cell experiments relying on 3’ or 5’ capture of transcripts.	52
CaRPool-seq	Transcriptome and cell surface markers	Requires specialized gRNA plasmids with encoded capture sequences in a cleavable gRNA array.	CRISPR Cas13-based screens (e.g. RNA knockout, inhibition, base editing).	Droplet-based single-cell experiments relying on 3’ capture of transcripts.	103
OverCITE-seq	Transcriptome and open reading frames**	Requires a direct capture spike-in oligo to capture open reading frames.	Alternate screening approach for CRISPR activation.	Droplet-based single-cell experiments relying on 5’ capture of transcripts.	104
CRISPR-sciATAC	Open chromatin	Does not require a specialized gRNA plasmid. Requires tagging integrated gRNAs with reverse transcription and PCR.	CRISPR Cas9-based screens (e.g. gene knockout, activation, inhibition, base editing).	Combinatorial indexing-based single-cell experiments relying on DNA tagmentation.	47
Perturb-ATAC	Open chromatin	Does not require a specialized gRNA plasmid. Requires a direct capture spike-in oligo.	Cas9-based screens (e.g. gene knockout, activation, inhibition, base editing).	Physically isolated single cells relying on DNA tagmentation.	70
Spear-ATAC	Open chromatin	Requires a specialized gRNA plasmid with Nextera read adapters flanking the gRNA and a direct capture spike-in oligo.	CRISPR Cas9-based screens (e.g. gene knockout, activation, inhibition, base editing).	Droplet-based single-cell experiments relying on DNA tagmentation.	71

^*Direct Perturb-seq captures the transcriptome only, Perturb-CITE-seq captures both transcriptome and cell surface markers

^**Uses lentivirally transduced open-reading frames as an alternative to CRISPR activation screening